Simponi

Golimumab.

Pre‑Filled Pen/autoinjector (SmartJect): One 0.5 mL pre-filled pen/autoinjector (SmartJect) contains 50 mg of golimumab.
Golimumab is a human IgG1қ monoclonal antibody produced by a murine hybridoma cell line with recombinant DNA technology.
Excipients/Inactive Ingredients: The excipients are sorbitol (E420), L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80 and water for injection.

Tumour necrosis factor alpha (TNF-α) inhibitor.
Pharmacology: Pharmacodynamics: Mechanism of action: Golimumab is a human monoclonal antibody that forms high affinity, stable complexes with both the soluble and transmembrane bioactive forms of human TNF-α, which prevents the binding of TNF-α to its receptors.
Pharmacodynamic effects: The binding of human TNF by golimumab was shown to neutralize TNF-α-induced cell-surface expression of the adhesion molecules E-selectin, vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 by human endothelial cells. In vitro, TNF-induced secretion of interleukin (IL)-6, IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by human endothelial cells was also inhibited by golimumab.
Improvement in C-reactive protein (CRP) levels were observed relative to placebo groups and treatment with Golimumab (Simponi) resulted in significant reductions from baseline in serum levels of IL-6, ICAM-1, matrix-metalloproteinase (MMP)-3 and vascular endothelial growth factor (VEGF) compared to control treatment. In addition, levels of TNF-α were reduced in RA and AS patients and levels of IL-8 were reduced in PsA patients. These changes were observed at the first assessment (week 4) after the initial Golimumab (Simponi) administration and were generally maintained through week 24.
Clinical efficacy: Rheumatoid arthritis: The efficacy of Golimumab (Simponi) was demonstrated in three multi-center, randomized, double-blind, placebo-controlled studies in over 1500 patients ≥18 years of age with moderately to severely active RA, diagnosed according to the American College of Rheumatology (ACR) criteria for at least 3 months prior to screening. Patients had at least 4 swollen and 4 tender joints. Golimumab (Simponi) or placebo were subcutaneously administered every 4 weeks.
GO-FORWARD evaluated 444 patients who had active RA despite a stable dose of at least 15 mg/week of MTX and who had not been previously treated with an anti-TNF agent. Patients were randomized to receive placebo + MTX, Golimumab (Simponi) 50 mg + MTX, Golimumab (Simponi) 100 mg + MTX or Golimumab (Simponi) 100 mg + placebo. Patients receiving placebo + MTX were switched to Golimumab (Simponi) 50 mg + MTX after Week 24. At Week 52, patients entered an open-label long-term extension.
GO-AFTER evaluated 445 patients who were previously treated with one or more of the anti-TNF agents adalimumab, etanercept, or infliximab. Patients were randomized to receive placebo, Golimumab (Simponi) 50 mg, or Golimumab (Simponi) 100 mg. Patients were allowed to continue concomitant DMARD therapy with MTX, sulfasalazine (SSZ), and/or hydroxychloroquine (HCQ) during the study. The stated reasons for discontinuation of prior anti-TNF therapies were lack of efficacy (58%), intolerance (13%), and/or reasons other than safety or efficacy (29%, mostly for financial reasons).
GO-BEFORE evaluated 637 patients with active RA who were MTX-naïve and had not previously been treated with an anti-TNF agents. Patients were randomized to receive placebo + MTX, Golimumab (Simponi) 50 mg + MTX, Golimumab (Simponi) 100 mg + MTX or Golimumab (Simponi) 100 mg + placebo. At week 52, patients entered an open-label, long-term extension in which patients receiving placebo + MTX who had at least 1 tender or swollen joint were switched to Simponi 50 mg + MTX.
In GO-FORWARD, the (co-)primary endpoints were the percentage of patients achieving an ACR 20 response at Week 14 and the improvement from baseline in Health Assessment Questionnaire (HAQ) at Week 24. In GO-AFTER, the primary endpoint was the percentage of patients achieving an ACR 20 response at Week 14. In GO-BEFORE, the co-primary endpoints were the percentage of patients achieving ACR 50 response at Week 24 and the change from baseline in the van der Heijde-modified Sharp (vdH-S) score at Week 52. In addition to the primary endpoint(s), additional assessments of the impact of Golimumab (Simponi) treatment on the signs and symptoms of arthritis, radiographic response, physical function, and health-related quality of life were performed.
In general, no clinically meaningful differences in measures of efficacy were observed between the Golimumab (Simponi) 50 and 100 mg dosing regimens with concomitant MTX, through week 104 in GO-FORWARD and GO-BEFORE and through week 24 in GO-AFTER. In each of the RA studies by study design, patients in the long-term extension may have switched between the 50 mg and 100 mg Golimumab (Simponi) doses at the discretion of the study physician.
Signs and symptoms: Key ACR results for the Golimumab (Simponi) 50-mg dose at weeks 14, 24, and 52 for GO-FORWARD, GO-AFTER, and GO-BEFORE are shown in Table 1 and are described as follows.
Responses were observed at the first assessment (Week 4) after the initial Golimumab (Simponi) administration.
In GO-FORWARD, among 89 patients randomized to Golimumab (Simponi) 50 mg + MTX, 48 were still on this treatment at week 104. Among those, 40, 33 and 24 patients had ACR 20/50/70 response, respectively at week 104. Among patients remaining in the study and treated with Golimumab (Simponi), similar rates of ACR 20/50/70 response was observed from week 104 through week 256.
In GO-AFTER, the percentage of patients achieving an ACR 20 response was greater for patients receiving Golimumab (Simponi) than for patients receiving placebo regardless of the reason reported for discontinuation of one or more prior anti-TNF therapies. (See Table 1.)

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In GO-BEFORE the primary analysis in patients with moderate to severe rheumatoid arthritis (combined Golimumab (Simponi) 50 mg and 100 mg + MTX groups vs MTX alone for ACR 50) was not statistically significant at week 24 (p=0.053). At week 52 in the overall population, the percentage of patients in the Golimumab (Simponi) 50 mg + MTX group who achieved an ACR response was generally higher but not significantly different when compared with MTX alone (see Table 1). Additional analyses were performed in subsets representative of the indicated population of patients with severe, active and progressive RA. A generally greater effect of Golimumab (Simponi) 50 mg + MTX versus MTX alone was demonstrated in the indicated population compared with the overall population.
In GO‑FORWARD and GO‑AFTER, clinically meaningful and statistically significant responses in Disease Activity Scale (DAS)28 were observed at each prespecified timepoint, at week 14 and at week 24 (p≤0.001). Among patients who remained on the Golimumab (Simponi) treatment to which they were randomized at study start, DAS28 responses were maintained through week 104. Among patients remaining in the study and treated with Golimumab (Simponi), DAS28 responses were similar from week 104 through week 256.
In GO‑BEFORE, major clinical response, defined as the maintenance of an ACR 70 response over a continuous 6‑month period, was measured. At week 52, 15% of patients in the Golimumab (Simponi) 50 mg + MTX group achieved a major clinical response compared with 7% of patients in the placebo + MTX group (p=0.018). Among 159 patients randomized to Golimumab (Simponi) 50 mg + MTX, 96 were still on this treatment at week 104. Among patients remaining in the study and treated with Golimumab (Simponi), similar rates of ACR 20/50/70 response were observed from week 104 through week 256.
Radiographic response: In GO‑BEFORE, the change from baseline in the vdH‑S score, a composite score of structural damage that radiographically measures the number and size of joint erosions and the degree of joint space narrowing in hands/wrists and feet, was used to assess the degree of structural damage. Key results for the Golimumab (Simponi) 50‑mg dose at Week 52 are presented in Table 2.
The number of patients with no new erosions or a change from baseline in total vdH‑S Score ≤ 0 was significantly higher in the Golimumab (Simponi) treatment group than in the control group (p=0.003). The radiographic effects observed at week 52 were maintained through week 104. Among patients remaining in the study and treated with Golimumab (Simponi), radiographic effects were similar from week 104 through week 256. (See Table 2.)

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Physical function and health‑related quality of life: Physical function and disability were assessed as a separate endpoint in GO‑FORWARD and GO‑AFTER using the disability index of the HAQ DI. In these studies, Golimumab (Simponi) demonstrated clinically meaningful and statistically significant improvement in HAQ DI from baseline versus control at week 24. Among patients who remained on the Golimumab (Simponi) treatment to which they were randomized at study start, improvement in HAQ DI was maintained through week 104. Among patients remaining in the study and treated with Golimumab (Simponi), improvement in HAQ DI was similar from week 104 through week 256.
In GO‑FORWARD clinically meaningful and statistically significant improvements were demonstrated in health‑related quality of life as measured by the physical component score of the SF‑36 in patients treated with Golimumab (Simponi) versus placebo at week 24. Among patients who remained on the Golimumab (Simponi) treatment to which they were randomized at study start, improvement of the SF‑36 physical component was maintained through week 104 through week 256. In GO‑FORWARD and GO‑AFTER, statistically significant improvements were observed in fatigue as measured by functional assessment of chronic illness therapy‑fatigue scale (FACIT‑F).
Psoriatic arthritis: The safety and efficacy of Golimumab (Simponi) were evaluated in a multi‑center, randomized, double‑blind, placebo‑controlled study (GO‑REVEAL) in 405 adult patients with active PsA (≥ 3 swollen joints and ≥ 3 tender joints) despite non‑steroidal anti‑inflammatory (NSAID) or DMARD therapy. Patients in this study had a diagnosis of PsA for at least 6 months and had at least mild psoriatic disease. Patients with each sub‑type of psoriatic arthritis were enrolled, including polyarticular arthritis with no rheumatoid nodules (43%), asymmetric peripheral arthritis (30%), distal interphalangeal (DIP) joint arthritis (15%), spondylitis with peripheral arthritis (11%), and arthritis mutilans (1%). Previous treatment with an anti‑TNF agent was not allowed. Golimumab (Simponi) or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo, Golimumab (Simponi) 50 mg, or Golimumab (Simponi) 100 mg. Patients receiving placebo were switched to Golimumab (Simponi) 50 mg after week 24. Patients entered an open-label, long‑term extension at week 52. Approximately forty‑eight percent of patients continued on stable doses of methotrexate (≤ 25 mg/week). The co‑primary endpoints were the percentage of patients achieving ACR 20 response at week 14 and change from baseline in total PsA modified vdH‑S score at week 24.
In general, no clinically meaningful differences in measures of efficacy were observed between the Golimumab (Simponi) 50 mg and 100 mg dosing regimens through week 104. By study design, patients in the long‑term extension may have switched between the 50 mg and 100 mg Golimumab (Simponi) doses at the discretion of the study physician.
Signs and symptoms: Key results for the 50 mg dose at weeks 14 and 24 are shown in Table 3 and described as follows. (See Table 3).

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Responses were observed at the first assessment (Week 4) after the initial Golimumab (Simponi) administration. Similar ACR 20 responses at Week 14 were observed in patients with polyarticular arthritis with no rheumatoid nodules and asymmetric peripheral arthritis PsA subtypes. The number of patients with other PsA subtypes was too small to allow meaningful assessment. Responses observed in the Golimumab (Simponi)‑treated groups were similar in patients receiving and not receiving concomitant MTX. Among 146 patients randomized to Golimumab (Simponi) 50 mg, 70 were still on this treatment at week 104. Of these 70 patients, 64, 46, and 31 patients had an ACR 20/50/70 response, respectively. Among patients remaining in the study and treated with Golimumab (Simponi), similar rates of ACR 20/50/70 response was observed from week 104 through week 256.
Statistically significant responses in DAS28 were also observed at weeks 14 and 24 (p<0.05).
At week 24 improvements in parameters of peripheral activity characteristic of psoriatic arthritis (e.g. number of swollen joints, number of painful/tender joints, dactylitis and enthesitis) were seen in the Golimumab (Simponi)‑treated patients. Golimumab (Simponi) treatment resulted in significant improvement in physical function as assessed by HAQ DI, as well as significant improvements in health‑related quality of life as measured by the physical and mental component summary scores of the SF‑36. Among patients who remained on the Golimumab (Simponi) treatment to which they were randomized at study start, DAS28 and HAQ DI responses were maintained through week 104. Among patients remaining in the study and treated with Golimumab (Simponi), DAS28 and HAQ DI responses were similar from week 104 through week 256.
Radiographic response: Structural damage in both hands and feet was assessed radiographically by the change from baseline in the vdH‑S score, modified for PsA by addition of hand distal interphalangeal (DIP) joints.
Golimumab (Simponi) 50‑mg treatment reduced the rate of progression of peripheral joint damage compared with placebo treatment at week 24 as measured by change from baseline in total modified vdH‑S Score (mean ± SD score was 0.27 ± 1.3 in the placebo group compared with ‑0.16 ±1.3 in the Golimumab (Simponi) group; p=0.011). Out of 146 patients who were randomized to Golimumab (Simponi) 50 mg, 52‑week X‑ray data were available for 126 patients, of whom 77% showed no progression compared to baseline. At week 104, X‑ray data were available for 114 patients, and 77% showed no progression from baseline. Among patients remaining in the study and treated with Golimumab (Simponi), similar rates of patients showed no progression from baseline from week 104 through week 256.
Axial spondyloarthritis: Ankylosing spondylitis: The safety and efficacy of Golimumab (Simponi) were evaluated in a multi‑center, randomized, double‑blind, placebo‑controlled study (GO‑RAISE) in 356 adult patients with active ankylosing spondylitis (defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and a VAS for total back pain of ≥ 4, on a scale of 0 to 10 cm). Patients enrolled in this study had active disease despite current or previous NSAID or DMARD therapy and had not previously been treated with anti‑TNF therapy. Golimumab (Simponi) or placebo were administered subcutaneously every 4 weeks. Patients were randomly assigned to placebo, Golimumab (Simponi) 50 mg, and Golimumab (Simponi) 100 mg and were allowed to continue concomitant DMARD therapy (MTX, SSZ, and/or HCQ). The primary endpoint was the percentage of patients achieving Ankylosing Spondylitis Assessment Study Group (ASAS) 20 response at week 14. Placebo‑controlled efficacy data were collected and analyzed through week 24.
Key results for the 50 mg dose are shown in Table 4 and described as follows. In general, no clinically meaningful differences in measures of efficacy were observed between the Golimumab (Simponi) 50 mg and 100 mg dosing regimens through week 24. By study design, patients in the long-term extension may have switched between the 50 mg and 100 mg Golimumab (Simponi) doses at the discretion of the study physician. (See Table 4.)

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Among patients remaining in the study and treated with Golimumab (Simponi), the proportion of patients with an ASAS 20 and ASAS 40 response were similar from week 24 through week 256.
Statistically significant responses in BASDAI 50, 70 and 90 (p≤0.017) were also seen at weeks 14 and 24. Improvements in key measures of disease activity were observed at the first assessment (week 4) after the initial Golimumab (Simponi) administration and were maintained through week 24. Among patients remaining in the study and treated with Golimumab (Simponi), similar rates of change from baseline in BASDAI were observed from week 24 through week 256. Consistent efficacy was seen in patients regardless of use of DMARDs (MTX, sulfasalazine, and/or hydroxychloroquine), HLA‑B27 antigen status, or baseline CRP levels as assessed by ASAS 20 responses at week 14.
Golimumab (Simponi) treatment resulted in significant improvements in physical function as assessed by changes from baseline in BASFI at weeks 14, 24. Health‑related quality of life as measured by the physical component score of the SF‑36 was also improved significantly at weeks 14 and 24. Among patients remaining in the study and treated with Golimumab (Simponi), improvements in physical function and health‑related quality of life were similar from week 24 through week 256.
Non-radiographic axial spondyloarthritis: The safety and efficacy of Golimumab (Simponi) were evaluated in a multi‑centre, randomised, double‑blind, placebo‑controlled study (GO‑AHEAD) in 197 adult patients with severe active nr‑Axial SpA (defined as those patients meeting the ASAS classification criteria of axial spondyloarthritis but did not meet the modified New York criteria for AS). Patients enrolled in this study had active disease (defined as a BASDAI ≥ 4 and a Visual Analogue Scale (VAS) for total back pain of ≥ 4, each on a scale of 0‑10 cm) despite current or previous NSAID therapy and had not previously been treated with any biological agents including anti‑TNF therapy. Patients were randomly assigned to placebo or Golimumab (Simponi) 50 mg administered subcutaneously every 4 weeks. At week 16, patients entered an open label period in which all patients received Golimumab (Simponi) 50 mg administered subcutaneously every 4 weeks through week 48 with efficacy assessments performed through week 52 and safety follow-up through week 60. Approximately 93% of patients who were receiving Golimumab (Simponi) at the beginning of the open-label extension (week 16) remained on treatment through the end of the study (week 52). Analyses were performed on both the All Treated (AT, N = 197) and Objective Signs of Inflammation (OSI, N = 158, defined by elevated CRP and/or evidence of sacroiliitis on MRI at baseline) populations. Placebo‑controlled efficacy data were collected and analyzed through week 16. The primary endpoint was the proportion of patients achieving ASAS 20 response at week 16. Key results are shown in Table 5 and described as follows.

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Statistically significant improvements in signs and symptoms of severe active nr‑Axial SpA were demonstrated in patients treated with Golimumab (Simponi) 50 mg compared to placebo at week 16 (Table 5). Improvements were observed at the first assessment (week 4) after the initial Golimumab (Simponi) administration. SPARCC score as measured by MRI showed statistically significant reductions in SI joint inflammation at week 16 in patients treated with Golimumab (Simponi) 50 mg compared to placebo (Table 5). Pain as assessed by the Total Back Pain and Nocturnal Back Pain VAS, and disease activity as measured by ASDAS‑C also showed statistically significant improvement from baseline to week 16 in patients treated with Golimumab (Simponi) 50 mg compared to placebo (p < 0.0001).
Statistically significant improvements in spinal mobility as assessed by BASMI (Bath Ankylosing Spondylitis Metrology Index) and in physical function as assessed by the BASFI were demonstrated in Golimumab (Simponi) 50 mg‑treated patients as compared to placebo‑treated patients (p < 0.0001). Patients treated with Golimumab (Simponi) experienced significantly more improvements in health‑related quality of life as assessed by ASQoL, EQ‑5D, and physical and mental components of SF‑36, and experienced significantly more improvements in productivity as assessed by greater reductions in overall work impairment and in activity impairment as assessed by the WPAI questionnaire than patients receiving placebo.
For all of the endpoints described as previously mentioned, statistically significant results were also demonstrated in the OSI population at week 16.
In both the AT and OSI populations, the improvements in signs and symptoms, spinal mobility, physical function, quality of life, and productivity observed at week 16 among patients treated with Golimumab (Simponi) 50 mg continued in those remaining in the study at week 52.
Ulcerative colitis: The efficacy of Golimumab (Simponi) was evaluated in two randomized, double‑blind, placebo‑controlled clinical studies in adult patients.
The induction study (PURSUIT‑Induction) evaluated patients with moderately to severely active ulcerative colitis (Mayo score 6 to 12; Endoscopy subscore ≥ 2) who had an inadequate response to or failed to tolerate conventional therapies, or were corticosteroid dependent. In the dose confirming portion of the study, efficacy was evaluated in 761 patients who were randomized to receive either 400 mg Golimumab (Simponi) SC at week 0 and 200 mg at week 2, 200 mg Golimumab (Simponi) SC at week 0 and 100 mg at week 2, or placebo SC at weeks 0 and 2. Concomitant stable doses of oral aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted. The efficacy of Golimumab (Simponi) through week 6 was assessed in this study.
The results of the maintenance study (PURSUIT‑Maintenance) were based on evaluation of 456 patients who achieved clinical response from previous induction with Golimumab (Simponi). Patients were randomized to receive Golimumab (Simponi) 50 mg, Golimumab (Simponi) 100 mg, or placebo administered subcutaneously every 4 weeks. Concomitant stable doses of oral aminosalicylates, and/or immunomodulatory agents were permitted. Corticosteroids were to be tapered at the start of the maintenance study. The efficacy of Golimumab (Simponi) through week 54 was assessed in this study. Patients who completed the maintenance study through week 54 continued treatment in a study extension, with efficacy evaluated through week 216. Efficacy evaluation in the study extension was based on changes in corticosteroid use, Physician's Global Assessment (PGA) of disease activity, and improvement in quality of life as measured by Inflammatory Bowel Disease Questionnaire (IBDQ). (See Table 6.)

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More Golimumab (Simponi)‑treated patients demonstrated sustained mucosal healing (patients with mucosal healing at both week 30 and week 54) in the 50‑mg group (42%, nominal p<0.05) and 100‑mg group (42%, p<0.005) compared with patients in the placebo group (27%).
Among the 54% of patients (247/456) who were receiving concomitant corticosteroids at the start of PURSUIT‑Maintenance, the proportion of patients who maintained clinical response through week 54 and were not receiving concomitant corticosteroids at week 54 was greater in the 50 mg group (38%, 30/78) and 100‑mg group (30%, 25/82) compared with the placebo group (21%, 18/87). The proportion of patients who eliminated corticosteroids by Week 54 was greater in the 50‑mg group (41%, 32/78) and 100‑mg group (33%, 27/82) compared with the placebo group (22%, 19/87). Among patients who entered the study extension, the proportion of subjects who remained corticosteroid-free was generally maintained through week 216.
Patients who did not achieve clinical response at week 6 in the PURSUIT-Induction studies were dosed Golimumab (Simponi) 100 mg every 4 weeks in the PURSUIT-Maintenance study. At week 14, 28% of these patients achieved response defined by partial Mayo score (decreased by ≥ 3 points compared with start of induction). At week 54, the clinical outcomes observed in these patients were similar to the clinical outcomes reported for the patients achieving clinical response at week 6.
At week 6, Golimumab (Simponi) significantly improved quality of life as measured by change from baseline in a disease specific measure, IBDQ (inflammatory bowel disease questionnaire). Among patients who received Golimumab (Simponi) maintenance treatment, the improvement in quality of life as measured by IBDQ was maintained through week 54.
Approximately 63% of patients, who were receiving Golimumab (Simponi) at the beginning of the study extension (week 56), remained on treatment through the end of the study (last golimumab administration at week 212).
Immunogenicity: Across the Phase III RA, PsA and AS studies through week 52, antibodies to golimumab were detected by the enzyme immunoassay (EIA) method in 5% (105/2062) of golimumab treated patients and, where tested, nearly all antibodies were neutralising in vitro. Similar rates were shown across rheumatologic indications. Treatment with concomitant MTX resulted in a lower proportion of patients with antibodies to golimumab than patients receiving golimumab without MTX (approximately 3% [41/1235] versus 8% [64/827], respectively).
In nr‑Axial SpA, antibodies to golimumab were detected in 7% (14/193) of golimumab treated patients through week 52 by the EIA method.
In the Phase II and III UC studies through week 54, antibodies to golimumab were detected by the EIA method in 3% (26/946) of golimumab treated patients. Sixty-eight percent (21/31) of antibody‑positive patients had neutralising antibodies in vitro. Treatment with concomitant immunomodulators (azathioprine, 6‑mercaptopurine and MTX) resulted in a lower proportion of patients with antibodies to golimumab than patients receiving golimumab without immunomodulators (1% (4/308) versus 3% (22/638), respectively). Of patients that continued in the study extension and had evaluable samples through week 228, antibodies to golimumab were detected in 4% (23/604) of golimumab treated patients. Eighty-two percent (18/22) of antibody-positive patients had neutralizing antibodies in vitro.
A drug‑tolerant EIA method was used in the pJIA study for the detection of antibodies to golimumab. Due to the higher sensitivity and the improved drug tolerance, a higher incidence of antibodies to golimumab was expected to be detected with the drug‑tolerant EIA method compared to the EIA method. In the Phase III pJIA study through week 48, antibodies to golimumab were detected by the drug‑tolerant EIA method in 40% (69/172) of golimumab treated children of which a majority had a titre lower than 1:1000. An effect on serum golimumab concentrations was seen at titres of > 1:100 while an effect on efficacy was not seen until titres of > 1:1000, though the numbers of children with titres of > 1:1000 were low (N = 8). Among the children who tested positive for antibodies to golimumab, 39% (25/65) had neutralising antibodies. The higher incidence of antibodies with the drug‑tolerant EIA method, because they were mainly low titre antibodies, did not have an apparent impact on drug levels, efficacy and safety and therefore does not represent any new safety signal.
The presence of antibodies to golimumab may increase the risk of injection site reactions. The small number of patients positive for antibodies to golimumab limits the ability to draw definitive conclusions regarding the relationship between antibodies to golimumab and clinical efficacy or safety measures.
Because immunogenicity analyses are product‑ and assay‑specific, comparison of antibody rates with those from other products is not appropriate.
Pediatric population: Polyarticular juvenile idiopathic arthritis: The safety and efficacy of Golimumab (Simponi) was evaluated in a randomised, double-blind, placebo‑controlled, withdrawal study (GO-KIDS) in 173 children (2 to 17 years of age) with active pJIA with at least 5 active joints and an inadequate response to MTX. Children with polyarticular course JIA (rheumatoid factor positive or negative polyarthritis, extended oligoarthritis, juvenile psoriatic arthritis or systemic JIA with no current systemic symptoms) were included in the study. The baseline median number of active joints was 12, and median CRP was 0.17 mg/dL.
Part 1 of the study consisted of a 16‑week open/autoinjector (SmartJect)‑label phase in which 173 enrolled children received Golimumab (Simponi) 30 mg/m² (maximum 50 mg) subcutaneously every 4 weeks and MTX. The 154 children who achieved an ACR Ped 30 response at week 16 entered Part 2 of the study, the randomised withdrawal phase, and received Golimumab (Simponi) 30 mg/m² (maximum 50 mg) + MTX or placebo + MTX every 4 weeks. After disease flare, children received Golimumab (Simponi) 30 mg/m² (maximum 50 mg) + MTX. At week 48, children entered a long‑term extension.
Children in this study demonstrated ACR Ped 30, 50, 70, and 90 responses as early as week 4.
At week 16, 87% of children were ACR Ped 30 responders, and 79%, 66%, and 36% of children were ACR Ped 50, ACR Ped 70, and ACR Ped 90 responders, respectively. At week 16, 34% of children had inactive disease defined as having the presence of all of the following: no joints with active arthritis; no fever, rash, serositis, splenomegaly, hepatomegaly, or generalised lymphadenopathy attributable to JIA; no active uveitis; normal ESR (< 20 mm/hour) or CRP (< 1.0 mg/dL); physician global assessment of disease activity (≤ 5 mm on the VAS); duration of morning stiffness < 15 minutes.
At week 16, all ACR Ped components demonstrated clinically relevant improvement from baseline (see Table 7).

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The primary endpoint, the proportion of children who were ACR Ped 30 responders at week 16 and who did not experience a flare between week 16 and week 48, was not achieved. The majority of children did not experience a flare between week 16 and week 48 (59% in the Golimumab (Simponi) + MTX and 53% in the placebo + MTX groups, respectively; p = 0.41).
Pre-specified subgroup analyses of the primary endpoint by baseline CRP (≥ 1 mg/dL vs < 1 mg/dL) demonstrated higher flare rates in placebo + MTX vs Golimumab (Simponi) + MTX treated subjects among subjects with baseline CRP ≥ 1 mg/dL (87% vs 40% p = 0.0068).
At week 48, 53% and 55% of children in the Golimumab (Simponi) + MTX group and placebo + MTX group, respectively, were ACR Ped 30 responders, and 40% and 28% of children in the Golimumab (Simponi) + MTX group and placebo + MTX group, respectively, achieved inactive disease.
Pharmacokinetics: Absorption: Following a single subcutaneous administration of golimumab to healthy subjects or patients with RA, the time to reach maximum serum concentrations (T_max) ranged from 2 to 6 days. A subcutaneous injection of 50 mg golimumab to healthy subjects produced a mean ± standard deviation maximum serum concentration (C_max) of 3.2 ± 1.4 μg/mL.
Following a single subcutaneous injection of 100 mg, the absorption of golimumab was similar in the upper arm, abdomen, and thigh, with a mean absolute bioavailability of 51%. Since golimumab exhibited approximately dose proportional PK following a SC administration, the absolute bioavailability of a golimumab 50 mg or 200 mg dose is expected to be similar.
Distribution: Following a single IV administration, the mean volume of distribution was 115 ± 19 mL/kg.
Elimination: The systemic clearance of golimumab was estimated to be 6.9 ± 2.0 mL/day/kg. Terminal half‑life value was estimated to be approximately 12 ± 3 days in healthy subjects and similar values were observed in patients with RA, PsA, AS, or UC.
When 50 mg Golimumab (Simponi) was administered subcutaneously to patients with RA, PsA, or AS every 4 weeks, serum concentrations reached steady state by week 12. With concomitant use of MTX, treatment with 50 mg golimumab subcutaneous every 4 weeks resulted in a mean (± standard deviation) steady‑state trough serum concentration of approximately 0.6 ± 0.4 mg/mL in RA patients with active RA despite MTX therapy, and approximately 0.5 ± 0.4 mg/mL in patients with active PsA and approximately 0.8 ± 0.4 mcg/mL in patients with AS. Steady‑state mean trough serum golimumab concentrations in patients with nr‑Axial SpA were similar to those observed in patients with AS following subcutaneous administration of 50 mg golimumab every 4 weeks.
Patients with RA, PsA, or AS who did not receive concomitant MTX had approximately 30% lower steady‑state trough concentrations of golimumab than those who received golimumab with MTX. In a limited number of RA patients treated with subcutaneous golimumab over a 6‑month period, concomitant use of MTX reduced the apparent clearance of golimumab by approximately 36%. However, population pharmacokinetic analysis indicated that concomitant use of NSAIDs, oral corticosteroids or sulfasalazine did not influence the apparent clearance of golimumab.
Following induction doses of 200 mg and 100 mg golimumab at week 0 and week 2, respectively, and maintenance doses of 50 mg or 100 mg Golimumab (Simponi) subcutaneously every 4 weeks thereafter to patients with UC, serum golimumab concentrations reached steady state approximately 14 weeks after the start of therapy. Treatment with 50 mg or 100 mg golimumab subcutaneous every 4 weeks during maintenance resulted in a mean steady‑state trough serum concentration of approximately 0.9 ± 0.5 μg/mL and 1.8 ± 1.1 μg/mL, respectively.
In UC patients treated with 50 mg or 100 mg golimumab subcutaneously every 4 weeks, concomitant use of immunomodulators did not have a substantial effect on steady‑state trough levels of golimumab.
Patients who developed anti‑golimumab antibodies generally had low trough steady‑state serum concentrations of golimumab (see Pharmacology: Pharmacodynamics as previously mentioned).
Linearity: Golimumab exhibited approximately dose‑proportional pharmacokinetics in patients with RA over the dose range of 0.1 to 10.0 mg/kg following a single intravenous dose. Following a single SC dose in healthy subjects, approximately dose‑proportional pharmacokinetics were also observed over a dose range of 50 mg to 400 mg.
Effect of weight on pharmacokinetics: There was a trend toward higher apparent clearance of golimumab with increasing weight (see Dosage & Administration).
Pediatric population: The pharmacokinetics of golimumab were determined in 173 children with pJIA with an age range from 2 to 17 years of age. In the pJIA study, children who received golimumab 30 mg/m² (maximum 50 mg) subcutaneously every 4 weeks, had median steady‑state trough golimumab concentrations which were similar across different age groups, and which were also similar to or slightly higher than those seen in adult RA patients who received 50 mg golimumab every 4 weeks.
Population pharmacokinetic/pharmacodynamic modeling and simulation in children with pJIA confirmed the relationship between golimumab serum exposures and clinical efficacy and supports that the dosing regimen of golimumab 50 mg every 4 weeks in children with pJIA of at least 40 kg achieves similar exposures to those shown to be efficacious in adults.
Toxicology: Pre-clinical safety data: Non‑clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, toxicity to reproduction and development.
No mutagenicity studies, animal fertility studies nor long‑term carcinogenic studies have been conducted with golimumab.
In a fertility and general reproductive function study in mouse, using an analogous antibody that selectively inhibits the functional activity of mouse TNFα, the number of pregnant mice was reduced. It is not known whether this finding was due to effects on the males and/or the females. In a developmental toxicity study conducted in mice following administration of the same analogous antibody, and in cynomolgus monkeys using golimumab, there was no indication of maternal toxicity, embryotoxicity or teratogenicity.

Rheumatoid arthritis (RA): Golimumab (Simponi), by subcutaneous (SC) administration, in combination with methotrexate (MTX), is indicated for: Reducing signs and symptoms; Inducing major clinical response; Inhibiting the progression of structural damage; Improving physical function; Improving health‑related quality of life in adult patients with moderately to severely active rheumatoid arthritis. Golimumab (Simponi) can be used in patients previously treated with TNF inhibitors.
Psoriatic arthritis (PsA): Golimumab (Simponi), by SC administration, alone or in combination with MTX, is indicated for: Reducing signs and symptoms; Improving physical function; Inhibiting the progression of structural damage; Improving enthesitis; Improving psoriasis and psoriatic nail disease; Improving health‑related quality of life in adult patients with active psoriatic arthritis.
Ankylosing spondylitis (AS): Golimumab (Simponi), by SC administration, is indicated for: Reducing signs and symptoms; Improving physical function; Improving health‑related quality of life in adult patients with active ankylosing spondylitis.
Polyarticular juvenile idiopathic arthritis (pJIA): Golimumab (Simponi), by subcutaneous administration, in combination with MTX, is indicated for treatment of polyarticular juvenile idiopathic arthritis in children with a body weight of at least 40 kg, who have responded inadequately to previous therapy with MTX.
Non-radiographic axial spondyloarthritis (nr-Axial SpA): Golimumab (Simponi) by SC administration, is indicated for: Reducing signs and symptoms; Improving spinal mobility; Improving physical function; Improving health-related quality of life in adult patients with severe active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence, who have had an inadequate response to, or are intolerant to, nonsteroidal anti-inflammatory drugs (NSAIDs).
Ulcerative colitis (UC): Golimumab (Simponi), by SC administration, is indicated for: Reducing signs and symptoms; Inducing clinical remission; Inducing mucosal healing; Improving health-related quality of life; Maintaining clinical response; Achieving long-term clinical remission; Achieving long-term mucosal healing in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to conventional therapy.

Golimumab (Simponi) is administered by subcutaneous injection.
Adult patients with: Rheumatoid arthritis/Psoriatic arthritis/Ankylosing spondylitis/Non-radiographic axial spondyloarthritis: 50 mg of Golimumab (Simponi) given as a subcutaneous injection once a month, on the same date each month.
Ulcerative colitis: Patients with body weight less than 80 kg: Golimumab (Simponi) given as an initial dose of 200 mg, followed by 100 mg at Week 2, then 50 mg every 4 weeks, thereafter (see Pharmacology: Pharmacodynamics: Clinical Efficacy under Actions).
Patients with body weight greater than or equal to 80 kg: Golimumab (Simponi) given as an initial dose of 200 mg, followed by 100 mg at Week 2, then 100 mg every 4 weeks, thereafter (see Pharmacology: Pharmacodynamics: Clinical Efficacy under Actions).
During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines.
Available data suggest that clinical response is usually achieved within 12‑14 weeks of treatment (after 4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period.
Golimumab (Simponi) is intended for use under the guidance and supervision of a physician. After proper training in subcutaneous injection technique, a patient may self‑inject with Golimumab (Simponi) if a physician determines that it is appropriate and with medical follow‑up as necessary.
At the time of dosing, if multiple injections are required, the injections should be administered at different sites on the body. Patients should be instructed to inject the full amount of Golimumab (Simponi) according to the directions provided in Instructions for Injecting Golimumab (Simponi) Using a Single‑Use SmartJect Autoinjector/Pre‑Filled Pen under Cautions for Usage.
Special Populations: Pediatrics (17 years of age and younger): The safety and efficacy of Golimumab (Simponi) in pediatric patients aged 17 years and younger for indications other than pJIA have not been established (see Pharmacology: Pharmacodynamics under Actions).
Polyarticular juvenile idiopathic arthritis: 50 mg of Golimumab (Simponi) administered once a month, on the same date each month, for children with a body weight of at least 40 kilograms.
Available data suggest that clinical response is usually achieved within 12 to 14 weeks of treatment (after 3 to 4 doses). Continued therapy should be reconsidered in children who show no evidence of therapeutic benefit within this time period.
Elderly (65 years of age and older): Dose adjustment is not required in elderly patients (see Precautions).
Renal impairment: Specific studies of Golimumab (Simponi) have not been conducted in patients with renal impairment.
Hepatic impairment: Specific studies of Golimumab (Simponi) have not been conducted in patients with hepatic impairment.

Single doses up to 10 mg/kg intravenously have been administered in a clinical study without dose-limiting toxicity. In case of overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse effects and appropriate symptomatic treatment be instituted immediately.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Active tuberculosis (TB) or other severe infections such as sepsis, and opportunistic infections (see Precautions).
Moderate or severe heart failure (NYHA class III/IV) (see Precautions).

Infections: Patients must be monitored closely for infections including tuberculosis before, during and after treatment with Golimumab (Simponi). Because the elimination of golimumab may take up to 5 months, monitoring should be continued throughout this period. Further treatment with Golimumab (Simponi) must not be given if a patient develops a serious infection or sepsis (see Contraindications).
Golimumab (Simponi) should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of Golimumab (Simponi) in patients with a chronic infection or a history of recurrent infection. Patients should be advised of, and avoid exposure to, potential risk factors for infection as appropriate.
Patients taking TNF‑blockers are more susceptible to serious infections.
Bacterial (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections, including fatalities, have been reported in patients receiving Golimumab (Simponi). Some of these serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose them to infections. Patients who develop a new infection while undergoing treatment with Golimumab (Simponi) should be monitored closely and undergo a complete diagnostic evaluation. Administration of Golimumab (Simponi) should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled.
For patients who have resided in or traveled to regions where invasive fungal infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are endemic, the benefits and risks of Golimumab (Simponi) treatment should be carefully considered before initiation or continuation of Golimumab (Simponi) therapy. In at‑risk patients treated with Golimumab (Simponi), an invasive fungal infection should be suspected if they develop a serious systemic illness. Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the care of patients with invasive fungal infections, if feasible.
Tuberculosis: There have been reports of tuberculosis in patients receiving Golimumab (Simponi). It should be noted that in the majority of these reports, tuberculosis was extrapulmonary presenting as either local or disseminated disease.
Before starting treatment with Golimumab (Simponi), all patients must be evaluated for both active and inactive ('latent') tuberculosis. This evaluation should include a detailed medical history with personal history of tuberculosis or possible previous contact with tuberculosis and previous and/or current immunosuppressive therapy. Appropriate screening tests, i.e. tuberculin skin or blood test and chest X-ray, should be performed in all patients (local recommendations may apply). It is recommended that the conduct of these tests should be recorded in the patient's alert card. Prescribers are reminded of the risk of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.
If active tuberculosis is diagnosed, Golimumab (Simponi) therapy must not be initiated (see Contraindications).
If latent tuberculosis is suspected, a physician with expertise in the treatment of tuberculosis should be consulted. In all situations described as follows, the benefit/risk balance of Golimumab (Simponi) therapy should be very carefully considered.
If inactive ('latent') tuberculosis is diagnosed, treatment for latent tuberculosis must be started with anti‑tuberculosis therapy before the initiation of Golimumab (Simponi), and in accordance with local recommendations.
In patients who have several or significant risk factors for tuberculosis and have a negative test for latent tuberculosis, anti‑tuberculosis therapy should be considered before the initiation of Golimumab (Simponi). Use of anti‑tuberculosis therapy should also be considered before the initiation of Golimumab (Simponi) in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed.
Cases of active tuberculosis have occurred in patients treated with Golimumab (Simponi) during and after treatment for latent tuberculosis. Patients receiving Golimumab (Simponi) should be monitored closely for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis, patients who are on treatment for latent tuberculosis, or patients who were previously treated for tuberculosis infection.
All patients should be informed to seek medical advice if signs/symptoms suggestive of tuberculosis (e.g. persistent cough, wasting/weight loss, low‑grade fever) appear during or after Golimumab (Simponi) treatment.
Hepatitis B virus reactivation: Reactivation of hepatitis B has occurred in patients receiving a TNF‑antagonist including Golimumab (Simponi), who are chronic carriers of this virus (i.e. surface antigen positive). Some cases have had fatal outcome.
Patients should be tested for HBV infection before initiating treatment with immunosuppressants, including Golimumab (Simponi). For patients who test positive for hepatitis B surface antigen, consultation with a physician with expertise in the treatment of hepatitis B is recommended.
Carriers of HBV who require treatment with Golimumab (Simponi) should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. Adequate data of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF-antagonist therapy to prevent HBV reactivation are not available. In patients who develop HBV reactivation, Golimumab (Simponi) should be stopped and effective anti‑viral therapy with appropriate supportive treatment should be initiated.
Malignancies and lymphoproliferative disorders: The potential role of TNF‑blocking therapy in the development of malignancies is not known. Based on the current knowledge, a possible risk for the development of lymphomas, leukemia or other malignancies in patients treated with a TNF‑antagonist cannot be excluded. Caution should be exercised when considering TNF‑blocking therapy for patients with a history of malignancy or when considering continuing treatment in patients who develop malignancy.
Pediatric malignancy: Malignancies, some fatal, have been reported among children, adolescents, and young adults (up to 22 years of age) who received TNF‑blocking agents (initiation of therapy ≤ 18 years of age) in the post marketing setting. Approximately half of the cases were lymphomas. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression. A risk for the development of malignancies in children and adolescents treated with TNF‑blockers cannot be excluded.
Lymphoma and leukemia: In the controlled portions of clinical trials of all the TNF‑blocking agents including Golimumab (Simponi), more cases of lymphoma have been observed among patients receiving anti‑TNF treatment compared with control patients. During the Golimumab (Simponi) Phase IIb and Phase III clinical trials in RA, PsA and AS, the incidence of lymphoma in Golimumab (Simponi)‑treated patients was higher than expected in the general population. Cases of leukemia have been reported in patients treated with Golimumab (Simponi). There is an increased background risk for lymphoma and leukemia in rheumatoid arthritis patients with long‑standing, highly active, inflammatory disease, which complicates risk estimation.
Rare post-marketing cases of hepatosplenic T‑cell lymphoma (HSTCL) have been reported in patients treated with other TNF‑blocking agents (see Adverse Reactions). This rare type of T‑cell lymphoma has a very aggressive disease course and is usually fatal. The majority of cases have occurred in adolescent and young adult males with nearly all on concomitant treatment with azathioprine (AZA) or 6‑mercaptopurine (6-MP) for inflammatory bowel disease. The potential risk with the combination of AZA or 6‑MP and Golimumab (Simponi) should be carefully considered. A risk for the development for hepatosplenic T‑cell lymphoma in patients treated with TNF-blockers cannot be excluded.
Malignancies other than lymphoma: In the controlled portions of the Golimumab (Simponi) Phase IIb and Phase III clinical trials in RA, PsA, AS and UC, the incidence of non‑lymphoma malignancies (excluding non-melanoma skin cancer) was similar between the Golimumab (Simponi) and the control groups.
Colon dysplasia/carcinoma: It is not known if golimumab treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations. In patients with newly diagnosed dysplasia treated with Golimumab (Simponi), the risks and benefits to the individual patient must be carefully reviewed and consideration should be given to whether therapy should be continued.
In an exploratory clinical trial evaluating the use of Golimumab (Simponi) in patients with severe persistent asthma, more malignancies were reported in patients treated with Golimumab (Simponi) compared with control patients (see Adverse Reactions). The significance of this finding is unknown.
In an exploratory clinical trial evaluating the use of another anti‑TNF agent, infliximab, in patients with moderate to severe chronic obstructive pulmonary disease (COPD), more malignancies, mostly in the lung or head and neck, were reported in infliximab‑treated patients compared with control patients. All patients had a history of heavy smoking.
Therefore, caution should be exercised when using any TNF‑antagonist in COPD patients, as well as in patients with an increased risk of malignancy due to heavy smoking.
Skin cancers: Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF‑blocking agents, including Golimumab (Simponi) (see Adverse Reactions). Periodic skin examination is recommended for all patients, particularly for patients with risk factors for skin cancer.
Congestive heart failure (CHF): Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers, including Golimumab (Simponi). Some cases had a fatal outcome. In a clinical trial with another TNF‑antagonist worsening congestive heart failure and increased mortality due to CHF have been observed. Golimumab (Simponi) has not been studied in patients with CHF. Golimumab (Simponi) should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored, and Golimumab (Simponi) must be discontinued who develop new or worsening symptoms of heart failure (see Contraindications).
Neurological events: Use of TNF‑blocking agents, including Golimumab (Simponi), has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and peripheral demyelinating disorders. In patients with pre‑existing or recent onset of demyelinating disorders, the benefits and risks of anti‑TNF treatment should be carefully considered before initiation of Golimumab (Simponi) therapy. Discontinuation of Golimumab (Simponi) should be considered if these disorders develop (see Adverse Reactions).
Surgery: There is limited safety experience of Golimumab (Simponi) treatment in patients who have undergone surgical procedures, including arthroplasty. The long half‑life should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on Golimumab (Simponi) should be closely monitored for infections, and appropriate actions should be taken.
Immunosuppression: The possibility exists for TNF‑blocking agents, including Golimumab (Simponi), to affect host defences against infections and malignancies since TNF mediates inflammation and modulates cellular immune responses.
Autoimmune processes: The relative deficiency of TNF_α caused by anti‑TNF therapy may result in the initiation of an autoimmune process. If a patient develops symptoms suggestive of a lupus‑like syndrome following treatment with Golimumab (Simponi) and is positive for antibodies against double-stranded DNA, treatment with Golimumab (Simponi) should be discontinued (see Adverse Reactions).
Hematologic reactions: There have been reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, and thrombocytopenia in patients receiving TNF blockers, including Golimumab (Simponi). All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g. persistent fever, bruising, bleeding, pallor). Discontinuation of Golimumab (Simponi) therapy should be considered in patients with confirmed significant hematologic abnormalities.
Concurrent administration of TNF-antagonists with anakinra: Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and another TNF‑blocking agent, etanercept, with no added clinical benefit. Because of the nature of the adverse events seen with this combination therapy, similar toxicities may also result from the combination of anakinra and other TNF‑blocking agents. The combination of Golimumab (Simponi) and anakinra is not recommended.
Concurrent administration of TNF-antagonists and abatacept: In clinical studies concurrent administration of TNF‑antagonists and abatacept has been associated with an increased risk of infections including serious infections compared with TNF‑blocking agents alone, without increased clinical benefit. The combination of Golimumab (Simponi) and abatacept is not recommended.
Concurrent administration with other biological therapeutics: There is insufficient information regarding the concomitant use of Golimumab (Simponi) with other biological therapeutics used to treat the same conditions as Golimumab (Simponi). The concomitant use of Golimumab (Simponi) with these biologics is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions.
Concurrent administration with other biological therapeutics: There is insufficient information regarding the concomitant use of Golimumab (Simponi) with other biological therapeutics used to treat the same conditions as Golimumab (Simponi). The concomitant use of Golimumab (Simponi) with these biologics is not recommended because of the possibility of an increased risk of infection, and other potential pharmacological interactions.
Switching between biological DMARDs: Care should be taken and patients should continue to be monitored when switching from one biologic to another, since overlapping biological activity may further increase the risk for adverse events, including infection.
Vaccinations/therapeutic infectious agents: Patients treated with Golimumab (Simponi) may receive concurrent vaccinations, except for live vaccines (see Interactions and Use in Pregnancy & Lactation). In patients receiving anti‑TNF therapy, limited data are available on the response to vaccination with live vaccines or on the secondary transmission of infection by live vaccines. Use of live vaccines could result in clinical infections, including disseminated infections.
Other uses of therapeutic infectious agents such as live attenuated bacteria (e.g., BCG bladder instillation for the treatment of cancer) could result in clinical infections, including disseminated infections. It is recommended that therapeutic infectious agents not be given concurrently with Golimumab (Simponi).
Allergic reactions: In post‑marketing experience, serious systemic hypersensitivity reactions (including anaphylactic reaction) have been reported following Golimumab (Simponi) administration.
Some of these reactions occurred after the first administration of Golimumab (Simponi). If an anaphylactic reaction or other serious allergic reactions occur, administration of Golimumab (Simponi) should be discontinued immediately and appropriate therapy initiated.
Latex sensitivity: The needle cover on the pre‑filled syringe contains dry natural rubber containing latex, and may cause allergic reactions in individuals sensitive to latex.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Golimumab (Simponi) may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Golimumab (Simponi) (see Adverse Reactions).
Special populations: Renal and hepatic impairment: Specific studies of Golimumab (Simponi) have not been conducted in patients with renal or hepatic impairment. Golimumab (Simponi) should be used with caution in subjects with impaired hepatic function (see Dosage & Administration).
Use in Children: Vaccinations: If possible, it is recommended that prior to initiating Golimumab (Simponi) therapy, pediatric patients be brought up to date with all immunization in agreement with current immunization guidelines.
Excipients: Golimumab (Simponi) contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take Golimumab (Simponi).
Use in the Elderly (≥ 65 years): In the Phase III studies in RA, PsA, AS and UC, no overall differences in adverse events (AEs), serious adverse events (SAEs), and serious infections in patients age 65 or older who received Golimumab (Simponi) were observed compared with younger patients. However, caution should be used in treating the elderly and particular attention paid with respect to occurrence of infections. There were no patients age 45 and over in the nr‑Axial SpA study.

Women of childbearing potential: Women of childbearing potential must use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last golimumab treatment.
Pregnancy: There are no adequate data on the use of golimumab in pregnant women. Due to its inhibition of TNF, golimumab administered during pregnancy could affect normal immune responses in the newborn. Studies in animals do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). The use of golimumab in pregnant women is not recommended; golimumab should be given to a pregnant woman only if clearly needed.
Golimumab crosses the placenta. Following treatment with a TNF‑blocking monoclonal antibody during pregnancy, the antibody has been detected for up to 6 months in the serum of the infant born by the treated woman. Consequently, these infants may be at increased risk of infection. Administration of live vaccines to infants exposed to golimumab in utero is not recommended for 6 months following the mother's last golimumab injection during pregnancy (see Precautions and Interactions).
Breast‑feeding: It is not known whether golimumab is excreted in human milk or absorbed systemically after ingestion. Golimumab was shown to pass over to breast milk in monkeys, and because human immunoglobulins are excreted in milk, women must not breast feed during and for at least 6 months after golimumab treatment.
Fertility: No animal fertility studies have been conducted with golimumab. A fertility study in mice, using an analogous antibody that selectively inhibits the functional activity of mouse TNFα, showed no relevant effects on fertility (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).

Summary of the safety profile: In the controlled period of the pivotal trials in RA, PsA, AS, nr‑Axial SpA, and UC, upper respiratory tract infection was the most common adverse drug reaction (ADR) reported in 12.6% of golimumab‑treated patients compared with 11.0% of control patients. The most serious ADRs that have been reported for golimumab include serious infections (including sepsis, pneumonia, TB, invasive fungal and opportunistic infections), demyelinating disorders, HBV reactivation, CHF, autoimmune processes (lupus‑like syndrome), hematologic reactions, serious systemic hypersensitivity (including anaphylactic reaction), vasculitis, lymphoma and leukemia (see Precautions).
Tabulated list of adverse reactions: ADRs observed in clinical studies and reported from world‑wide post‑marketing use of golimumab are listed in Table 8. Within the designated system organ classes, the adverse drug reactions are listed under headings of frequency and using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. (See Table 8.)

Click on icon to see table/diagram/image

Throughout this section, median duration of follow-up (approximately 4 years) is generally presented for all golimumab use. Where golimumab use is described by dose, the median duration of follow-up varies (approximately 2 years for 50 mg dose, approximately 3 years for 100 mg dose) as patients may have switched between doses.
Description of selected adverse drug reactions: Infections: In the controlled period of pivotal trials, upper respiratory tract infection was the most common adverse reaction reported in 12.6% of golimumab‑treated patients (incidence per 100 subject‑years: 60.8; 95% CI: 55.0, 67.1) compared with 11.0% of control patients (incidence per 100 subject‑years: 54.5; 95% CI: 46.1, 64.0). In controlled and uncontrolled portions of the studies with a median follow‑up of approximately 4 years, the incidence per 100 subject‑years of upper respiratory tract infections was 34.9 events; 95% CI: 33.8, 36.0 for golimumab treated patients.
In the controlled period of pivotal trials, infections were observed in 23.0% of golimumab‑treated patients (incidence per 100 subject‑years: 132.0; 95% CI: 123.3, 141.1) compared with 20.2% of control patients (incidence per 100 subject‑years: 122.3; 95% CI: 109.5, 136.2). In controlled and uncontrolled portions of the trials with a median follow‑up of approximately 4 years, the incidence per 100 subject‑years of infections was 81.1 events; 95% CI: 79.5, 82.8 for golimumab treated patients.
In the controlled period of RA, PsA, AS, and nr‑Axial SpA trials, serious infections were observed in 1.2% of golimumab‑treated patients and 1.2% of control‑treated patients. The incidence of serious infections per 100 subject‑years of follow‑up in the controlled period of RA, PsA, AS, and nr‑Axial SpA trials was 7.3; 95% CI: 4.6, 11.1 for the golimumab 100 mg group, 2.9; 95% CI: 1.2, 6.0 for the golimumab 50 mg group and 3.6; 95% CI: 1.5, 7.0 for the placebo group. In the controlled period of UC trials of golimumab induction, serious infections were observed in 0.8% of golimumab-treated patients compared with 1.5% of control-treated patients. Serious infections observed in golimumab‑treated patients included tuberculosis, bacterial infections including sepsis and pneumonia, invasive fungal infections and other opportunistic infections. Some of these infections have been fatal. In the controlled and uncontrolled portions of the pivotal trials with a median follow‑up of up to 3 years, there was a greater incidence of serious infections, including opportunistic infections and TB in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. The incidence per 100 subject‑years of all serious infections was 4.1; 95% CI: 3.6, 4.5, in patients receiving golimumab 100 mg and 2.5; 95% CI: 2.0, 3.1, in patients receiving golimumab 50 mg.
Malignancies: Lymphoma: The incidence of lymphoma in golimumab-treated patients during the pivotal trials was higher than expected in the general population. In the controlled and uncontrolled portions of these trials with a median follow‑up of up to 3 years, a greater incidence of lymphoma was observed in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. Lymphoma was diagnosed in 11 subjects (1 in the golimumab 50 mg treatment groups and 10 in the golimumab 100 mg treatment groups) with an incidence (95% CI) per 100 subject‑years of follow-up of 0.03 (0.00, 0.15) and 0.13 (0.06, 0.24) events for golimumab 50 mg and 100 mg respectively and 0.00 (0.00, 0.57) events for the placebo.
The majority of lymphomas occurred in study GO‑AFTER, which enrolled patients previously exposed to anti‑TNF agents who had longer disease duration and more refractory disease (see Precautions).
Malignancies other than lymphoma: In the controlled periods of pivotal trials and through approximately 4 years of follow‑up, the incidence of non‑lymphoma malignancies (excluding non‑melanoma skin cancer) was similar between the golimumab and the control groups. Through approximately 4 years of follow-up, the incidence of non-lymphoma malignancies (excluding non-melanoma skin cancer) was similar to the general population.
In the controlled and uncontrolled periods of pivotal trials with a median follow-up of up to 3 years, non-melanoma skin cancer was diagnosed in 5 placebo-treated, 10 golimumab 50 mg-treated and 31 golimumab 100 mg-treated subjects with an incidence (95% CI) per 100 subject‑years of follow-up of 0.36 (0.26, 0.49) for combined golimumab and 0.87 (0.28, 2.04) for placebo.
In the controlled and uncontrolled period of pivotal trials with a median follow-up of up to 3 years, malignancies besides melanoma, non-melanoma skin cancer and lymphoma were diagnosed in 5 placebo-treated, 21 golimumab 50 mg-treated and 34 golimumab 100 mg-treated subjects with an incidence (95% CI) per 100 subject‑years of follow‑up of 0.48 (0.36, 0.62) for combined golimumab and 0.87 (0.28, 2.04) for placebo (see Precautions).
Cases reported in clinical studies in asthma: In an exploratory clinical study, patients with severe persistent asthma received a golimumab loading dose (150% of the assigned treatment dose) subcutaneously at week 0 followed by golimumab 200 mg, golimumab 100 mg or golimumab 50 mg every 4 weeks subcutaneously through week 52. Eight malignancies in the combined golimumab treatment group (n = 230) and none in the placebo treatment group (n = 79) were reported. Lymphoma was reported in 1 patient, non‑melanoma skin cancer in 2 patients, and other malignancies in 5 patients. There was no specific clustering of any type of malignancy.
During the placebo‑controlled portion of the study, the incidence (95% CI) of all malignancies per 100 subject‑years of follow‑up was 3.19 (1.38, 6.28) in the golimumab group. In this study, the incidence (95% CI) per 100 subject‑years of follow‑up in golimumab‑treated subjects was 0.40 (0.01, 2.20) for lymphoma, 0.79 (0.10, 2.86) for non‑melanoma skin cancers, and 1.99 (0.64, 4.63) for other malignancies. For placebo subjects, the incidence (95% CI) per 100 subject‑years of follow‑up of these malignancies was 0.00 (0.00, 2.94). The significance of this finding is unknown.
Neurological events: In the controlled and uncontrolled periods of the pivotal trials with a median follow‑up of up to 3 years, a greater incidence of demyelination was observed in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg (see Precautions).
Liver enzyme elevations: In the controlled period of RA and PsA pivotal trials, mild ALT elevations (> 1 and < 3 x upper limit of normal (ULN)) occurred in similar proportions of golimumab and control patients in the RA and PsA studies (22.1% to 27.4% of patients); in the AS and nr‑Axial SpA studies, more golimumab‑treated patients (26.9%) than control patients (10.6%) had mild ALT elevations. In the controlled and uncontrolled periods of the RA and PsA pivotal trials, with a median follow-up of approximately 5 years, the incidence of mild ALT elevations was similar in golimumab‑treated and control patients in RA and PsA studies. In the controlled period of the UC pivotal trials of golimumab induction, mild ALT elevations (> 1 and < 3 x ULN) occurred in similar proportions of golimumab‑treated and control patients (8.0% to 6.9%, respectively). In controlled and uncontrolled periods of the UC pivotal trials with a median follow-up of approximately 2 years, the proportion of patients with mild ALT elevations was 24.7% in patients receiving golimumab during the maintenance portion of the UC study.
In the controlled period of RA and AS pivotal trials, ALT elevations ≥ 5 x ULN were uncommon and seen in more golimumab‑treated patients (0.4% to 0.9%) than control patients (0.0%). This trend was not observed in the PsA population. In the controlled and uncontrolled periods of RA, PsA and AS pivotal trials, with a median follow-up of 5 years, the incidence of ALT elevations ≥ 5 x ULN was similar in both golimumab‑treated and control patients. In general these elevations were asymptomatic and the abnormalities decreased or resolved with either continuation or discontinuation of golimumab or modification of concomitant medicinal products. No cases were reported in the controlled and uncontrolled periods of the nr‑Axial SpA study (up to 1 year). In the controlled periods of the pivotal UC trials, of golimumab induction, ALT elevations ≥ 5 x ULN occurred in similar proportions of golimumab‑treated patients compared to placebo-treated patients (0.3% to 1.0%, respectively). In the controlled and uncontrolled periods of the pivotal UC trials with a median follow-up of approximately 2 years, the proportion of patients with ALT elevations ≥ 5 x ULN was 0.8% in patients receiving golimumab during the maintenance portion of the UC study.
Within the RA, PsA, AS, and nr‑Axial SpA pivotal trials, one patient in an RA trial with pre‑existing liver abnormalities and confounding medicinal products treated with golimumab developed non‑infectious fatal hepatitis with jaundice. The role of golimumab as a contributing or aggravation factor cannot be excluded.
Injection site reactions: In the controlled periods of pivotal trials, 5.4% of golimumab‑treated patients had injection site reactions compared with 2.0% in control patients. The presence of antibodies to golimumab may increase the risk of injection site reactions. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema. Injection site reactions generally did not necessitate discontinuation of the medicinal product.
In controlled Phase IIb and/or III trials in RA, PsA, AS, nr‑Axial SpA, severe persistent asthma, and Phase II/III trials in UC, no patients treated with golimumab developed anaphylactic reactions.
Autoimmune antibodies: In the controlled and uncontrolled periods of pivotal trials through 1 year of follow-up, 3.5% of golimumab‑treated patients and 2.3% of control patients were newly ANA‑positive (at titres of 1:160 or greater). The frequency of anti‑dsDNA antibodies at 1 year of follow-up in patients anti‑dsDNA negative at baseline was 1.1%.
Pediatric population: Polyarticular juvenile idiopathic arthritis: The safety of golimumab has been studied in a phase III study of 173 pJIA patients from 2 to 17 years of age. The average follow-up was approximately two years. In this study, the type and frequency of adverse events reported were generally similar to those seen in adult RA studies.

No interaction studies have been performed.
Concurrent use of Golimumab (Simponi) with other biological therapeutics: The combination of Golimumab (Simponi) with other biological therapeutics used to treat the same conditions as Golimumab (Simponi), including anakinra and abatacept, is not recommended (see Precautions).
Live vaccines/therapeutic infectious agents: Live vaccines should not be given concurrently with Golimumab (Simponi) (Precautions and Use in Pregnancy & Lactation).
Therapeutic infectious agents should not be given concurrently with Golimumab (Simponi) (see Precautions).
Methotrexate: Although concomitant use of MTX results in higher steady‑state trough concentrations of Golimumab (Simponi) in patients with RA, PsA, or AS, the data do not suggest the need for dose adjustment of either Golimumab (Simponi) or MTX (see Pharmacology: Pharmacokinetics under Actions).

INCOMPATIBILITIES: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING: Golimumab (Simponi) is supplied in a single use pre‑filled pen/autoinjector (SmartJect) called SmartJect.
Each Golimumab (Simponi) pack is provided with instructions for use that fully describe the use of the pen/autoinjector (SmartJect). After removing the pre‑filled pen/autoinjector (SmartJect) from the refrigerator it should be allowed to reach room temperature by waiting for 30 minutes, before injecting Golimumab (Simponi). The pen/autoinjector (SmartJect) should not be shaken.
The solution is clear to slightly opalescent, colorless to light yellow and may contain a few small translucent or white particles of protein. This appearance is not unusual for solutions containing protein. Golimumab (Simponi) should not be used if the solution is discolored, cloudy or containing visible foreign particles.
Comprehensive instructions for the preparation and administration of Golimumab (Simponi) in a pre‑filled pen/autoinjector (SmartJect) are given as follows.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
INSTRUCTIONS FOR INJECTING GOLIMUMAB (SIMPONI) USING A SINGLE-USE AUTOINJECTOR/PRE-FILLED PEN/AUTOINJECTOR (SMARTJECT): If the patient would like to self‑inject Golimumab (Simponi), he/she must be trained by a healthcare professional to prepare an injection and give it to themselves. If the patient have not been trained, please contact a healthcare professional to schedule a training session.
STEP 1: PREPARING TO USE THE AUTOINJECTOR: DO NOT shake the autoinjector at any time.
DO NOT remove the autoinjector cap from the pen/autoinjector (SmartJect) until immediately before the injection.
Check Expiration Date: Check the expiration date (indicated as "EXP") on the autoinjector.
The patient can also check the expiration date printed on the carton.
If the expiration date has passed, DO NOT use the autoinjector and please contact a doctor, pharmacist, or local distributor of this medicine for assistance.
Check Security Seal: Check the security seal around the cap of the autoinjector. If the security seal is broken, DO NOT use the autoinjector and please contact a doctor, pharmacist, or local distributor of this medicine for assistance.
Wait 30 Minutes: To ensure proper injection, allow the autoinjector to sit at room temperature outside the carton for 30 minutes out of the reach of children.
DO NOT warm the autoinjector in any other way (for example, DO NOT warm it in a microwave or in hot water).
DO NOT remove the autoinjector cap while allowing it to reach room temperature.
Assemble Additional Supplies: Assemble additional supplies that will be needed for the injection. These include an alcohol swab, a cotton ball or gauze, and a sharps container.
Check the Liquid in the Autoinjector: Look through the viewing window to make sure that the liquid in the autoinjector is clear to slightly opalescent and colorless to slightly yellow.
The patient may also notice an air bubble - this is normal.
DO NOT use if the liquid is discolored, cloudy or contains particles. If this is the case, please contact a doctor, pharmacist, or local distributor of this medicine for assistance.
STEP 2: CHOOSING AND PREPARING THE INJECTION SITE: Choose the Injection Site: The recommended injection site is the front of the middle thighs.
The patient can also use the lower abdomen below the belly button, except for the two‑inch area directly underneath the belly button.
If a caregiver is giving the injection, the caregiver can also use the outer area of the upper arms.
If multiple injections are required for a single administration, the injections should be administered at different sites on the body.
DO NOT inject into areas where the skin is tender, bruised, red, scaly, or hard. Avoid areas with scars or stretch marks.
Preparing Injection Site: Thoroughly wash hands with soap and warm water.
Wipe the injection site with an alcohol swab.
DO NOT touch this area again before giving the injection. Allow the skin to dry before injecting.
DO NOT fan or blow on the clean area.
STEP 3: INJECTING THE MEDICINE: Remove the Cap: The cap should NOT be removed until the patient are ready to inject the medication. The medication should be injected within 5 minutes after the cap has been removed.
When ready to inject, twist the cap slightly to break the security seal.
Pull the cap off and immediately place the cap into the trash.
DO NOT put the cap back on because it may damage the needle inside the autoinjector.
Note: DO NOT use autoinjector if it is dropped without the cap in place. If the patient drops the autoinjector without the cap in place, contact a doctor, pharmacist, or local distributor of this medicine for assistance.
Push the Autoinjector Against the Skin: Hold the autoinjector comfortably in the hand. DO NOT press the button at this time.
Push the open end of the autoinjector firmly against the skin at a 90‑degree angle.
DO NOT press the button until after the autoinjector is pushed firmly against the skin and the Safety Sleeve slides fully into the Clear Cover.
Injecting without pinching the skin is recommended. However, if the patient prefers, he/she may pinch the skin to create a firmer surface for the injection.
Press Button to Inject: Continue to hold the autoinjector firmly against the skin, and press the front raised part of the button with the fingers or thumb. The patient will not be able to press in the button unless the autoinjector is pushed firmly against the skin and the Safety Sleeve slides into the Clear Cover.
Once the button is pressed, it will remain pressed in so the patient do not need to keep pressure on it.
The patient will hear a loud 'click' sound - don't be alarmed. The first loud 'click' indicates that the needle has been inserted and the injection has started. The patient may or may not feel a needle prick at this time.
DO NOT lift the autoinjector away from the skin. If the patient pull the autoinjector away from the skin, he/she may not get the full dose of medicine.
Wait for Second 'Click': Continue to hold the autoinjector against the skin until the patient hears the second 'click' (it usually takes about 3 to 6 seconds, but may take up to 15 seconds for the patient to hear the second 'click' sound).
The second 'click' indicates that the injection is finished and the needle has retracted into the autoinjector. Note: If the patient has a hearing problem and do not hear the second 'click', count 15 seconds from the time the patient first presses the button and then lift the autoinjector from the injection site.
Lift the autoinjector from the injection site.
STEP 4: AFTER THE INJECTION: Check the Viewing Window: After injecting, check the viewing window to make sure that the yellow indicator is visible.
The yellow indicator may not fill the entire viewing window. This is normal.
This indicates that the autoinjector has worked properly.
If the patient does not think he/she received the injection, check the yellow indicator again to confirm that the dose was delivered.
If the yellow indicator is not visible in the viewing window, call a doctor, pharmacist, or local distributor of this medicine for assistance. DO NOT administer a second dose without speaking to a doctor.
Disposing of the Autoinjector: Immediately dispose of the autoinjector in the sharps container.
Dispose of the sharps container according to the local regulations when the container is full.
Use Cotton Ball or Gauze: There may be a small amount of blood or liquid at the injection site, which is normal.
The patient can press a cotton ball or gauze over the injection site for 10 seconds. DO NOT rub the injection site.
The patient may cover the injection site with a small adhesive bandage, if necessary.

Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep the pre‑filled pen/autoinjector (SmartJect) in the outer carton in order to protect it from light.
Golimumab (Simponi) pre-filled pen may be stored at room temperature up to a maximum of 25°C for a single period of up to 30 days in the original carton; after which it should not be refrigerated again. Golimumab (Simponi) must be protected from light. It should be discarded if not used within 30 days of removal from refrigeration.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs) / Immunosuppressants

L04AB06 - golimumab ; Belongs to the class of tumor necrosis factor alpha (TNF-alpha) inhibitors. Used as immunosuppressants.

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