Stelara Adverse Reactions

Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of ustekinumab based on the comprehensive assessment of the available adverse event information. A causal relationship with ustekinumab cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical Studies Experience in Adult Patients with Psoriasis, Psoriatic Arthritis, Crohn's Disease, and Ulcerative Colitis: The safety data described as follows reflect exposure to Ustekinumab (Stelara) in 14 Phase 2 and Phase 3 studies in 6709 patients (4135 with psoriasis and/or psoriatic arthritis, 1749 for Crohn's disease, and 825 with ulcerative colitis in UC-1 and UC-2 clinical trials), with duration of exposure to Ustekinumab (Stelara) presented in Table 30. (See Table 30.)

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The most common adverse reactions (>5%) in controlled periods of the clinical studies with Ustekinumab (Stelara) among all indications were nasopharyngitis and headache. Most were considered to be mild and did not necessitate drug discontinuation. The overall safety profile of Ustekinumab (Stelara) was similar for patients among all indications.
Table 31 provides a summary of Adverse Reactions from the clinical studies. The frequency of these adverse reactions was based on those that occurred during the initial controlled periods of the clinical studies. The adverse reactions are ranked by frequency, using the following convention: Very common (≥1/10); Common (frequent) (≥1/100, <1/10); Uncommon (infrequent) (≥1/1000, <1/100); Rare (≥1/10000, <1/1000). (See Table 31.)

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Infections: In the placebo-controlled studies of patients with psoriasis, psoriatic arthritis, Crohn's Disease and ulcerative colitis, the rates of infection or serious infection were similar between Ustekinumab (Stelara)-treated patients and those treated with placebo. In the placebo-controlled period of clinical studies of patients with psoriasis, patients with psoriatic arthritis, patients with Crohn's disease, and patients with ulcerative colitis, the rate of infection was 1.36 per patient-year of follow-up in Ustekinumab (Stelara)-treated patients, and 1.34 per patient-year of follow-up in placebo-treated patients. Serious infections occurred at a rate of 0.03 per patient-year of follow-up in Ustekinumab (Stelara)-treated patients (30 serious infections in 930 patient-years of follow-up) and 0.03 per patient-year of follow-up in placebo-treated patients (15 serious infections in 434 patient-years of follow-up) (see Precautions).
In the controlled and non-controlled periods of psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis, clinical studies representing 11581 patient-years of exposure in 6709 patients, the median follow-up was 1.0 years; 1.1 years for psoriatic disease studies, and 0.6 year for Crohn's disease studies, and 1.0 years for ulcerative colitis studies. The rate of infection was 0.91 per patient-year of follow-up in Ustekinumab (Stelara)-treated patients. The rate of serious infections was 0.02 per patient-year of follow-up in Ustekinumab (Stelara)-treated patients (199 serious infections in 11581 patient-years of follow-up) and included pneumonia, anal abscess, cellulitis, diverticulitis, gastroenteritis and viral infections.
In clinical studies, patients with latent tuberculosis who were concurrently treated with isoniazid did not develop tuberculosis.
Malignancy: In the placebo-controlled period of the psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis clinical studies, the incidence of malignancies excluding nonmelanoma skin cancer was 0.11 per 100 patient-years of follow-up for Ustekinumab (Stelara)-treated patients (1 patient in 929 patient-years of follow-up) compared with 0.23 per 100 patient-years of follow-up for placebo-treated patients (1 patient in 434 patient-years of follow-up). The incidence of non-melanoma skin cancer was 0.43 per 100 patient-years of follow-up for Ustekinumab (Stelara)-treated patients (4 patients in 929 patient-years of follow-up) compared with 0.46 per 100 patient years of follow-up for placebo-treated patients (2 patients in 433 patient-years of follow-up).
In the controlled and non-controlled periods of psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis clinical studies representing 11561 patient-years of exposure in 6709 patients, the median follow-up was 1.0 years; 1.1 years for psoriatic disease studies, 0.6 year for Crohn's disease studies, and 1.0 years for ulcerative colitis studies. Malignancies, excluding non-melanoma skin cancers, were reported in 62 patients in 11561 patient-years of follow-up (incidence of 0.54 per 100 patient years of follow-up for Ustekinumab (Stelara)-treated patients). The incidence of malignancies, reported in Ustekinumab (Stelara)-treated patients was comparable to the incidence expected in the general population (standardized incidence ratio = 0.93 [95% confidence interval: 0.71, 1.20], adjusted for age, gender and race)¹. The most frequently observed malignancies, other than non-melanoma skin cancer, were prostate, colorectal, melanoma, and breast. The incidence of non-melanoma skin cancer was 0.49 per 100 patient-years of follow-up for Ustekinumab (Stelara)-treated patients (56 patients in 11545 patient-years of follow-up). The ratio of patients with basal versus squamous cell skin cancers (3:1) is comparable with the ratio expected in the general population (see Precautions).
¹Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER 6.6.2 Regs Research Data, Nov 2009 Sub (1973-2007) - Linked To County Attributes - Total U.S., 1969-2007 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, Surveillance Systems Branch, released April 2010, based on the November 2009 submission.
Hypersensitivity and Infusion Reactions: Subcutaneous administration: During the controlled periods of the psoriasis and psoriatic arthritis clinical studies of Ustekinumab (Stelara), rash and urticaria have each been observed in <1% of patients.
IV administration: In Crohn's disease and ulcerative colitis intravenous induction studies, no events of anaphylaxis or other serious infusion reactions were reported. In Crohn's disease studies, 2.4% of 466 placebo treated patients and 2.6% of 470 patients treated with the recommended dose of Ustekinumab (Stelara) reported adverse events occurring during or within an hour of the infusion. In ulcerative colitis studies, 1.9% of 319 placebo patients and 0.9% of 320 patients treated with the recommended dose of Ustekinumab (Stelara) reported adverse events occurring during or within an hour of the infusion.
Immunogenicity: In psoriasis and psoriatic arthritis clinical studies, up to 12.4% of patients treated with Ustekinumab (Stelara) developed antibodies to ustekinumab. Patients positive for antibodies to ustekinumab tended to have lower efficacy, however, antibody positivity did not preclude a clinical response. The majority of patients who were positive for antibodies to ustekinumab had neutralizing antibodies. In Crohn's disease and ulcerative colitis clinical studies, 2.9% and 4.6% of patients, respectively, developed antibodies to ustekinumab when treated with ustekinumab for approximately one year. No apparent association between the development of antibodies to ustekinumab and the development of injection site reactions was observed.
Post Marketing Experience: The adverse reactions in Table 32 are ranked by frequency* using the following convention: Very common: ≥1/10; Common: ≥1/100 and <1/10; Uncommon: ≥1/1000 and <1/100; Rare: ≥1/10000 and <1/1000; Very rare: <1/10000, including isolated reports. (See Table 32.)

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