Tofacitinib Reinitiation Safe, Efficacious Following Treatment Interruption

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It is possible to re-establish the effect of tofacitinib therapy following temporary withdrawal and reinitiation, according to research published in Clinical Rheumatology.

It is possible to re-establish the effect of tofacitinib therapy following temporary withdrawal and reinitiation, according to research published in Clinical Rheumatology. This reinitiation yields a safety profile consistent with that of uninterrupted treatment.

Using data from the ORAL Sequel trial ( identifier NCT00413699), a global, multicenter, open-label, long-term extension study. Researchers sought to assess the safety and efficacy of tofacitinib therapy in patients with rheumatoid arthritis during and after 2 full weeks of temporary discontinuation and subsequent reinitiation.

Patients in the sub-study were randomly assigned 1:1 to receive either continuous or interrupted tofacitinib treatment, stratified by current background methotrexate use. Those receiving continuous treatment included patients who received tofacitinib 10 mg twice daily as either monotherapy or in combination with methotrexate. Those receiving interrupted treatment were treated with tofacitinib 10 mg twice daily, which was withdrawn for 2 weeks post-randomization. Reinitiation was undertaken as either monotherapy or in combination with methotrexate at day 15.

In total, 199 patients were included in the sub-study of which 100 received continuous treatment and 99 received interrupted treatment. Both groups were similar in terms of age, sex, race, and various other baseline variables.

Of the 100 patients who were randomly assigned to a treatment group, 99 received continuous tofacitinib, and 58.6% received concomitant methotrexate (mean 14.1±4.1 mg/week). Among the patients in the interrupted treatment group, all received tofacitinib, and 59.6% received concomitant methotrexate (mean 15.9±3.9 mg/week).

Compared with interrupted treatment group, there was a significantly higher proportion of patients who received an American College of Rheumatology 20% response (ACR20) in the continuous treatment group (67.7%; 95% CI, 57.5-76.7 vs 80.8%; 95% CI, 71.7-88.0; difference, 13.1%). Between the 2 groups, the difference increased to 28.8% by day 8 (95% CI, 16.0-41.5). Investigators noted that the ACR20 response rate remained fairly consistent for patients who received continuous treatment but decreased with interrupted treatment (81.4% vs 52.7%). By day 43 — 28 days post-treatment reinitiation — ACR20 response rate among the interrupted treatment group increased to 72.6% (95% CI, 62.5-81.3).

ACR50 response rates were similar between the continuous and interrupted treatment groups at sub-study baseline (51.5% vs 46.5%, respectively; difference, 5.1%). Response rates remained similar across the continuous treatment group at days 8, 15, and 43 (55.7%, 54.1%, and 54.6% respectively). In the interrupted treatment group, responses decreased slightly. However, the ACR50 response rates in the interrupted treatment group decreased slightly and were significantly different from the continuous treatment group at days 8 and 15 (38.7% and 37.1%, respectively). By day 43, the ACR50 response rate for the interrupted treatment group had climbed to 46.3% and was not significantly different from the continuous treatment group. ACR70 response rates also remained consistent in the continuous treatment group, with response rates that were numerically lower but not significantly different in the interrupted treatment group.

The interrupted treatment group also experienced significantly greater increases from baseline in C-reactive protein levels, Health Assessment Questionnaire-Disability Index, Disease Activity Score in 28 Joints-Erythrocyte Sedimentation Rate, and Clinical Disease Activity Index. By day 43, however, changes from baseline were similar to sub-study baseline levels, and investigators noted little change compared with the continuous treatment group.

In terms of safety, a greater number of treatment-emergent adverse events were reported in the interrupted treatment group, with bronchitis, upper respiratory tract infections, vaccination-related immunization reactions, myalgia, and rash being the most common. Three patients in each treatment group experienced serious adverse events.

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Study limitations included the small sample size, the relatively short follow-up period after treatment reinitiation, and examination of a dose different than the approved treatment dose in most countries.

“The results of this analysis showed that disease outcomes worsened during the temporary discontinuation of tofacitinib, and that [tofacitinib efficacy] can be re-established after the temporary withdrawal and reinitiation of the drug,” the researchers concluded.

Disclosure: This clinical trial was supported by Pfizer, Inc. Please see the original reference for a full list of authors’ disclosures.


Kaine J, Tesser J, Takiya L, et al. Re-establishment of efficacy of tofacitinib, an oral JAK inhibitor, after temporary discontinuation in patients with rheumatoid arthritis [published online February 12, 2020]. Clin Rheumatol. doi: 10.1007/s10067-020-04956-1