Background/Purpose: Hidradenitis suppurativa (HS) is a multifactorial auto-inflammatory disorder with a prevalence of 1% in North American and European populations. HS may be associated with various systemic inflammatory conditions including arthritis. Transcriptome analyses of inflammatory pathways and single-cell RNA sequencing of injured skin found upregulation of type I interferon (IFN)-regulated genes (IFN signature). Plasma from healthy donors may contain autoantibodies (Abs) neutralizing type I IFN (alpha and/or omega). In patients with systemic lupus erythematosus (SLE), the presence of these antibodies has been associated with less severe disease. We hypothesize that these Abs provide a potential therapeutic strategy in patients with severe refractory flare-up of HS. Thus, we aim to evaluate the feasibility, safety, and to collect preliminary evidences of efficacy of plasma with neutralizing Abs to type I IFN in patients with severe refractory HS.

Methods: We propose a multicentre prospective phase I-II trial in adult patients with severe refractory flare-up of HS (Hurley stage III). This will be a two-level dose escalation (1 or 2 plasmas) trial combining safety (classic 3+3) and efficacy criteria (Fleming two-stage design), with priority given to safety. The total number of patients enrolled will range from 2 (if more than 1 severe adverse event) to 17 patients. Each patient will receive plasma from healthy donors identified as harboring high titers of neutralizing Abs against IFN. The primary endpoint will combine occurrence of serious adverse events and evidence of IFN alpha neutralization at Day 2 (D2) (˃ 90% neutralization of IFN alpha by the recipient’s plasma). Secondary endpoints will be clinical response (defined as at least a 50% reduction in the abscess and inflammatory nodule count), disease activity score (HS-PGA, IHS4, HiSCR), pain intensity, health-related quality of Life (DLQI) and patient satisfaction (Patient Satisfaction Index and Treatment Satisfaction Questionnaire for Medication). IFN alpha neutralization will also be evaluated at hour 1 (after transfusion) and days 7, 14, 21 and 28. Other type I IFN-associated criteria, including anti-IFN alpha auto-Abs and IFN alpha levels at day 0 (pre-transfusion), hour 1 and days 2, 7 14, 21 and 28 will be part of secondary objectives and IFN signature will be assessed in biopsies of HS skin lesion, before and after transfusion.

Results: Expected results: plasma dose escalation will be based on the safety and the transient neutralization of circulating type I IFN. This neutralization is likely to impact the inflammatory response observed in these patients, as well as the associated lesions and pain.

Conclusion: To our knowledge, this will be the first trial assessing the potential for plasma with high titer neutralizing Abs to type I IFN to treat auto-inflammatory diseases. It may open opportunities for such passive immunotherapy in diseases characterized by interferon signature such as HS and SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-plasma-with-high-titer-neutralizing-autoantibodies-to-type-i-interferons-in-patients-with-severe-refractory-flare-up-of-hidradenitis-suppurativa-as-novel-passive-immunotherapy-approach-trial-p/