medwireNews: A post-hoc analysis of two phase III trials suggests that rheumatoid arthritis (RA) patients who have a poor initial response to tofacitinib treatment are unlikely to achieve low disease activity (LDA) after 6 months or 1 year of treatment with the Janus kinase inhibitor.
Therefore, “[l]ack of early response may be considered when deciding whether to continue treatment with tofacitinib,” say Edward Keystone (Mount Sinai Hospital, Toronto, Ontario, Canada) and co-investigators.
The team analyzed data from ORAL Start – a comparison of twice daily tofacitinib 5 mg or 10 mg with methotrexate among methotrexate-naïve patients – and ORAL Standard, in which patients with an inadequate response to methotrexate were randomly assigned to receive twice daily tofacitinib 5 mg or 10 mg, adalimumab, or placebo followed by tofacitinib, all in addition to methotrexate.
In ORAL Start, 7.2% of 359 patients given tofacitinib 5 mg and 5.4% of 387 patients in the tofacitinib 10 mg group did not respond to treatment by the 3-month follow-up, defined as failing to achieve an improvement of 6 points or more on the Clinical Disease Activity Index (CDAI) score from baseline.
Of the patients who did not respond to tofacitinib, 3.8% of those in the 5 mg group and 28.6% of those given the 10 mg dose achieved LDA (CDAI≤10 points) at the 6-month follow-up.
The negative predictive value for LDA at month 6 associated with failing to achieve a treatment response at month 3 was 96% for tofacitinib 5 mg and 71% for tofacitinib 10 mg in ORAL Start, report the researchers in Arthritis Care & Research.
Similarly, in ORAL Standard, 18.8% of 191 patients receiving tofacitinib 5 mg and 17.5% of the 194 given tofacitinib 10 mg did not respond to treatment at 3 months. Of these patients, 0% and 2.9%, respectively, achieved LDA at the 6-month follow-up, translating into corresponding negative predictive values of more than 90% for both tofacitinib doses.
Keystone and colleagues observed comparable results when considering initial treatment response at the 1-month follow-up, and when Disease Activity Score at 28 joints based on erythrocyte sedimentation rate was used to define treatment response.
“Across both studies, failure to achieve early improvements in disease activity […] was predictive of low probabilities of achieving LDA and remission at months 6 and 12,” they summarize.
The researchers caution that patient numbers were “relatively low” in some treatment groups, and that data from ORAL Start and ORAL Standard could not be pooled due to differing patient populations and study designs.
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