Patients with RA, PsA,[18,19] and AS[20,21] typically require life-long treatment; therefore, long-term safety is an important consideration for both health care providers and patients when selecting treatment. In these pooled analyses, we combined the safety results of the TNFi IV golimumab 2 mg/kg from three phase 3 studies, GO-FURTHER (RA), GO-VIBRANT (PsA), and GO-ALIVE (AS). The proportion of patients who completed the safety follow-up (through week 112 in the RA trial and week 60 in the PsA and AS trials) was relatively high (86%), resulting in a total of 1697 PY of exposure. During these trials, IV golimumab was generally well-tolerated, and AEs were consistent with the known safety profile of other TNFi, including subcutaneous golimumab.[9,11,13,14,22]
During the placebo-controlled periods, SAEs were uncommon in both the placebo group (2.4%) and the combined golimumab group (3.8%). Infections were the most common type of AE in the pooled results, which was consistent with the results reported individually from each of these studies. The incidence of serious infections per 100 PY was highest in the RA trial, followed by the PsA and AS trials; the pooled incidence of 3.4 serious infections per 100 PY in all golimumab-treated patients was comparable to that reported for other TNFi agents.[23–25] Other AEs of interest, including malignancy, MACE, opportunistic infections, and uveitis, were also uncommon through the end of the trials. Malignancy occurrence was comparable between placebo (0.4%) and golimumab (0.1%) during the placebo-controlled periods; no cases of lymphoma were reported through trial completion. While a small number of golimumab patients (n = 6 [0.4%]) acquired active TB in countries where TB is endemic (Argentina, Lithuania, Malaysia, Mexico, and Ukraine), no case of latent TB converted to active TB.
Among the three studies, AEs tended to be more common in patients with RA, with infections being the most common class of AE reported. Previous analyses of patients receiving TNFi have shown a higher incidence of serious infections in RA patients than in patients with AS or PsA.[26,27] In the current study, patients in the RA study were, on average, older and had longer disease duration and were more likely to be receiving concomitant corticosteroids relative to patients in the PsA and AS studies. These factors have been previously associated with an increased risk of serious infection among RA patients treated with TNFi. In addition, concomitant MTX use was required in the RA trial, but not in the other trials. In the PsA and AS trials, there was no clear pattern of differences in the rate of SAEs or serious infections between patients who were receiving concomitant MTX and those who were not. Elevations in ALT were more frequent in patients receiving concomitant MTX in the PsA trial, which was not unexpected considering that hepatic toxicity is commonly observed with MTX therapy. This pattern was not seen in the AS trial, although the proportion of patients receiving MTX in that trial was considerably lower.
Fewer than 3% of all golimumab-treated patients had an infusion reaction; none was serious or severe. Approximately 22% of patients treated with golimumab developed antibodies to golimumab, although only 6% of patients tested positive for neutralizing antibodies. The proportion of patients with antibodies to golimumab and neutralizing antibodies was numerically lower in patients who received concomitant MTX than in those who received golimumab monotherapy; however, interpretation of these results is limited by the lack of a golimumab monotherapy population in the RA study and the relatively small number of patients receiving golimumab+MTX in the AS study. Infusion reactions were more common in patients with antibodies to golimumab than those without antibodies to golimumab.
Oral corticosteroid use has been associated with an increased risk of serious infections in patients with RA, even with doses ≤ 5 mg/day (prednisone or equivalent). In the current pooled analyses, the proportions of patients with a serious infection during the placebo-controlled periods were numerically higher in patients receiving concomitant oral corticosteroids compared with patients not receiving these medications in both the placebo and golimumab groups. Among all golimumab-treated patients, the number of serious infections per 100 PY through study completion was similar for patients who did and did not receive oral corticosteroids. Previous research has shown that the highest risk of serious infection with TNFi tends to be within the first 6 months of treatment, and the risk of serious infections associated with corticosteroids is dose-dependent. The mean corticosteroid dose in the treatment groups across the three trials ranged from 6.1 to 7.9 mg/day (prednisone or equivalent), although patients could have received doses up to 10 mg/day. Also, it should be noted that there may have been imbalances in age, disease duration, and concomitant medication use between the patients who did and did not receive concomitant corticosteroids, as the studies were not designed to compare outcomes by corticosteroid use.
With data from over 700 golimumab-treated patients and approximately 71 patient-years of follow-up, these results represent the largest pooled analysis, to date, from phase 3 studies of IV golimumab in patients with RA, PsA, and AS. The studies included in the current analysis were limited to 1 or 2 years in duration, and the studies were not powered to detect rare events. Differences in study design also limited some of the analyses on concomitant medications. However, the totality of the pooled data across three rheumatologic indications demonstrated consistency with each of the individual trials.
Arthritis Res Ther. 2022;24(73) © 2022 BioMed Central, Ltd.
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