Rheumatoid arthritis patients who fail initial tumor necrosis factor–inhibitor treatment may do a bit better when switched to rituximab instead of another anti-tumor necrosis factor agent, according to findings from an open-label, prospective study.
In the SWITCH-RA trial, investigators enrolled 405 rheumatoid arthritis (RA) patients who switched to the anti-CD20 B-cell-depleting drug rituximab (Rituxan) after they didn’t respond to or couldn’t tolerate their first tumor necrosis factor inhibitor (TNFi) and 323 RA patients in the same situation who switched instead to a second TNFi (Ann. Rheum. Dis. 2014 Jan. 17 [doi:10.1136/annrheumdis-2013-203993]).
Dr. Paul Emery
After 6 months, the rituximab group had a mean improvement of –1.5 points on the 10-point and 28-joint RA Disease Activity Score, calculated with erythrocyte sedimentation rate (DAS28-3–ESR), after controlling for baseline characteristics and disease activity.
The group that switched to a second TNFi improved by a mean of –1.1 points (P = .007). The patients who received rituximab were sicker at baseline than those who started a second TNFi (mean DAS28-3–ESR of 5.2 vs. 4.8 points, respectively). The investigators didn’t name the TNFi agents to which patients were switched.
The results "provide evidence from real-world practice" that patients "achieve significantly better clinical responses over 6 months if they receive rituximab rather than an alternative TNF inhibitor as their second biological therapy," said Dr. Paul Emery of the University of Leeds (England) and his associates.
The findings support rituximab’s current Food and Drug Administration RA indication for use with methotrexate in adults who don’t do well on TNF inhibitors.
In a subanalysis of the data, rituximab kept its statistical edge only when used in seropositive subjects, who made up about 80% of the study population. Although seronegative patients showed improvements at 6 months, "there was no significant difference between the rituximab and alternative TNF inhibitor groups." Due to the low number of seronegative patients, the project was "underpowered to detect small differences," but the findings also jibe with "recent studies reporting enhancement of clinical responsiveness to rituximab in seropositive" patients, the investigators said.
In a second subanalysis, rituximab kept its edge only in those who quit initial TNFi therapy because it didn’t work and not in those who couldn’t tolerate it.
That makes sense because, when the first TNFi doesn’t work, it’s probably because patients don’t have TNF-alpha–mediated disease. When its power fades over time, most likely it means that patients have developed antibodies to it. In both situations, a biologic with a different mechanism of action, like rituximab, is probably the best choice, Dr. Emery and his associates said.
Study subjects were from Europe, South America, and Canada. Most were middle-aged women with RA for about 8 years who had been on their first TNFi for about 2 years.
Pneumonia was diagnosed in 0.7% of rituximab and 0.2% of second-TNFi patients. Urinary tract infections were diagnosed in 0.7% of rituximab patients but no second-TNFi patients. One TNFi patient tested positive for tuberculosis but did fine with prophylactic treatment, they noted.
Two TNFi patients were diagnosed with new-onset squamous cell carcinomas. One rituximab patient developed prostate cancer and another Waldenstrom’s macroglobulinemia.
Hoffmann-La Roche makes rituximab and paid a third party to write up the results. Dr. Emery advises and runs studies for Roche and other companies marketing drugs for RA. Three of the other 14 investigators are Roche employees, and most of the rest have financial ties to the company.