Approximately 1 in 3 patients with rheumatoid arthritis (RA) who discontinued tofacitinib maintained low disease activity after 1 year. Low baseline rheumatoid factor (RF) correlated with continued low disease activity after tofacitinib discontinuation. These findings were published in Rheumatology.
While biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have demonstrated efficacy in RA, long-term safety concerns and cost may limit their use. Data show that tumor necrosis factor (TNF) inhibitors may be discontinued successfully without inducing disease flares. Until recently, however, there have been no studies examining outcomes following tsDMARD discontinuation.
Researchers evaluated whether low disease activity can be maintained in patients with RA who discontinued tofacitinib and sought to identify predictors of low disease activity after tofacitinib discontinuation.
Patients from a phase 3 and long-term extension study of tofacitinib were enrolled in this study if they had achieved low disease activity. Based on the decision of the treating physician and patient, tofacitinib was discontinued in 54 of 64 patients.
At 1 year, 37% of the 54 patients who discontinued tofacitinib remained free of tofacitinib and experienced no disease flares.
Low RF at baseline was associated with a higher likelihood of maintaining remission after discontinuing tofacitinib. Patients who remained tofacitinib-free at 1 year had lower RF titers than patients who had to restart tofacitinib (40.0 U/mL vs 113.3 U/mL; P =.02).
When low RF was defined as <32 U/mL, approximately 50% of patients with low RF and 20% with high RF were tofacitinib-free at 1 year.
Most patients (80%) for whom tofacitinib discontinuation failed were able to achieve low disease activity with rescue therapy of tofacitinib re-initiation or another DMARD.
Summary and Clinical Applicability
The use of tofacitinib for RA may be limited by its high cost and potential long-term safety risks. While bDMARDs have been successfully discontinued without provoking disease flares, doing the same with tofacitinib effectively has not been established. Researchers found that one-third of patients remain in remission after discontinuing tofacitinib and that low baseline RF titers predict low disease activity after tofacitinib discontinuation.
“Tofacitinib, although expensive, is very likely to become a first-line option for RA patients, especially if it is possible to discontinue treatment after use for a certain period of time. Accumulation of further evidence to identify candidate patients for tofacitinib discontinuation may help not only RA patients, but may contribute to reducing medical costs,” the researchers wrote.
Limitations and Disclosures
- Disease flares were not defined using uniform criteria and were determined based on the discretion of the investigator
- Since tofacitinib was discontinued based on the decision of the physician and patient, the study population may have reflected patients who were more likely to maintain low disease activity after tofacitinib discontinuation
The researchers report financial relationships with AbbVie, Chugai Pharmaceutical, Santen Pharmaceutical, Takeda Pharmaceutical, Astellas Pharma, AYUMI Pharmaceutical, Ono Pharmaceutical, Mitsubishi-Tanabe Pharma, Pfizer, Daiichi-Sankyo, Bristol-Myers Squibb, Astellas Pharma, Eisai Pharma, Janssen, Asahi-kasei, Eli Lilly, GlaxoSmithKline, UCB, Teijin, MSD, Taisho-Toyama, Kyowa-Kirin, Industrial Pharma, Nippon Shinyaku, and Actelion Pharmaceuticals.
Kubo S, Yamaoka K, Amano K, et al. Discontinuation of tofacitinib after achieving low disease activity in patients with rheumatoid arthritis: a multicentre, observational study [published online April 12, 2017]. Rheumatology (Oxford). doi:10.1093/rheumatology/kex068