Cycling TNF Treatments in Psoriatic Arthritis Reduces Efficacy

A review of 18 studies concludes that switching psoriatic arthritis patients who have stopped responding to one tumor necrosis factor inhibitor (TNFi) to another medication in the same class will likely reduce their symptoms, but the initial effectiveness of each new medication will likely be less than the initial effectiveness of the former medication.

“First-line therapy yielded better results compared with second-line therapy, and significant differences were observed between second- and third-line TNFi treatments,” the study authors wrote in Clinical Rheumatology. “More research is needed to quantify the effectiveness of sequential anti-TNF lines in this progressive population‚ and to compare these effects with responses to drugs with different mechanisms of action.”

The authors of the new review noted that relatively few prior studies have evaluated the relative effectiveness of earlier and later lines of TNFi therapy.

Only a single study, moreover, used multivariate analysis to evaluate what factors made some patients respond better than others to multiple different TNFi medications. That study, an analysis of a Danish registry, found that patients were less likely to respond to a second course of TNFi treatment (i.e. achieve a 20% or 50% reduction of symptoms as defined by criteria from the American College of Rheumatology) if safety, rather than lack of effect, caused them to switch (odds ratio [OR] 0.04; p = 0.003 and OR 0.05; p = 0.03, respectively).

Researchers have looked into the effects of switching among TNFi treatments in patients with all the major rheumatic diseases, and while most studies have concluded that new treatments can work when old treatments fail, their conclusions differ in many other respects.

A 2009 study published in the Annals of Rheumatic Disease compared the efficacy of switching to another TNFi or a different class of medication (rituximab) in rheumatoid arthritis patients who discontinued initial TNFi treatment, either because of side effects or ineffectiveness.

“When the motive for switching was ineffectiveness to previous TNFis, the longitudinal improvement in disease activity score (DAS28) was significantly better with rituximab than with an alternative TNFi (p = 0.03; at 6 months, −1.34 (95% CI −1.54 to −1.15) vs −0.93 (95% CI −1.28 to −0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for rituximab and alternative TNFis (p = 0.40),” the study authors wrote.

A 2015 study in Clinical Therapeutics, on the other hand, found that rheumatoid arthritis patients were typically better off trying another TNFi rather than a different type of medication if they stopped responding to initial TNFi treatment.

“After adjusting for baseline differences, patients who switched to second TNFis versus a non-TNF incurred lower RA-related costs ($20,938.9 vs $22,645.2; P = 0.0010) and total health care costs ($34,894.6 vs $38,437.2; P = 0.0010) 1 year post switch. These differences were driven by increased physician office visit costs among the non-TNF group,” the study authors wrote.

Studies that have tried to define what level of side effects or insufficient effectiveness should merit a switch from a patient’s current treatment to some new treatment have also failed to reach any consistent conclusion.