An estimated one-third of rheumatoid arthritis patients don’t experience long-lasting benefits from the first tumor necrosis factor (TNF) inhibitor that they take. The question when the first biologic doesn’t work is: What next? Rheumatologists used to be fairly evenly divided between prescribing another TNF inhibitor and trying a different drug class. New research, from U.K. scholars, suggests that patients ought to try a new kind of drug following a failed first TNFi.

“RA patients who failed the first TNFi should receive BDMA (Biologics with Different Mode of Action),” Muhammad Shipa and colleagues wrote in a paper presented as a poster at the recent British Society of Rheumatology annual meeting.

To test the efficacy of second TNFi and other drugs, the researchers analyzed data from 211 patients. There were three times the number of women as men in the study, and the average age was just in the low 60s. Researchers measured at least moderate responses from treatment six months out. The breakdown of patients was as follows:

  1. 1. Among the 97 patients who tried a second TNFi, 38 percent experienced at least a moderate response.
  2. Of the 114 who used different kinds of drugs — 53 took rituximab, 30 took abatacept, and 31 took tocilizumab — 75 percent achieved at least moderate responses.
  3. Those percentages held for both seropositive patients (who had antibodies) and for seronegative patients (no antibodies). For seropositive patients, 34 percent of those who took a second TNFi and 72 percent of those who used a different drug saw at least moderate responses. And among seronegative patients, those percentages were 38 and 73 respectively.
  4. The rates for the three other kinds of drugs were also similar: 77 percent (rituximab), 73 percent (abatacept), and 74 percent (tocilizumab).
  5. There were different response rates between seronegative and seropositive patients, however, when it came to the other drugs. For seropositive patients, rates were positive for rituximab (88 percent) and tocilizumab (76 percent), but not for abatacept (36 percent). The story was flipped for seronegative patients, who responded well to abatacept (95 percent), and less so to tocilizumab (71 percent), and considerably less to rituximab (41 percent).
  6. “Of note,” observes MedPage, “tocilizumab performed about equally well regardless of serostatus.”

“From the results of this study, we suggest to start biologics of a different mode of action for secondary-failure patients instead of using a second TNF inhibitor,” Dr. Shipa said. “For the seropositive group, we should consider rituximab or tocilizumab, and for the seronegative group, abatacept or tocilizumab.”

Prior research shows much less promising, adverse outcomes for “non-medical switching”. Click here to read about the degree to which patients can safely switch from biologics to biosimilars.

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