RA-BEAM trial shows that baricitinib improves RA symptoms, slows joint damage

 

Oral baricitinib, when added to standard rheumatoid arthritis treatment, improved symptoms and slowed the progression of joint damage, compared with both placebo and adalimumab, according to a report published online Feb. 15 in the New England Journal of Medicine.

The JAK inhibitor’s beneficial effects were noted as early as the first week of treatment and persisted throughout 1 year of follow-up in an international manufacturer-sponsored phase III trial (RA-BEAM) involving 1,305 adults with moderate to severe active rheumatoid arthritis (RA). The study participants had not responded to methotrexate and had never been treated with biologics; the majority had previously received at least two conventional synthetic disease-modifying antirheumatic drugs (DMARDs), said Peter C. Taylor, MD, PhD, of the Nuffield Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences and the Kennedy Institute of Rheumatology at the University of Oxford (England), and his associates.

The study participants were randomly assigned in a double-blind fashion to receive 4 mg of oral baricitinib once per day (487 patients), 40 mg of subcutaneous adalimumab every other week (330 patients), or matching placebo (488 patients), and were followed at 281 medical centers in 26 countries. Nearly all were also receiving background therapy with methotrexate, plus stable doses of conventional synthetic DMARDs, NSAIDs, analgesics, or glucocorticoids (10 mg or less of prednisone or the equivalent per day) at the discretion of their treating physicians.

The primary efficacy endpoint – the proportion of patients at week 12 who showed a response of 20% or more according to American College of Rheumatology criteria (ACR20) – was 70% for baricitinib, compared with 40% for placebo. Baricitinib also was superior to placebo regarding all the major secondary efficacy endpoints of the study, including scores on the Health Assessment Questionnaire–Disability Index; results on the Disease Activity Score for 28 joints using high-sensitivity C-reactive protein (DAS28-CRP); remission according to the Simplified Disease Activity Index criteria; and the patients’ daily diary reports on duration and severity of morning joint stiffness, worst level of tiredness, and worst level of pain.

In addition, baricitinib was “considered to be significantly superior to adalimumab” according to the ACR20 (61% for adalimumab) and the DAS28-CRP responses at week 12. Both baricitinib and adalimumab were associated with significant reductions in the radiographic progression of structural joint damage, compared with placebo, at week 24 and week 52, the investigators reported (N Engl J Med. 2017;376:652-62).

Regarding safety outcomes, adverse events including infections were more frequent with baricitinib and adalimumab than with placebo, as were decreases in neutrophil counts, increases in aminotransferase and creatinine levels, and increases in low-density lipoprotein cholesterol levels. At 1 year, three patients in the baricitinib group and two in the adalimumab group discontinued treatment because of liver abnormalities.

Baricitinib is currently under consideration for approval by the U.S. Food and Drug Administration and was approved for marketing in the European Union on Feb. 13.

The RA-BEAM trial was supported by Eli Lilly and Incyte. Dr. Taylor reported receiving personal fees from Eli Lilly, and he and his associates reported ties to numerous other industry sources.

 

Oral baricitinib, when added to standard rheumatoid arthritis treatment, improved symptoms and slowed the progression of joint damage, compared with both placebo and adalimumab, according to a report published online Feb. 15 in the New England Journal of Medicine.

The JAK inhibitor’s beneficial effects were noted as early as the first week of treatment and persisted throughout 1 year of follow-up in an international manufacturer-sponsored phase III trial (RA-BEAM) involving 1,305 adults with moderate to severe active rheumatoid arthritis (RA). The study participants had not responded to methotrexate and had never been treated with biologics; the majority had previously received at least two conventional synthetic disease-modifying antirheumatic drugs (DMARDs), said Peter C. Taylor, MD, PhD, of the Nuffield Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences and the Kennedy Institute of Rheumatology at the University of Oxford (England), and his associates.

The study participants were randomly assigned in a double-blind fashion to receive 4 mg of oral baricitinib once per day (487 patients), 40 mg of subcutaneous adalimumab every other week (330 patients), or matching placebo (488 patients), and were followed at 281 medical centers in 26 countries. Nearly all were also receiving background therapy with methotrexate, plus stable doses of conventional synthetic DMARDs, NSAIDs, analgesics, or glucocorticoids (10 mg or less of prednisone or the equivalent per day) at the discretion of their treating physicians.

The primary efficacy endpoint – the proportion of patients at week 12 who showed a response of 20% or more according to American College of Rheumatology criteria (ACR20) – was 70% for baricitinib, compared with 40% for placebo. Baricitinib also was superior to placebo regarding all the major secondary efficacy endpoints of the study, including scores on the Health Assessment Questionnaire–Disability Index; results on the Disease Activity Score for 28 joints using high-sensitivity C-reactive protein (DAS28-CRP); remission according to the Simplified Disease Activity Index criteria; and the patients’ daily diary reports on duration and severity of morning joint stiffness, worst level of tiredness, and worst level of pain.

In addition, baricitinib was “considered to be significantly superior to adalimumab” according to the ACR20 (61% for adalimumab) and the DAS28-CRP responses at week 12. Both baricitinib and adalimumab were associated with significant reductions in the radiographic progression of structural joint damage, compared with placebo, at week 24 and week 52, the investigators reported (N Engl J Med. 2017;376:652-62).

Regarding safety outcomes, adverse events including infections were more frequent with baricitinib and adalimumab than with placebo, as were decreases in neutrophil counts, increases in aminotransferase and creatinine levels, and increases in low-density lipoprotein cholesterol levels. At 1 year, three patients in the baricitinib group and two in the adalimumab group discontinued treatment because of liver abnormalities.

Baricitinib is currently under consideration for approval by the U.S. Food and Drug Administration and was approved for marketing in the European Union on Feb. 13.

The RA-BEAM trial was supported by Eli Lilly and Incyte. Dr. Taylor reported receiving personal fees from Eli Lilly, and he and his associates reported ties to numerous other industry sources.

 

Oral baricitinib, when added to standard rheumatoid arthritis treatment, improved symptoms and slowed the progression of joint damage, compared with both placebo and adalimumab, according to a report published online Feb. 15 in the New England Journal of Medicine.

The JAK inhibitor’s beneficial effects were noted as early as the first week of treatment and persisted throughout 1 year of follow-up in an international manufacturer-sponsored phase III trial (RA-BEAM) involving 1,305 adults with moderate to severe active rheumatoid arthritis (RA). The study participants had not responded to methotrexate and had never been treated with biologics; the majority had previously received at least two conventional synthetic disease-modifying antirheumatic drugs (DMARDs), said Peter C. Taylor, MD, PhD, of the Nuffield Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences and the Kennedy Institute of Rheumatology at the University of Oxford (England), and his associates.

The study participants were randomly assigned in a double-blind fashion to receive 4 mg of oral baricitinib once per day (487 patients), 40 mg of subcutaneous adalimumab every other week (330 patients), or matching placebo (488 patients), and were followed at 281 medical centers in 26 countries. Nearly all were also receiving background therapy with methotrexate, plus stable doses of conventional synthetic DMARDs, NSAIDs, analgesics, or glucocorticoids (10 mg or less of prednisone or the equivalent per day) at the discretion of their treating physicians.

The primary efficacy endpoint – the proportion of patients at week 12 who showed a response of 20% or more according to American College of Rheumatology criteria (ACR20) – was 70% for baricitinib, compared with 40% for placebo. Baricitinib also was superior to placebo regarding all the major secondary efficacy endpoints of the study, including scores on the Health Assessment Questionnaire–Disability Index; results on the Disease Activity Score for 28 joints using high-sensitivity C-reactive protein (DAS28-CRP); remission according to the Simplified Disease Activity Index criteria; and the patients’ daily diary reports on duration and severity of morning joint stiffness, worst level of tiredness, and worst level of pain.

In addition, baricitinib was “considered to be significantly superior to adalimumab” according to the ACR20 (61% for adalimumab) and the DAS28-CRP responses at week 12. Both baricitinib and adalimumab were associated with significant reductions in the radiographic progression of structural joint damage, compared with placebo, at week 24 and week 52, the investigators reported (N Engl J Med. 2017;376:652-62).

Regarding safety outcomes, adverse events including infections were more frequent with baricitinib and adalimumab than with placebo, as were decreases in neutrophil counts, increases in aminotransferase and creatinine levels, and increases in low-density lipoprotein cholesterol levels. At 1 year, three patients in the baricitinib group and two in the adalimumab group discontinued treatment because of liver abnormalities.

Baricitinib is currently under consideration for approval by the U.S. Food and Drug Administration and was approved for marketing in the European Union on Feb. 13.

The RA-BEAM trial was supported by Eli Lilly and Incyte. Dr. Taylor reported receiving personal fees from Eli Lilly, and he and his associates reported ties to numerous other industry sources.