In patients with rheumatoid arthritis (RA) who are methotrexate-inadequate responders (MTX-IR), lack of early response to tofacitinib is predictive of a low probability of achieving low disease activity (LDA) at 6 months, according to the results of 2 randomized double-blind phase 3 studies published in Arthritis Care & Research.
The investigators of this post-hoc analysis of the two studies (ORAL Start ClinicalTrials.gov identifier: NCT01039688 and ORAL Standard ClinicalTrials.gov identifier: NCT00853385) sought to examine the link between early disease activity changes and the attainment of LDA and remission targets in tofacitinib-treated patients with RA.
In the ORAL Start study, MTX-naive patients with RA received tofacitinib 5 or 10 mg twice daily (BID), or MTX, for 24 months. In the placebo-controlled ORAL Standard study, MTX-IR patients with RA were treated with tofacitinib 5 or 10 mg BID or adalimumab 40 mg once every 2 weeks with methotrexate for 12 months.
The probability of achieving LDA (defined as Clinical Disease Activity Index [CDAI] ≤10 or Disease Activity Score [28 joints, 4 components [DAS28-4] erythrocyte sedimentation rate [ESR] ≤3.2) at 6 and 12 months were computed, given failure to attain threshold improvement from baseline (ie, change in CDAI ≥6 and change in DAS28-4[ESR] ≥1.2) at 1 or 3 months.
In the ORAL Start study, 7.2% and 5.4% of patients treated with tofacitinib 5 mg BID and tofacitinib 10 mg BID, respectively, did not achieve improvements in CDAI ≥6 at 3 months. In patients who did not respond to treatment, 3.8% and 28.6%, respectively, attained CDAI-defined LDA at 6 months. In the ORAL Standard study, 18.8% and 17.5% of patients treated with tofacitinib 5 mg BID and tofacitinib 10 mg BID, respectively, did not achieve improvements in CDAI ≥6 at 3 months.
In patients who did not respond to treatment, 0% and 2.9%, respectively, attained CDAI-defined LDA at 6 months. Similar findings were reported with respect to improvements in DAS28-4(ESR) thresholds at 1 month.
The investigators concluded that when clinicians are deciding whether or not to continue tofacitinib therapy in their patients with moderately to severely active RA, lack of early response must be taken into account. Lack of improvements in disease activity at 1 and 3 months predicts a low probability of attaining LDA and remission at 6 and 12 months.
Van Vollenhoven RF, Lee EB, Fallon L, et al. Tofacitinib in rheumatoid arthritis: lack of early change in disease activity predicts a low probability of achieving low disease activity at month 6 [published online April 26, 2018]. Arthritis Care Res (Hoboken). doi:10.1002/acr.23585