There have been a number of trials looking into the tapering of RA therapy. Some of these trials were rather flawed in concept, whereby patients who had achieved lower disease activity were tapered to lower doses, and then all RA therapy was withdrawn completely. This seems to arise from a fallacious concept and one that is not advocated by current American College of Rheumatology (ACR) or European League Against Rheumatism (EULAR) guidelines. That is, it is fallacious to believe that we can take someone with a chronic autoimmune systemic disease such as RA, where the memory B cells persist even after a remission has been induced, and withdraw all medication without inviting long-term problems. 

Current ACR and EULAR treatment recommendations advise to cautiously taper bDMARD therapy in patients with RA who achieve stable clinical remission on bDMARD therapy. However, most patients do not maintain remission or low disease activity after tapering or discontinuing biologic therapy. And, if you withdraw all therapy, virtually 90% to 95% of patients will have a flare within 1 to 2 years. Further, despite advances in the treatment of RA over recent decades, most patients with RA do not achieve remission or full physical function. There was an interesting presentation by Myasoedova and colleagues at EULAR 2018 showing a substantial and growing functional disability burden, despite recent advances in controlling RA disease activity. So, I think that it is important to keep these things in mind.

The challenge is to find a lower-intensity regimen that keeps people in remission over the long-term. That is likely the next level of studies that we will be interested in. There are strategies and potential successes with either lowering conventional DMARD medication doses (eg, with methotrexate as the anchor drug) or reducing the frequency of the biologic medication. There are also instances in which patients with RA, for various reasons, may be good candidates for biologic monotherapy, whereby no concomitant methotrexate or conventional DMARD is given. In these cases, biologic monotherapy may achieve a better response and lower levels of disease activity than would be the case with conventional DMARD monotherapy (eg, methotrexate). Adherence is a key issue here, as many patients prefer not to take methotrexate and/or other conventional DMARDs. And without adherence, there is a much lesser chance of optimal disease control.

A Cochrane Database of Systematic Reviews study by van Herwaarden and colleagues captured many of the limitations that we face with respect to the current data. None of the included studies on bDMARD tapering assessed long-term safety and costs, even though these are key factors clinicians would consider when deciding to taper therapy. Additionally, the authors called for future trials to address current gaps to include assessments of function and radiographic outcomes after longer follow-up; assessment of long-term safety, cost-effectiveness and predictors for successful down-titration; use of a validated flare criterion; use of noninferiority trial designs; and an investigational approach to tapering guided by disease activity measures rather than by fixed, reduced doses.