Taltz Adverse Reactions

Summary of the safety profile: The most frequently reported adverse drug reactions (ADRs) were injection site reactions (15.5%) and upper respiratory tract infections (16.4%) (most frequently nasopharyngitis).
Tabulated list of adverse reactions: ADRs from clinical studies and postmarketing reports (Table 13) are listed by MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each ADR is based on 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).
A total of 8,956 patients have been treated with Taltz in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, axial spondyloarthritis and other autoimmune conditions. Of these, 6,385 patients were exposed to Taltz for at least one year, cumulatively representing 19,833 adult patient years of exposure and 196 children cumulatively representing 207 patient years of exposure.
In plaque psoriasis in adults a total of 3,119 patients were evaluated in clinical trials (2,328 patients on ixekizumab).
In psoriatic arthritis in adults a total of 678 patients were evaluated in clinical trials (454 patients on ixekizumab).
In axial spondyloarthritis (radiographic and non-radiographic axSpA) a total of 868 patients were evaluated in clinical trials (574 patients on ixekizumab). (See Table 13.)

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Description of selected adverse reactions: (Based on adverse reactions data from 4,204 patients with moderate to severe plaque psoriasis [4,729.7 patient years] and 1,117 patients with active psoriatic arthritis [1,050.6 patient years] and 196 patients with paediatric psoriasis [207 patient years] who have received at least 1 dose of ixekizumab.)
Injection site reactions: The most frequent injection site reactions observed were erythema and pain. These reactions were predominantly mild to moderate in severity and did not lead to discontinuation of Taltz.
In the adult plaque psoriasis studies, injection site reactions were more common in subjects with a body weight < 60 kg compared with the group with a body weight ≥ 60 kg (25% vs. 14% for the combined Q2W and Q4W groups). In the psoriatic arthritis studies, injection site reactions were more common in subjects with a body weight < 100 kg compared with the group with a body weight ≥ 100 kg (24% vs. 13% for the combined Q2W and Q4W groups). In the axial spondyloarthritis studies, injection site reactions were similar in subjects with a body weight < 100 kg compared with the group with a body weight ≥ 100 kg (14% vs. 9% for the combined Q2W and Q4W groups). The increased frequency of injection site reactions in the combined Q2W and Q4W groups did not result in an increase in discontinuations in either the plaque psoriasis, the psoriatic arthritis or the axial spondyloarthritis studies.
Infections: In the placebo-controlled period of the phase III clinical studies in plaque psoriasis, infections were reported in 27.2% of patients treated with Taltz for up to 12 weeks compared with 22.9% of patients treated with placebo.
The majority of infections were non-serious and mild to moderate in severity, most of which did not necessitate treatment discontinuation. Serious infections occurred in 13 (0.6%) of patients treated with Taltz and in 3 (0.4%) of patients treated with placebo (see Precautions). Over the entire treatment period infections were reported in 52.8% of patients treated with Taltz (46.9 per 100 patient years).
Serious infections were reported in 1.6% of patients treated with Taltz (1.5 per 100 patient years).
Infection rates observed in psoriatic arthritis and axial spondyloarthritis clinical studies were similar to those observed in the plaque psoriasis studies with the exception of the frequencies of the adverse reactions of influenza and conjunctivitis which were common in patients with psoriatic arthritis.
Laboratory assessment of neutropenia and thrombocytopenia: In plaque psoriasis, 9% of patients receiving Taltz developed neutropenia. In most cases, the blood neutrophil count was ≥1,000 cells/mm³. Such levels of neutropenia may persist, fluctuate or be transient. 0.1% of patients receiving Taltz developed a neutrophil count <1000 cells/mm³. In general, neutropenia did not require discontinuation of Taltz. 3% of patients exposed to Taltz had a shift from a normal baseline platelet value to <150,000 platelet cells/mm³ to ≥75,000 cells/mm³. Thrombocytopenia may persist, fluctuate or be transient.
The frequency of neutropenia and thrombocytopenia in psoriatic arthritis and axial spondyloarthritis clinical studies is similar to that observed in the plaque psoriasis studies.
Immunogenicity: Approximately 9-17% of adult plaque psoriasis patients treated with Taltz at the recommended dosing regimen developed anti-drug antibodies, the majority of which were low titres and not associated with reduced clinical response up to 60 weeks of treatment. However, approximately 1% of patients treated with Taltz had confirmed neutralising antibodies associated with low drug concentrations and reduced clinical response.
In psoriatic arthritis patients treated with Taltz at the recommended dosing regimen up to 52 weeks, approximately 11% developed anti-drug antibodies, the majority of which were low titre, and approximately 8% had confirmed neutralising antibodies. No apparent association between the presence of neutralising antibodies and impact on drug concentration or efficacy was observed.
In paediatric psoriasis patients treated with Taltz at the recommended dosing regimen up to 12 weeks, 21 patients (18%) developed anti-drug antibodies, approximately half were low titer and 5 patients (4%) had confirmed neutralizing antibodies associated with low drug concentrations. There was no association with clinical response or adverse events.
In radiographic axial spondyloarthritis patients treated with Taltz at the recommended dosing regimen up to 16 weeks, 5.2% developed anti-drug antibodies, the majority of which were low titer, and 1.5% (3 patients) had neutralising antibodies (NAb). In these 3 patients, NAb-positive samples had low ixekizumab concentrations and none of these patients achieved an ASAS40 response. In non-radiographic axial spondyloarthritis patients treated with Taltz at the recommended dosing regimen for up to 52 weeks, 8.9% developed anti-drug antibodies, all of which were low titer; no patient had neutralising antibodies; and no apparent association between the presence of anti-drug antibodies and drug concentration, efficacy, or safety was observed.
Across all indications, an association between immunogenicity and treatment emergent adverse events has not been clearly established.
Paediatric population: The safety profile observed in children with plaque psoriasis treated with Taltz every 4 weeks is consistent with the safety profile in adult patients with plaque psoriasis with the exception of the frequencies of conjunctivitis, influenza, and urticaria which were common. Inflammatory bowel disease was also more frequent in paediatric patients, although it was still uncommon. In the paediatric clinical study, Crohn's disease occurred in 0.9% of patients in the Taltz group and 0% of patients in the placebo group during the 12-week, placebo-controlled period. Crohn's disease occurred in a total of 4 Taltz treated subjects (2.0%) during the combined placebo-controlled and maintenance periods of the paediatric clinical study.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.