Simponi 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 golimumab based on the comprehensive assessment of the available adverse event information. A causal relationship with golimumab 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.
Safety data from Phase 2 and 3 clinical trials are available from 6161 golimumab-treated patients including 3090 with rheumatoid arthritis, 634 with psoriatic arthritis, 768 with ankylosing spondylitis, 1245 with ulcerative colitis, 231 with severe persistent asthma, and 193 with active non-radiographic axial spondyloarthritis (nr-Axial SpA). Adverse reactions observed with golimumab are summarized in Table 30.
In general, the overall safety profile was similar for patients receiving golimumab via the SC or IV routes of administration.
Within the designated system organ classes, the adverse reactions are listed under headings of 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, including isolated reports), Not known (cannot be estimated from the available data). (See Table 30.)

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The data described as follows reflect adverse reactions from the SC Phase 2 and 3 clinical trials, except for administration reactions and liver enzyme elevations, which includes both SC and IV data. 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.
Infections (see Precautions): 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 patient-year: 0.61; 95% CI: 0.55, 0.67) compared with 11.0% of control patients (incidence per patient-year: 0.55; 95% CI: 0.46, 0.64). In controlled and uncontrolled portions of the studies with a median follow-up of approximately 4 years, the incidence per patient year of upper respiratory tract infections was 0.35 events; 95% CI: 0.34, 0.36, for golimumab-treated patients.
In the controlled period of pivotal trials, infections were observed in 23.0% of golimumab-treated patients (incidence per patient-year: 1.32; 95% CI: 1.23, 1.41) compared with 20.2% of control patients (incidence per patient-year: 1.22; 95% CI: 1.09, 1.36). In controlled and uncontrolled portions of the trials with a median follow-up of approximately 4 years, the incidence per patient-year of infections was 0.81 events; 95% CI: 0.79, 0.83, for golimumab-treated patients.
Serious infections observed in golimumab-treated patients included sepsis, pneumonia, cellulitis, abscess, opportunistic infections and tuberculosis. In the controlled period of RA, PsA, ulcerative colitis, 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 patient-year of follow-up in the controlled period of RA, PsA, AS, and nr-Axial SpA trials was 0.07; 95% CI: 0.05, 0.11 for the golimumab 100 mg group, 0.03; 95% CI: 0.01, 0.06 for the golimumab 50 mg group and 0.04; 95% CI: 0.02, 0.07 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. 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 patient-year of all serious infections was 0.04; 95% CI: 0.04, 0.05, in patients receiving golimumab 100 mg and 0.03; 95% CI: 0.02, 0.03, in patients receiving golimumab 50 mg. These results may be confounded by the designs of the pivotal trials and different durations of follow-up across treatment groups.
Malignancies (see Precautions): 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. These results may be confounded by the small number of events, designs of the Phase 3 studies, and different durations of follow-up across treatment groups. The majority of lymphomas occurred in RA Study 2, which enrolled patients previously exposed to anti-TNF agents who had longer disease duration and more refractory disease.
Malignancies other than lymphoma: In the controlled periods of pivotal trials, 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 an exploratory clinical trial involving patients with severe persistent asthma, more patients treated with golimumab had malignancies compared with control patients. The significance of this finding in the asthma population is unknown.
The potential role of TNF-blocking therapy in the development of malignancies is unknown.
Demyelinating disorders (see Precautions): 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. These results may be confounded by the small number of events, designs of the pivotal trials, and different durations of follow-up across treatment groups.
Liver enzyme elevations: In the controlled period of RA and PsA pivotal trials, mild ALT elevations (>1 and <3 x ULN) occurred in similar proportions of golimumab-treated and control patients (22.1% to 27.4% of patients); in the AS and nr-Axial SpA study, 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 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 (7.8% 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.
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. The majority of these elevations were asymptomatic. 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.
In the IV pivotal trials, liver enzyme elevations were comparable with those observed in the SC studies with the exception of the following: In the controlled period of the IV PsA pivotal trial, mild ALT elevations (> 1 and < 3 x ULN) were observed in more golimumab-treated patients (34%) than control patients (26%).
In the controlled period of the IV PsA pivotal trial, ALT elevations ≥ 3 and < 5 ULN were observed in more golimumab-treated patients (2.9%) than control patients (0.4%).
In the controlled period of the IV PsA pivotal trial, ALT elevations ≥ 5 x ULN were observed in more golimumab-treated patients (1.7%) than control patients (0.4%).
Administration reactions: In the controlled periods of the pivotal trials, 5.4% of golimumab-treated patients had injection site reactions compared with 2.0% in control-treated patients. The majority of the injection site reactions were mild and moderate and the most frequent manifestation was injection site erythema.
In the controlled periods of the pivotal IV trials, 0.2% of placebo-treated subjects and 2.8% of golimumab-treated subjects had an infusion reaction. The most common infusion reactions were rash and headache. No serious infusion reactions were reported.
In controlled phase 2 and/or 3 trials in RA, PsA, AS, nr-Axial SpA, severe persistent asthma, and Phase 2/3 trials in UC, no patients treated with golimumab developed anaphylactic reactions deemed to be related to golimumab.
Antinuclear antibodies (ANA)/anti-double-stranded DNA (dsDNA) antibodies: In the controlled and uncontrolled periods of the 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 titers 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% (see Precautions).
Postmarketing experience: The frequencies provided as follows reflect reporting rates of adverse reactions from the worldwide post-marketing experience with golimumab. Precise estimates of incidence cannot be made due to voluntary reporting from a population of uncertain size. These adverse reactions 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), and Not known (cannot be estimated from the available data). (See Table 31.)

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