In RA Remission? Halve the Xeljanz Dose


Reduction appeared preferable to total withdrawal in Japanese study
Nancy Walsh,08.12.2019 in MedPage


Dose reduction was feasible for patients with rheumatoid arthritis who achieved remission or low disease activity with tofacitinib (Xeljanz), and may be preferable to complete withdrawal because fewer disease flares occurred, Japanese researchers reported.


Among patients who were in remission or who had low disease activity after 1 year of tofacitinib, 5 mg twice per day, the incidence rates of flare were 0.73 (95% CI 0.43-1.22) per person-year for patients who discontinued the treatment, 0.44 (95% CI 0.25-0.77) per person-year among those who reduced the dose to 5 mg once per day, and 0.04 (95% CI 0.01-0.27) for those who continued on full doses, according to Shunsuke Mori, MD, of Kumamoto Saishunsou National Hospital in Kohshi, and Yukitaka Ueki, MD, of Sasebo Chuo Hospital in Nagasaki.
In addition, median flare-free time was 21 months (95% CI 4.1-37.9) following dose reduction, but only 7 months (95% CI 2.8-11.2) after withdrawal, the researchers reported online in Clinical Rheumatology. 

Tofacitinib is an oral small molecule JAK inhibitor that has shown relatively similar efficacy and safety as the biologic disease-modifying antirheumatic drugs, either alone or in combination with methotrexate. Because of the high costs and risks of adverse events with contemporary treatments for rheumatoid arthritis, there is considerable interest in the possibility of treatment tapering for patients who achieve persistent remission. Clinical experience has shown that for some agents, such as tumor necrosis factor inhibitors, tocilizumab (Actemra) and abatacept (Orencia), tapering and even withdrawal can be successful for a subset of patients. Data on this have been lacking for tofacitinib, however.  Accordingly, the researchers prospectively enrolled 100 patients from 2013 to 2017 who had moderate or high scores on the Clinical Disease Activity Index (CDAI). Scores on the CDAI were defined as remission (below 2.8), low disease activity (2.8-10), moderate (10-22), and high (above 22). Patients' mean age was 64, and mean baseline CDAI was 24.5. All patients received tofacitinib, 5 mg twice daily for a full year, at which time the choice of withdrawal, tapering, or continuation was made by the treating physician and patient. Stable doses of methotrexate and/or prednisolone were permitted. Patients who flared were given rescue therapy, which involved restarting tofacitinib at full doses for those in the withdrawal group, returning to full doses for those in the dose-reduction group, and switching to a different agent for those in the continuation group.A total of 68 patients achieved and maintained remission or low disease activity for a median of 49 weeks and were included in the analysis. Because the treatment assignments were not randomized, there were baseline differences between the groups. For instance, disease duration was 3.5 years in the withdrawal group of 19 patients, 7.7 years in the dose-reduction group of 31 patients, and 8 years in the continuation group of 18 patients, and CDAI after 1 year of tofacitinib was 1 in the withdrawal group, 1.5 in the dose reduction group, and 3.8 in the continuation group.Methotrexate also was more often used in the withdrawal and dose-reduction groups, the researchers noted.During a mean follow-up of 12.2 months, 73.7% of patients in the withdrawal group experienced a flare, while during 10.6 months of follow-up, 38.7% of the dose-reduction group flared, and during 17.3 months of follow-up, 5.6% of the continuation group flared.Mean time to flare was 12.5 months (95% CI 7.1-18.4) in the withdrawal group, 15.7 months (95% CI 12.5-18.9) in the dose-reduction group, and 33.3 months (95% CI 30.1-36.5) in the continuation group. At 12 months, the probabilities of flare-free survival in the three groups were 32%, 66%, and 94%, respectively.On a multivariate analysis, the adjusted hazard ratio for disease flare was 18.1 (95% CI 2.38-138, P=0.005) following withdrawal versus continuation and 9.13 (95% CI 1.18-70.4, P=0.03) with dose reduction versus continuation."These findings suggest that, although immediate withdrawal of tofacitinib may be a feasible strategy in rheumatoid arthritis patients who have entered clinical remission or low disease activity, a dose-reduction strategy seems a better option for most patients," observed Mori and Ueki.Among patients who flared, all but one in the withdrawal group regained disease control within a month of restarting tofacitinib, and all of those in the dose-reduction group regained control within a month of returning to the higher dose. One patient in the continuation group who flared switched treatment to abatacept.

The question of whether disease control can be promptly regained following flare is critical, the researchers said, adding that the finding of almost all patients regaining control within 1 month was noteworthy: "Such rapid and remarkable recovery of disease control" should encourage consideration of dose reduction or even withdrawal of tofacitinib in some cases for patients who achieve persistent remission or low disease activity, the investigators stated.A limitation of the study, they said, was the lack of randomization, and larger confirmatory studies are needed.The study was supported by the National Hospital Organization of Japan.The authors reported no financial conflicts.last updated