GENEVA, Switzerland—Switching patients with rheumatoid arthritis (RA), who show inadequate response to one or more tumor necrosis factor (TNF) inhibitors, to rituximab (RTX) (Rituxan®, Genentech/Biogen Idec) may be more efficacious than switching patients to an alternative anti-TNF agent, according to a new observational study in the May issue of Arthritis & Rheumatism.¹

"These results suggest that rituximab should be considered early as a therapeutic alternative after a first or second inadequate response to anti-TNF agents, rather than using all other alternative TNF agents," conclude researchers led by Axel Finckh, MD, with the rheumatology division at the University Hospital of Geneva, in Switzerland.

The researchers compared the effectiveness of switching to an alternative anti-TNF agent versus initiating therapy with RTX among 116 RA patients who showed an inadequate response to at least one TNF-blocker. Fifty patients received one cycle of RTX, and 66 patients were treated with a second or a third alternative anti-TNF agent.

RTX trumps alternate TNF-blocker

At baseline, there were no significant differences between the two groups, but patients in the RTX group showed greater improvements on the Disease Activity Score 28 (DAS28), compared with their counterparts taking an alternative TNF-blocker (P = .01). At 6 months, the mean decrease in DAS28 was -1.61 among patients who received RTX and -0.98 among patients who received an alternative TNF-blocker. RA patients treated with RTX also showed a reduction both in the number of tender joints and in the erythrocyte sedimentation rate (ESR) compared with RA patients who received an alternative anti-TNF agent.

Both treatments showed similar safety profiles. There were more dermatological complications, namely, injection site reactions in the anti-TNF group and more allergic complications, namely, mild-to-moderate infusion reactions in the RTX group, the study found.

Missing data on remission weakens strength of conclusion

"Despite the observational, uncontrolled nature of the study and the relatively high amount of missing data, the study does suggest, at minimum, that patients refractory to an anti-TNF agent experience a significant decline in disease activity with both switching to another anti-TNF agent, as well as switching to rituximab," Eric Matteson, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, told CIAOMed.

However "the magnitude of improvement is somewhat greater in the patients receiving rituximab
than those switched to another anti-TNF drug, which does reach statistical significance," he said.
 
"What we do not learn from this study, unfortunately, is how many of the patients who were switched went from high to moderate and especially low disease activity as assessed by the DAS, and how many went into remission by DAS [<2.6]," Dr. Matteson pointed out. "If the percentage of patients, for example, going into remission using either strategy are close or the same, a strategy of using a second anti-TNF agent is certainly justified when the first has failed to achieve acceptable disease control/remission," he advised.
 
"Since perhaps 30% to 40% of patients who fail an initial anti-TNF agent may respond to the second, and the responses are relatively prompt, within 4 to12 weeks, use of a second anti-TNF agent is certainly justified especially in patients who have articular disease without severe extra-articular involvement, such as vasculitis, before considering the use of a B-cell depleting drug," he said. "The use of other biologic response modifiers, such as anakinra [Kineret®], abatacept [Orencia®], and anti-B-cell agents like rituximab should be considered in patients with RA who develop severe systemic disease, such as vasculitis, and those with continued high or persistent moderate disease activity."

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Reference

1.Finckh A, Ciurea A, Brulhart L, et al. B cell depletion may be more effective than switching to an alternative anti-tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti-tumor necrosis factor agents. Arthritis Rheum. 2007;56:1417-1423.