Treatment with otilimab, a monoclonal antibody that inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), is well tolerated, despite optimal exposure, and may improve synovitis in patients with active rheumatoid arthritis (RA), according to study results published in Lancet Rheumatology.

Previous studies have reported that GM-CSF can act as a proinflammatory cytokine and has an important role in a broad range of immune-mediated conditions, making it a valuable therapeutic target in patients with RA. The objective of the current mechanistic phase 2a study was to determine the effect of otilimab on the GM-CSF-chemokine (C-C motif) ligand 17 (CCL17) axis and synovitis in patients with RA.

The multicenter, randomized, placebo-controlled study ( Identifier: NCT02799472) included adult patients with RA from across 9 sites in the United States, Poland, and Germany. Participants were randomly assigned to receive either 180 mg of subcutaneous otilimab or placebo. The primary outcome was change over time in 112 biomarkers. Secondary end points included change from baseline in synovitis, osteitis, and erosion assessed by the RA magnetic resonance imaging (MRI) Scoring (RAMRIS) system, RA MRI Quantitative (RAMRIQ) score, and safety evaluation.

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A total of 39 patients with RA who were randomly assigned to receive otilimab (n=28) or placebo (n=11) were included in the final cohort. Weekly subcutaneous injections of otilimab 180 mg or placebo were administered for 5 weeks, then every other week until week 10, followed by a 12-week safety follow-up.

Results showed that mean serum concentrations of the GM-CSF-otilimab complex peaked at week 4 (138.4 ng/L), but reduced from week 6 to 12, with CCL17 concentrations decreasing and then returning to baseline at week 12 (least-squares mean ratios at weeks 2, 4, 6, and 8 were 0.65, 0.68, 0.78, and 0.68, respectively). In the placebo group, no significant changes in CCL17 concentrations were noted. There were also no differences between groups for all other biomarkers.

Results from imaging measures of synovitis showed a reduction from baseline to week 12 in patients who received otilimab. Differences in MRI outcomes were minimal, and a trend for reduced synovitis and osteitis was seen early during active treatment, but not at 12 weeks after the treatment was stopped. The RAMRIS synovitis score showed a least-squares mean change from baseline of -1.3 (SE, 0.6) in the otilimab group and a mean change of 0.8 (SE, 1.2) in the placebo group (P =.11). The RAMRIQ synovitis score showed a least-squares mean change from baseline of -1417.0 µL in the otilimab group and -912.3 µL with placebo (P =.75).

All adverse events were reported to be mild or moderate, and the number of adverse events was similar in the otilimab and placebo groups (39% and 36%, respectively). The most common adverse event was cough (7%) in the active treatment group and pain in extremity (18%) and RA (18%) in the placebo group. There were no serious adverse events or deaths.

The study had several limitations, including the relatively small sample size, imbalanced baseline disease-modifying antirheumatic drug use among treatment groups, and the determination of the RAMRIS synovitis score based on assessment by a single radiologist.

“The findings of this study support the rationale for the further clinical development of otilimab as a treatment option for patients with [RA]. Additionally, the effect of otilimab on CCL17 indicates that CCL17 shows promise as a pharmacodynamic biomarker for otilimab in future studies,” the researchers concluded.

Disclosure: This clinical trial was supported by GlaxoSmithKline. Please see the original reference for a full list of authors’ disclosures.


Genovese MC, Berkowitz M, Conaghan PG, et al. MRI of the joint and evaluation of the granulocyte–macrophage colony-stimulating factor–CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study. Lancet Rheumatol. Published online October 7, 2020. doi:10.1016/s2665-9913(20)30224-1