medwireNews: Findings from a phase 2 proof-of-concept study suggest that abatacept may warrant further investigation as a treatment option for certain subsets of people with immunoglobulin (Ig)G4-related disease.
For the single-arm, open-label study, 10 individuals with active IgG4-related disease were given 24 weeks of treatment with once-weekly abatacept 125 mg. Participants were aged a median of 68 years and 70% were men, with a median of five affected organs. A total of three received concomitant prednisone, which was tapered and discontinued by week 4.
John Stone (Harvard Medical School, Boston, Massachusetts, USA) and co-investigators report that at the 24-week follow-up, 30% of patients achieved complete remission, defined as an IgG4-related disease responder index score of 0 points, no recurrence of disease activity since baseline, and a prednisone dose of 0 mg/day after week 4.
Moreover, six participants had a disease response at week 12 (≥1-point improvement from baseline in IgG4-related disease responder index, no disease flares, and no glucocorticoid use since week 4), and this was sustained until week 24 in five patients. Stone et al note that just one of the participants with a disease response at week 24 was treated with prednisolone earlier in the study.
The researchers then evaluated factors associated with abatacept response, finding that all participants with a disease response at week 12 experienced a reduction in serum IgE concentrations, whereas “there was no consistent pattern” in IgE levels among nonresponders.
In addition, responders had a median decrease in circulating plasmoblast levels of around 50%, whereas nonresponders experienced a median increase of approximately 60%, and there was a “consistent and significant decline” in type 2 T follicular helper cells from baseline in responders versus nonresponders, say Stone and team in The Lancet Rheumatology.
They also note that responders had significantly higher numbers of unswitched memory B cells at baseline than nonresponders, suggesting that nonresponders “might have been on the higher end of the disease severity spectrum.”
A total of four adverse events occurred in the study, including one case of thrombocytopenia that developed after abatacept initiation and resolved after discontinuation, and one case each of myocardial infarction, episcleritis, and nonspecific abdominal pain that were not judged to be related to the study treatment.
Writing in an accompanying commentary, Yu Peng and Wen Zhang, both from the National Clinical Research Center for Dermatologic and Immunologic Diseases in Beijing, China, say that the study “has provided at least two important pieces of information.”
Firstly, they point out that if the results are verified in larger studies, “abatacept could provide the opportunity to discontinue glucocorticoids and avoid their side-effects” in certain patients with IgG4-related disease.
And secondly, the variable response among participants “suggests the presence of heterogeneity in IgG4-related disease,” they say. This points to the potential of “[c]lassifying patients into different subgroups according to the predominant immune mechanisms behind the disease and treating them with corresponding targeted medicine,” the authors suggest.
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Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00359-3
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00390-8