Baricitinib shows encouraging phase III results in RA

SAN FRANCISCO – Baricitinib, an investigational oral investigational JAK 1/2 inhibitor, was significantly superior to adalimumab and to placebo in the treatment of patients with active rheumatoid arthritis despite background methotrexate in the phase III RA-BEAM study.

Patients taking baricitinib had significant improvements in signs and symptoms of rheumatoid arthritis (RA), physical function, and patient-reported outcomes. These encouraging results, reported at a late-breaking abstract session during the annual meeting of the American College of Rheumatology, come on the heels of other positive phase III studies of this drug in treatment-naive patients and those with an inadequate response to anti-TNF agents plus methotrexate.

“I feel that this is a real clinical benefit we see with baricitinib, but we will need further studies. The safety and tolerability of baricitinib are satisfactory and consistent with other phase II and III studies reported at this meeting,” said Dr. Peter Taylor of the Kennedy Institute of Rheumatology at University of Oxford (England).

Dr. Peter Taylor

“The most important finding is that baricitinib administered with methotrexate is a superior treatment to methotrexate alone, but another interesting finding is that the baricitinib/methotrexate combination was superior to adalimumab [Humira] plus methotrexate,” Dr. Taylor added.

“Baricitinib is an oral, highly selective inhibitor of JAK 2, and the drug improves disease activity with acceptable safety in patients with an inadequate response to conventional therapy and also in disease-modifying antirheumatic drug [DMARD]-naive patients with rheumatoid arthritis,” Dr. Taylor told the audience.

The RA-BEAM study enrolled 1,307 RA patients who had an inadequate response to methotrexate. Patients were randomized 3:3:2 to placebo, baricitinib 4 mg/day or adalimumab 40 mg biweekly. From week 16 on, nonresponders were rescued with 4 mg baricitinib. All patients continued on stable doses of background methotrexate.

Median age of the patients was 50 years, and a majority were seropositive for rheumatoid factor. The mean methotrexate dose was 15 mg/once weekly, and 60% of patients were taking concomitant oral glucocorticoids.

At baseline, groups were well balanced for disease activity, disease duration, and demographic characteristics. The mean number of swollen joints was 16 and mean number of tender joints 23.

“These patients had marked disability and high baseline disease activity,” Dr. Taylor said.

At week 24, about 84%-90% of patients remained on study, and at week 52, more than 80% were still on study.

Rescue rates were 26% for placebo patients, 7% for baricitinib-treated patients, and 12% for those randomized to adalimumab.

For the primary endpoint of at least a 20% response at 12 weeks according to ACR criteria (i.e., ACR20), baricitinib was superior to both adalimumab and placebo (plus methotrexate in all three arms). ACR20 was achieved in 40% of patients in the placebo arm, 61% of those in the adalimumab arm, and by 70% of those taking baricitinib (P less than .001 for both comparisons versus placebo).

At week 24, the same pattern was observed for ACR20, ACR50, and ACR70. An ACR20 response was achieved by 37% with placebo, 66% with adalimumab, and 74% with baricitinib. For ACR50, response rates were 19%, 46%, and 50%, respectively. For ACR70, response rates were 9%, 22%, and 30%, respectively. (The P value was less than .001 for all comparisons versus placebo.)

Significantly more patients in the baricitinib-plus-methotrexate arm achieved low disease activity or remission, compared with placebo and with adalimumab plus methotrexate. Over time, the benefits increased in the baricitinib arm.

“A rapid reduction was observed in the number of swollen joints and tender joints with baricitinib and adalimumab, but the reduction was deeper with baricitinib,” said Dr. Taylor. “Patient-reported outcomes, such as joint stiffness and pain and fatigue, were improved on baricitinib as early as week 1, compared with placebo.

Both baricitinib and adalimumab achieved a greater inhibition on structural damage, compared with placebo, and this difference was maintained at week 52.

The percentage of patients with no change in Sharp van der Heijde Score was 70% for placebo, 79% for baricitinib, and 81% for adalimumab.

Rates of treatment-emergent adverse events were higher for the active treatment groups versus placebo: during weeks 0-12, 47.3% for placebo, 52.8% for baricitinib, and 50.9% for adalimumab. Infection rates during weeks 0-12 were 17.8%, 21.8%, and 20%, respectively.

The rates of serious adverse events during weeks 0-12 were 2.7% for placebo, 2.3% for baricitinib, and 1.2% for adalimumab, respectively. During an additional 12 weeks they rose further to 4.3%, 4.5%, and 1.8%, respectively.

There were four cases of malignancy reported in the baricitinib group and none in the adalimumab group in weeks 0-24. Two deaths were reported in the baricitinib group and none in the other two groups.