Baricitinib keeps radiographic progression levels low in rheumatoid arthritis

Treatment with oral baricitinib steadily inhibits radiographic progression of structural joint damage in most patients with rheumatoid arthritis (RA), while achieving clinical improvement in disease activity, through 5 years as compared with initial conventional synthetic disease-modifying antirheumatic drug (csDMARD) or placebo, results of a study have shown.

“Patients initially treated with baricitinib had less radiographic progression over the duration of the trial compared to those initially treated with a csDMARD plus placebo or methotrexate (MTX) monotherapy (DMARD-naïve patients),” the researchers said.

Patients completed one of three phase III baricitinib trials (ie, NCT01711359, NCT01710358, or NCT01721057) and entered the long-term extension RA-BEYOND (NCT01885078), in which they received baricitinib 2 or 4 mg once daily.

Across trials, patients initially prescribed MTX or adalimumab (ADA) switched to baricitinib 4 mg at week 52, while those initially on placebo switched to baricitinib 4 mg at week 24. The researchers then scored radiographs at baseline and years 2, 3, 4, and 5. They also calculated changes in van der Heijde modified total Sharp score (ΔmTSS) from baseline.

Of the 2,573 patients randomized in the trials, 2,125 (82.6 percent) entered RA-BEYOND; 1,837 of 2,125 (86.4 percent) then entered the current analysis. [J Rheumatol 2022;49:133-141]

From years 3 to 5, significantly more DMARD-naïve patients on initial baricitinib monotherapy or with MTX showed no progression than those on initial MTX (ΔmTSS ≤0 at year 5: 59.6 percent with baricitinib 4 mg and 66.2 percent with baricitinib 4 mg plus MTX vs 40.7 percent with MTX).

More patients with inadequate response (IR) to MTX on initial baricitinib or ADA also had no progression relative to those on placebo (ΔmTSS ≤0 at year 5: 54.8 percent with baricitinib 4 mg and 55.0 percent with ADA vs 50.3 percent with placebo).

Likewise, a higher number of patients with csDMARD-IR on initial baricitinib 4 mg maintained less progression than those initially on placebo or baricitinib 2 mg (ΔmTSS ≤0 at year 5: 66.7 percent with baricitinib 4 mg and 58.2 percent with baricitinib 2 mg vs 60.0 percent with placebo).

Early treatment

“The key result of this analysis is that approximately 40–72 percent of patients, depending on their originating study and dose of baricitinib, treated with baricitinib 2 or 4 mg combined with a csDMARD (or 4 mg monotherapy for DMARD-naïve patients), had no radiographic progression (threshold of mTSS ≤0) over 5 years,” the researchers said.

In addition, most patients kept a low disease activity (LDA), as defined by the Simplified Disease Activity Index (SDAI) score. This observation was consistent with a previous report on RA-BEYOND of SDAI LDA data from patients originally treated with or switched to baricitinib. [RMD Open 2019;5:e000898; Rheumatology 2021;60;2256-2266]

The findings suggest “that one should start a medication such as baricitinib earlier in the disease course if patients have not reached remission, according to American College of Rheumatology/European Alliance of Associations for Rheumatology criteria or at least LDA with a metric such as the SDAI or Clinical Disease Activity Index, within 3–6 months as suggested by the treat-to-target strategy,” the researchers said. [Ann Rheum Dis 2016;75:3-15]