EULAR and ACR guidelines for the management of polymyalgia rheumatica (PMR) recommend treatment with oral glucocorticoids (i.e., prednisone or equivalent) for the shortest effective duration, with individualized dose-tapering after remission. However, glucocorticoid reduction can lead to PMR disease flare, resulting in continued, long-term, glucocorticoid use and potential glucocorticoid-associated morbidity. Thus, an unmet need exists for glucocorticoid-sparing treatments for patients with PMR.
In a phase 2 study, Spiera et al. investigated the use of ABBV-154, a novel antibody-drug conjugate comprising adalimumab conjugated to a glucocorticoid receptor modulator, for the treatment of patients with PMR. This agent targets cells expressing transmembrane tumor necrosis factor, including activated immune cells.
The randomized, double-blind study evaluated the efficacy and safety of three different doses of ABBV-154 vs. placebo in patients with glucocorticoid-dependent PMR.
Methods
For the study, patients (N=181) had confirmed PMR and glucocorticoid response, as well as two or more PMR flares while tapering glucocorticoids. Study patients were also taking 5 mg or more of daily prednisone or an equivalent.
In the study, patients were randomized to receive either subcutaneous placebo (n=50), 40 mg of ABBV-154 (n=42), 150 mg of ABBV-154 (n=45) or 340 mg of ABBV-154 (n=44) once every other week. The study’s primary efficacy end point was time to flare.
(Note: The study’s sponsor, AbbVie, voluntarily terminated the study at week 24.)
The Results
In the treatment groups, 67.4% of patients completed the study at week 24. A treatment effect was observed in all three treatment groups, with patients who received ABBV-154 experiencing a longer time to flare than those receiving placebo. Based on the Kaplan-Meier estimate, patients in the placebo group had a lower 24-week, flare-free rate.
The hazard ratios of ABBV-154 vs. placebo were:
- 40 mg of ABBV-154 group: 0.49 (95% confidence interval [CI]; 0.27–0.88), P=0.017);
- 150 mg of ABBV-154 group: 0.44 (95% CI; 0.25–0.79), P=0.006; and
- 340 mg of ABBV-154 group: 0.20 (95% CI; 0.09–0.42), P<0.001.
At week 24, a higher proportion of patients receiving ABBV-154 vs. placebo achieved a flare-free state, had a lower cumulative dose of glucocorticoids and had a greater reduction from baseline of daily glucocorticoid dose. Also, a higher proportion of patients receiving ABBV-154 showed improvement in markers of inflammation by week 24 than those receiving placebo.
Incidents of treatment emergent adverse events were similar between groups, with the most common across ABBV-154 cohorts being COVID-19 (16%).
Overall, ABBV-154 was generally well tolerated with benefits observed vs. placebo. The study authors note that, due to early study termination, results should be interpreted with caution.
For complete details, including source material, refer to the full study.
Excerpted and adapted from:
Spiera RF, Devauchelle-Pensec V, Owen CE, et al. Efficacy, safety, pharmacokinetics and immunogenicity of ABBV-154 in adults with glucocorticoid-dependent polymyalgia rheumatica: A phase 2, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2025 Aug;77(8):1041–1051.
