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%).
