Patients with rheumatoid arthritis who received 3 months of treatment with the investigational Janus kinase inhibitor tofacitinib had clinically significant improvements in patient-reported outcomes, compared with those who were given placebo, according to Dr. Vibeke Strand, who reported the 3-month results of a 6-month, phase III trial on May 26.
"I see this drug as being everything that a biologic is. ...There are a lot of places where biologics are not very accessible. ... The data look quite comparable to biologics," Dr. Strand said in an interview.
Dr. Vibeke Strand
The study marks the first of five pivotal, phase III, randomized, placebo-controlled trials planned for tofacitinib (CP-690-550), Dr. Strand said in an interview. She described tofacitinib as "the first of several Janus kinase and Syk kinase inhibitors that are promising oral disease-modifying antirheumatic drugs with onset of effect that is rapid and magnitude of effect similar to anti–[tumor necrosis factor] therapies," said Dr. Strand of the division of immunology/rheumatology at Stanford (Calif.) University. Tofacitinib "has been studied vs. monotherapy adalimumab in phase II."
For the current 6-month trial, 610 rheumatoid arthritis (RA) patients were randomized to one of three treatments: tofacitinib 5 mg b.i.d., tofacitinib 10 mg b.i.d., or placebo, all as monotherapy. Patients on placebo were advanced to either tofacitinib 5 mg b.i.d. or tofacitinib 10 mg b.i.d. after month 3. The mean age of the patients was 51 years, and 87% were women.
In her presentation, Dr. Strand reported change-from-baseline results on several patient-reported outcomes at 3 months, including Patient Global Assessment of disease activity on a visual analog scale, pain on a visual analog scale, physical function by the HAQ-DI (Health Assessment Questionnaire–Disability Index), and health-related quality of life by the MOS SF-36 (Medical Outcomes Study 36-item Short Form Health Survey).
Improvements were reported as least square means of changes from baseline. At 3 months, treatment with tofacitinib monotherapy resulted in statistically significant and clinically meaningful improvements, compared with placebo, in all patient-reported outcomes except sleep improvement in the tofacitinib 5-mg group.
Mean Patient Global Assessment scores achieved a minimally clinically important difference (MCID) relative to baseline in 73% of the patients taking 5 mg (number needed to treat, 4), in 75% of patients taking10 mg (NNT, 3.8), and in 48% of the placebo group.
Patients’ pain scores showed an MCID relative to baseline in 70% of the patients on 5 mg (NNT, 4.6), in 77% of the patients on 10 mg (NNT, 3.5), and in 48% of the patients on placebo.
Physical function scores on the HAQ-DI showed an MCID relative to baseline in 61% of the patients on 5 mg (NNT, 5.7), in 68% in patients taking 10 mg (NNT, 4), and in 43% of those on placebo.
The physical component scores on the MOS SF-36 were 2.63, 6.97, and 8.55, respectively. Physical component scores on the MOS SF-36 showed an MCID relative to baseline in 68% of the patients on 5 mg (NNT, 4.2), in 75% of the group on 10 mg (NNT, 3.2), and in 44% of those on placebo.
"Randomized, controlled trial data don’t always reflect what we see in the clinic, but this product has a large phase II database, and these findings are consistent with those data," Dr. Strand said. "Patients clearly have derived early and clinically meaningful benefit from treatment – in pain, fatigue, physical function, and ‘multidimensional function’ [as shown] in the SF-36 – which reflects improvements in those parameters, and not just physical and emotional well-being but also in social functioning and mental health."
Dr. Strand disclosed that she is a paid consultant to Pfizer but said that she received no support for preparation of the abstract or presentation.