One-third tapering demonstrated little to no effect on secondary indicators, but tapering by two-thirds resulted in substantial worsening of several clinical secondary outcomes, including joint count, C-reactive protein, and erythrocyte sedimentation rate. Patient-reported secondary outcomes (including Health Assessment Questionnaire, EuroQol 5-dimension scale, and visual analogue scale) remained unaffected in both the 33% or 66% taper groups.
A total of 34 patients (21 from the 33% group and 13 from the 66% group) who tapered in the first phase were able to completely stop using their biologic over the course of the second phase. Of these subjects, 38% experienced flares. Patients taking adalimumab fared better than those on etanercept, with 33% vs 53% experiencing flares (P =.050).
The authors reported a total of 443 adverse events, with 4% of patients experiencing a serious complication. Half of all adverse events involved the musculoskeletal system. No relationship was established between tapering protocols and adverse events.
Strengths of the OPTTIRA trial, identified by the authors, included involving a range of patients with RA at multiple centers, allowing for generalization of the study, and studying 2 different tapering strategies with 2 medications.
The researchers acknowledged that a challenge for clinicians going forward would be to identify patients for whom this tapering strategy is likely to be successful. Still, the results clearly indicate that for suitable candidates, clinicians and patients alike can expect good effect without loss of clinical response when adhering to a 33% tapering strategy of TNFi therapies. The same cannot be said, however, for the 66% strategy, which should therefore be avoided because of a significant effect on flares.
The researchers concluded, “We consider there is sufficient evidence for clinicians to reduce TNF inhibitor doses in some treatment responders.” Clearly, such reductions should be guided by a low level of disease activity and demonstrated good response on TNFi and DMARD therapies. For those patients who fit these inclusion criteria, lowering TNFi therapy by one-third (with an eye on complete discontinuation for some) may be a treatment strategy that offers significant symptom relief while being more cost-effective than continuing to receive standard maintenance dosages.
- The study was of short duration
- The study was not blinded
- Only 2 medications were assessed
- The study was performed solely on good responders
- Few participants were included
Ibrahim F, Lorente-Cánovas B, Doré CJ, et al. Optimizing treatment with tumour necrosis factor inhibitors in rheumatoid arthritis—a proof of principle and exploratory trial: is dose tapering practical in good responders? [published online August 17, 2017]. Rheumatology. doi: 10.1093/rheumatology/kex315