Antibody-Drug Conjugate Tackles Glucocorticoid Use in PMR

TOPLINE:

ABBV-154, an antibody-drug conjugate comprising adalimumab conjugated to a proprietary glucocorticoid receptor modulator, shows potential for extending flare-free periods in patients with glucocorticoid-dependent polymyalgia rheumatica (PMR), with the ability to reduce glucocorticoid dose.

METHODOLOGY:

• In a phase 2 randomized controlled trial conducted across 70 centers in multiple countries, researchers evaluated the efficacy and safety of a novel antibody-drug conjugate, ABBV-154, in 181 patients (mean age, 69.4 years; 64.6% women; 87.8% White) with glucocorticoid-dependent PMR who experienced at least two PMR flares while glucocorticoids were being tapered.
• Patients were randomly assigned to receive either a placebo (n = 50) or ABBV-154 at doses of 40 mg (n = 42), 150 mg (n = 45), or 340 mg (n = 44); both treatments were administered subcutaneously once every other week alongside a standardized glucocorticoid tapering regimen.
• The primary endpoint was the time to flare, defined as clinical signs and symptoms of PMR and the need to increase the glucocorticoid dose; the secondary endpoints were achievement of a flare-free state, cumulative glucocorticoid dose, and changes in glucocorticoid dose by week 24.
• The study was terminated early before the planned primary analysis of data because an interim review indicated that ABBV-154 did not demonstrate a benefit-risk profile sufficiently differentiated from that of existing therapies.

TAKEAWAY:

• Compared with placebo, ABBV-154 extended the time to flare, with a significant reduction in flare risk (hazard ratio [HR], 0.49; P = .017 for 40 mg; HR, 0.44; P = .006 for 150 mg; and HR, 0.20; P 
• A higher proportion of patients receiving ABBV-154 (340 mg) achieved a flare-free state by week 24 than those on placebo (70.6% vs 28.2%; P P = .002).
• Patients receiving ABBV-154 had a lower cumulative glucocorticoid dose by week 24 than those on placebo (mean difference, −164.8 mg for 150 mg; P = .007 and −182.6 mg for 340 mg; P = .003).
• The incidence of treatment-emergent adverse events was similar across groups, with COVID-19, nasopharyngitis, and arthralgia being the most common events. Two malignancies (one event each) were considered to be possibly related to the ABBV-154 treatment.

IN PRACTICE:

“Given the limited sample size and duration of exposure to study drug, no definite conclusions can be drawn from this study of ABBV-154 in patients with PMR, and caution should be exercised when interpreting the results,” the authors wrote. “Nevertheless, this study supports that a GRM [glucocorticoid receptor modulator] payload targeted to transmembrane TNF [tumor necrosis factor]–expressing cells, including activated immune cells, could be beneficial in PMR.”

SOURCE:

The study was led by Robert F. Spiera, MD, Hospital for Special Surgery, Weill Medical College of Cornell University, New York City. It was published online on January 27, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

The early termination of the study limited the sample size and duration of exposure to ABBV-154, affecting the robustness of the findings. The absence of an adalimumab comparator arm limited direct comparisons and the ability to fully assess the contribution of the glucocorticoid receptor modulator payload. Additionally, the PMR activity score was not a primary or secondary endpoint, restricting comparisons with other studies.

DISCLOSURES:

This study was funded by AbbVie, which participated in the study design, research, data collection, analysis, interpretation of data, reviewing, and approval of this manuscript. Some authors reported having financial relationships with pharmaceutical companies, including AbbVie.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.