Targeting B cells, plasma cells may aid hidradenitis suppurativa treatment

Key takeaways:

• Significant nodule and abscess decreases were observed in most patients with hidradenitis suppurativa treated with fostamatinib.
• Adverse events were mild and did not lead to discontinuation.

Patients with hidradenitis suppurativa saw improvement with fostamatinib treatment, showing that targeting B cells and plasma cells could be an upcoming strategy in treating the disease, according to a study.

“The pathogenesis of HS is associated with activation of the Th17 immune axis as witness in the success of Th17 antagonists in HS; however, there is a strong presence of multiple other cell types including B cells and plasma cells, which are known to be present and immunologically active in HS,” Rebecca Jepsen, RN, of Holdsworth House Medical Practice and the laboratory of translational cutaneous medicine at Ingham Institute for Applied Medical Research, both in Sydney, and colleagues wrote. “Fostamatinib is a spleen tyrosine kinase (SYK) antagonist which reversibly inhibits the production of immunoglobulins by plasma cells, and the migration and activation of B cells.”

Researchers conducted an open-label, phase 2, proof-of-concept study to evaluate fostamatinib’s safety, tolerability and efficacy in 20 patients with HS aged 18 years and older.

Each subject received 100 mg of oral fostamatinib twice daily for 4 weeks and escalated to 150 mg twice daily from weeks 5 through 12. Any patients who had an adverse drug-related event had their dose decreased to 100 mg.

All patients completed 12 weeks of treatment and 18 patients completed the trial including tissue biopsies and serum collection.

Adverse events during the trial were all deemed to be mild, with nausea, hypertension, transaminitis and diarrhea being the most common. The two patients who experienced hypertension had pre-existing hypertension history controlled with medication and both reduced the fostamatinib dose to 100 mg, which resolved their hypertension.

Two patients withdrew from the trial at week 12 due to severe disease flare.

Within the first week of fostamatinib treatment a significant reduction in nodules and abscesses was observed, with 17 subjects achieving a 50% or greater improvement in HS Clinical Response Score (HiSCR) by week 4. Of these patients, 85% achieved HiSCR 50 at week 12, 70% achieved HiSCR 75 and 25% achieved HiSCR 90.

“The rapid and significant clinical response in the first 4 weeks of therapy suggests that SYK may be a potential therapeutic target in HS,” the authors wrote. “SYK antagonism provides a temporary clinical benefit in HS and further benefit may be seen by future combined therapy with other therapeutic agents.”