HealthDay News — Adding tofacitinib (Xeljanz) to rheumatoid arthritis treatment regimens helps ease symptoms in patients who don’t respond to conventional disease-modifying anti-rheumatic drugs (DMARDs),findings from the ORAL Sync trial show.

Tofacitinib increased the proportion of patients who experienced at least a 20% improvement in their disease as measured by American College of Rheumatology criteria (ACR20) from 21% to 26% over placebo when added to nonbiologic treatments (P<0.001), Joel Kremer, MD, of New York’s Albany Medical College, and colleagues reported in Annals of Internal Medicine.

It also lessened arthritis-related disability and swollen joint counts, they found.

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The oral Janus kinase inhibitor was approved for rheumatoid arthritis treatment in late 2012, though with a boxed warning about risks of serious infections, lymphoma and other malignancies. In this trial there were two cases of tuberculosis, two cases of other opportunistic infections (disseminated herpes zoster and cryptococcal pneumonia), three cardiovascular events and four deaths (one deemed treatment-related).

Additionally, in the tofacitinib groups, neutrophil counts decreased, hemoglobin and low- and high-density lipoprotein cholesterol levels increased, and serum creatinine levels had small increases.

The study involved 792 patients with active RA despite treatment with nonbiologic DMARD therapy from 114 centers in 19 countries. Most of the patients (79%) were on methotrexate as a background DMARD. One quarter to one third of patients remained on two or more background DMARDs through the study.

Patients were randomly assigned to 5 mg or 10 mg tofacitinib twice daily or placebo, advanced to active drug at month 6 (or earlier if no response at month 3).

Improvement was determined using ACR20 criteria; Disease Activity Score for 28-joint counts (DAS28-4) based on an erythrocyte sedimentation rate (ESR) of less than 2.6; DAS28-4 ESR-defined remission; and change in Health Assessment Questionnaire Disability Index (HAQ-DI) score.

The ACR20 response rate at month 6 of the 12 month trial was 56.5% with 10 mg tofacitinib and 52.1% with 5 mg tofacitinib, both significant at P<0.001 compared with the placebo rate of 30.8%.

DAS28-4 ESR counts came in under 2.6, for 12.5% of patients on the higher tofacitinib dose, 8.5% on the lower dose, and 2.6% with placebo at month six, all of which were significant.

For the third primary endpoint, the HAQ-DI score improved by 0.53 points at month three with the 10 mg tofacitinib dose and 0.44 points with the 5 mg dose, both exceeding the 0.22 threshold for a minimum clinically important difference and significantly more than the 0.16 improvement in the placebo group (both P<0.001).

For patients receiving 5-mg tofacitinib, 10-mg tofacitinib and placebo, the incidence rates of serious adverse events were 6.9, 7.3, and 10.9 events per 100 patient-years of exposure, respectively.


  1. Kremer J et al. Ann Intern Med. 2013;159(4):253-261.