Five-year Safety Data from 5 Clinical Trials of Subcutaneous Golimumab in Patients with Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

Abstract

OBJECTIVE: Assess 5-year golimumab (GOL) safety in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). METHODS: Subcutaneous (SC) GOL (50 mg or 100 mg every 4 weeks) was evaluated in phase 3 trials of patients with active RA, PsA, and AS. Safety data through Year 5 were pooled across 3 RA trials [1 each evaluating methotrexate (MTX)-naive, MTX-experienced, and antitumor necrosis factor (TNF)-experienced patients], 1 PsA trial, and 1 AS trial. Data summarized was derived from both placebo-controlled (through weeks 24-52) and uncontrolled study periods. For adverse events (AE) of special interest [serious infections (SI), opportunistic infections (OI), deaths, malignancies, demyelination, tuberculosis (TB)], incidence per 100 patient-years (pt-yrs) was determined. RESULTS: Across all trials, 639 patients received placebo and 2228 received SC GOL 50 mg only (n = 671), 50 mg and 100 mg (n = 765), or 100 mg only (n = 792). Safety followup extended for averages of 28.5 and 203.2 weeks for placebo and GOL, respectively. Respective placebo and GOL AE incidence/100 pt-yrs (95% CI) through Year 5 were 4.86 (2.83-7.78) and 3.29 (2.92-3.69) for SI, 0.00 (0.00-0.86) and 0.23 (0.14-0.35) for TB, 0.00 (0.00-0.86) and 0.22 (0.13-0.34) for OI, 0.00 (0.00-0.86) and 0.10 (0.05-0.20) for lymphoma, 0.00 (0.00-0.86) and 0.08 (0.03-0.17) for demyelination, and 0.29 (0.01-1.59) and 0.41 (0.29-0.57) for death. TB, OI, lymphoma, and demyelination incidence appeared to be higher among patients receiving GOL 100 mg only. CONCLUSION: SC GOL safety through Year 5 remained consistent with previously reported Year 3 findings and with other TNF antagonists. Numerically higher incidences of TB, OI, lymphoma, and demyelination were observed with 100 mg versus 50 mg. Clinicaltrials.gov identifiers: NCT00264537 (GO-BEFORE), NCT00264550 (GO-FORWARD), NCT00299546 (GO-AFTER), NCT00265096 (GO-REVEAL), and NCT00265083 (GO-RAISE)

Lymphoma in the Tofacitinib Rheumatoid Arthritis Clinical Development Program

“…In this analysis of lymphoma events occurring during the tofacitinib RA clinical development program, IRs for lymphoma were stable over time, which was consistent with the findings of an integrated analysis of all malignancies occurring in the tofacitinib RA program . The IR for lymphoma in the tofacitinib RA program was similar to rates observed in long‐term clinical studies of patients with RA treated with the biologic DMARDs adalimumab , certolizumab pegol , infliximab , abatacept , and golimumab , where IRs ranged from 0.05–0.16 patients with events per 100 patient‐years. The SIR of lymphoma calculated for tofacitinib based on comparison against the US SEER database was within range of SIRs observed in these clinical studies of biologic therapies (SIRs ranged from 1.81–6.40; see Figure ) , although comparison should be made with caution, owing to variability in the study designs and patient populations analyzed in these studies.…”

“…The IR for lymphoma in the tofacitinib RA program was similar to rates observed in long‐term clinical studies of patients with RA treated with the biologic DMARDs adalimumab , certolizumab pegol , infliximab , abatacept , and golimumab , where IRs ranged from 0.05–0.16 patients with events per 100 patient‐years. The SIR of lymphoma calculated for tofacitinib based on comparison against the US SEER database was within range of SIRs observed in these clinical studies of biologic therapies (SIRs ranged from 1.81–6.40; see Figure ) , although comparison should be made with caution, owing to variability in the study designs and patient populations analyzed in these studies. SIRs for lymphoma were also consistent with rates observed in meta‐analyses and observational studies of biologic DMARDs for the treatment of RA, where SIRs for lymphoma ranged from 1.7–5.99 .…”

“…Standardized incidence ratios of lymphoma with tofacitinib clinical trials compared with published clinical trials data for biologic disease‐modifying antirheumatic drugs used to treat rheumatoid arthritis. Clinical trials data for tofacitinib, adalimumab , certolizumab pegol , etanercept , infliximab , abatacept , and golimumab are standardized against the Surveillance, Epidemiology, and End Results ( SEER ) program database . For golimumab, combined data for 50‐mg and 100‐mg dose groups are shown.…”

Golimumab for the treatment of ulcerative colitis

“…In the same way, the overall time-adjusted incidence of malignancy was not higher with golimumab than placebo (1.07 vs. 2.59 per 100 patient-years). By contrast, higher tuberculosis, lymphoma, and demyelination rates were observed with golimumab versus placebo, although this risk level appeared to be higher only in patients receiving 100 mg golimumab [23]. …”

A Review on Golimumab in The Treatment of Psoriatic Arthritis

“…Golimumab was demonstrated to be generally safe and well tolerated in first in human clinical trials. The phase III pivotal clinical trials including RA, PsA and AS patients; [4,6,7,[9][10][11][12][13][14][15]43] showed the adverse events (AEs) profile across these populations seem to be comparable to other anti-TNFs [19,23,32,38,[44][45][46][47] During the first in human clinical trial the observed AEs were mild to moderate in intensity and had no clear dose-related trend in the incidence of AEs among golimumab dose cohorts (excluding headaches). The presence of anti-golimumab antibodies did not correlate with the incidence of AEs.…”