Rituximab, tocilizumab better than abatacept in refractory rheumatoid arthritis
Treatment with rituximab or tocilizumab, compared with abatacept, leads to greater improvements in outcomes among adults with refractory rheumatoid arthritis (RA) at 2 years, a study has shown.
“These results apply to patients with longstanding and refractory RA who had previously received one or more biologics, and not biologic agent-naïve patients with shorter disease duration,” researchers said.
Average durations of survival without failure were 19.8, 15.6 and 19.1 months for rituximab, abatacept and tocilizumab, respectively. Rituximab (life expectancy difference without failure [LEDwf], 4.1; 95 percent CI, 3.1–5.2) and tocilizumab (LEDwf, 3.5; 2.1–5.0) showed greater average durations than abatacept, and there was substantial uncertainty about tocilizumab compared with ritxumab (LEDwf, –0.7; 1.9–0.5). [BMJ 2019;364:l67]
Furthermore, there was no evidence in terms of difference among treatments for mean duration of survival without death, presence of cancer or serious infections, or major adverse cardiovascular events.
“Serious adverse events did not differ between the three non-tumour necrosis factor-α biologics. Such events were more common in association with tocilizumab than with rituximab and abatacept. Therefore, the observed higher drug retention rate of rituximab and tocilizumab compared with abatacept is related to greater effectiveness rather than a better safety profile,” researchers said.
Nearly 30 percent of those using rituximab and tocilizumab and 60 percent of those using abatacept ceased treatment at month 24, highlighting the continued need for enlargement of the armamentarium of new biologic and targeted disease modifying antirheumatic drugs in RA treatment.
According to researchers, there are only a few comparative effective studies that examined the study drugs, but these studies had limited population samples, had discrepant results and compared disease activity in the short term. [Int J Rheum Dis 2016;19:1093-1102; Ann Rheum Dis 2011;70:1216-1222; Ann Rheum Dis 2014;73:909-912; Rheumatology (Oxford) 2016;55:230-236; Arthritis Res Ther 2016;18:280]
“Randomized clinical trials are the standard strategy for drug comparisons. However, although a few trials compared non-TNF biologics with anti-TNF agents, no randomized clinical trial has compared rituximab, abatacept and tocilizumab with each other, and probably no direct head-to-head randomized clinical trial will compare these drugs in the future,” they added. [Lancet 2013;381:1541-1550; Ann Rheum Dis 2014;73:86-94]
The present population-based prospective study included 3,162 adults (>18 years) with RA according to 1987 American College Rheumatology criteria, enrolled in one of three French Society of Rheumatology registries; who had no severe cardiovascular disease, active or severe infections, or severe immunodeficiency, with follow-up of at least 24 months.
Drug retention without failure at 24 months was the primary outcome. Failure was defined as all-cause death; discontinuation of rituximab, abatacept, or tocilizumab; initiation of a new biologic or a combination of conventional disease modifying antirheumatic drugs; or increase in corticosteroid dose >10 mg/d compared with baseline at two successive visits.
Treatment effects were presented as LEDwf, which measures the difference between average duration of survival without failure, because of nonproportional hazards.