Among patients seropositive for rheumatoid arthritis (RA) who were biologic-naïve, rituximab treatment was found to be as clinically effective as but more cost-saving than tumor necrosis factor (TNF) inhibitor treatment. These results were recently published in The Lancet.
In prior studies, TNF inhibitors and rituximab had similar efficacy in treating patients with RA who had not responded to non-biologic disease modifying anti-rheumatic drugs (nbDMARDs), although no head-to-head trials had been conducted until this trial. Since biologic agents are costly, choice of treatment must weigh expense against potential benefit. Treatment with rituximab, which is only approved for TNF inhibitor-refractory RA, has a lower yearly cost than treatment with a TNF inhibitor in the United Kingdom. The authors compared the efficacy and cost of rituximab treatment with that of TNF inhibitor treatment in Optimal Management of Rheumatoid Arthritis Patients Requiring Biologic Therapy (ORBIT, ClinicalTrials.gov Identifier NCT01021735), an open-label randomized trial.
Researchers enrolled 295 patients with active RA who were seropositive for anti-cyclic citrullinated peptide antibodies or rheumatoid factor (or both), had failed treatment with 2 or more nbDMARDs, and had not previously been treated with biologics. Participants received intravenous rituximab (n=144, 1 g every 2 weeks for 2 doses, and after 26 weeks if disease activity persisted) or TNF inhibitor treatment (n=151, adalimumab 40 mg subcutaneously every other week or etanercept 50 mg subcutaneously every week).
Patients who did not respond or were intolerant to the assigned treatment had the option to switch to the other treatment arm.
At 12 months, the change in 28 joint count disease activity score-erythrocyte sedimentation rate (DAS28-ESR) from baseline for the rituximab group was similar to that of the TNF inhibitor group (-2.6 vs -2.4, respectively). The difference between the groups was -0.19, which fell within the prespecified noninferiority margin of 0.6 DAS28-ESR units.
Treatment with rituximab was less costly than treatment with TNF inhibitors (£9405 vs £11 523 per patient; P < .0001). It should be noted, however, that switching from a TNF inhibitor to rituximab occurred more frequently than switching from rituximab to a TNF inhibitor (32% vs 19% of patients switched treatments, respectively; P = .008).
Overall, 95% of patients in each group experienced adverse events. More patients receiving rituximab had diarrhea than those receiving a TNF inhibitor (P = .03). Injection site reactions were more common in the TNF inhibitor group (P = .003). The rate of serious adverse events was similar for both groups (15 patients receiving rituximab vs 12 patients receiving TNF inhibitors; P = .5462), with no cases of progressive multifocal encephalopathy noted in either treatment group.
Summary and Clinical Applicability
ORBIT is the first randomized controlled trial to directly compare rituximab with TNF inhibitors in patients with biologic-naïve, seropositive RA who have failed nbDMARDs therapy. Rituximab treatment was clinically noninferior to, and more cost-effective, than TNF inhibitor treatment.
“In the UK, widespread adoption of a rituximab strategy, in preference to TNF inhibitor treatment, would translate into substantial budgetary savings for health services with no measurable loss of efficacy,” the authors stated.
Limitations and Disclosures
- Radiographic outcomes were not measured, so whether radiographic joint damage outcomes differed between rituximab and TNF inhibitor strategies is unknown
- Patients with seropositive RA are known to have a slightly greater response to rituximab than seronegative patients, so these results cannot be generalized to patients with seronegative RA
- Study follow-up period was limited to 1 year, precluding any conclusions regarding long-term effects on disease progression
Roche provided the study drug rituximab and funded the collection of a parallel biobank, but had no role in the study design, conduct, data analysis, or reporting of results.
Several authors report financial relationships with various pharmaceutical companies. A full list of disclosures is available in the journal site.
Porter D, van Melckebeke J, Dale J, et al. Tumour necrosis factor inhibition versus rituximab for patients with rheumatoid arthritis who require biological treatment (ORBIT): an open-label, randomised controlled, non-inferiority, trial. Lancet. 2016;388:239-47.