Comparative Risk of Harm Associated With the Use of Targeted Immunomodulators: A Systematic Review

Abstract

ObjectiveTo systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).MethodsWe searched electronic databases through July 2015 to retrieve randomized controlled trials (RCTs) and observational studies comparing AEs between 2 or more TIMs head‐to‐head. We reported on the following outcomes: number of AEs, discontinuation due to AEs, serious AEs, mortality, serious infections, tuberculosis, herpes zoster, and malignancies. We qualitatively synthesized the literature and conducted random‐effects meta‐analyses if 3 or more studies provided data for an outcome.ResultsTen head‐to‐head RCTs and 51 observational studies were included in this systematic review. A majority of the studies (70%) were conducted in RA patients. Risk of treatment discontinuation due to AEs was higher with infliximab than with adalimumab or etanercept in RA, PsA, and AS. A higher risk for serious infections was noted with infliximab than with abatacept, adalimumab, or etanercept in RA. Risk for treatment discontinuation due to AEs, serious infections, and tuberculosis was lower with etanercept than with adalimumab in RA. Limited evidence suggested no comparative differences in risk for mortality, malignancies, and herpes zoster for adalimumab, etanercept, and infliximab in RA.ConclusionImportant differences were noted in the safety profile of TIMs in RA, generally favoring abatacept, adalimumab, and etanercept over infliximab. Head‐to‐head comparative evidence for other TIMs and non‐RA populations was insufficient to draw conclusions for most of the safety outcomes.

Eight-year survival study of first-line tumour necrosis factor α inhibitors in rheumatoid arthritis: real-world data from a university centre registry

“…These observations are confirmed by other Greek studies [11, 18, 19]. In line with our results, a recent systematic review highlighted that the risk of treatment discontinuation due to adverse events was greater for infliximab than for adalimumab or etanercept in RA patients [22]. The same review revealed a greater risk for serious infections with infliximab than with the other two therapeutic choices, while we showed that rates of serious infections did not differ statistically among the three drugs.…”

An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data

“…Increased rates of SIEs are an acknowledged risk of medications that have an immunomodulatory effect, including tofacitinib and bDMARDs [31,34,35]. The IRs for SIEs in the tofacitinib dose-comparison cohort (1.3 and 2.0 for patients with PsA receiving tofacitinib 5 and 10 mg BID, respectively) and in the all-tofacitinib comparison cohort (1.4) were consistent with the IR of 2.7 reported for tofacitinib in patients with RA who participated in phase I, II, III, and LTE studies [31] and 1.9 in patients with psoriasis in phase III and LTE studies [32].…”

Biological treatment for psoriasis and the risk of herpes zoster: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR)

“…In rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), data regarding the association of HZ and treatment with tumor necrosis factor (TNF) inhibitors are contradictory (6). Recent observational studies reported that treatment with TNF inhibitors is associated with increased risk for HZ (7)(8)(9)(10)(11)(12) and more severe HZ disease (13,14).…”