@article{3029358,
    title = "Proof of concept for the clinical effects of oral rilzabrutinib, the
first Bruton tyrosine kinase inhibitor for pemphigus vulgaris: the phase
II BELIEVE study",
    author = "Murrell, D. F. and Patsatsi, A. and Stavropoulos, P. and Baum, S. and and Zeeli, T. and Kern, J. S. and Roussaki-Schulze, A. -V. and Sinclair, R. and and Bassukas, I. D. and Thomas, D. and Neale, A. and Arora, P. and Caux, and F. and Werth, V. P. and Gourlay, S. G. and Joly, P. and BELIEVE Trial and Investigators",
    journal = "British Journal of Dermatology",
    year = "2021",
    volume = "185",
    number = "4",
    pages = "745-755",
    publisher = "Wiley",
    issn = "0007-0963, 1365-2133",
    doi = "10.1111/bjd.20431",
    abstract = "Background Bruton tyrosine kinase (BTK) inhibition targets B-cell and
other non-T-cell immune cells implicated in the pathophysiology of
pemphigus, an autoimmune disease driven by anti-desmoglein
autoantibodies. Rilzabrutinib is a new reversible, covalent BTK
inhibitor demonstrating preclinical efficacy as monotherapy in canine
pemphigus foliaceus.
Objectives To evaluate the efficacy and safety of oral rilzabrutinib in
patients with pemphigus vulgaris in a multicentre, proof-of-concept,
phase II trial.
Methods Patients with Pemphigus Disease Area Index severity scores 8-45
received 12 weeks of oral rilzabrutinib 400-600 mg twice daily and 12
weeks of follow-up. Patients initially received between 0 and <= 0
center dot 5 mg kg(-1) prednisone-equivalent corticosteroid (CS; i.e.
‘low dose’), tapered after control of disease activity (CDA; no new
lesions, existing lesions healing). The primary endpoints were CDA
within 4 weeks on zero-to-low-dose CS and safety.
Results In total, 27 patients with pemphigus vulgaris were included:
nine newly diagnosed (33%) and 18 relapsing (67%); 11 had moderate
disease (41%) and 16 moderate to severe (59%). The primary endpoint,
CDA, was achieved in 14 patients (52%, 95% confidence interval 32-71):
11 using low-dose CS and three using no CS. Over 12 weeks of treatment,
mean CS doses reduced from 20 center dot 0 to 11 center dot 8 mg per day
for newly diagnosed patients and from 10 center dot 3 to 7 center dot 8
mg per day for relapsing patients. Six patients (22%) achieved complete
response by week 24, including four (15%) by week 12. Treatment-related
adverse events were mostly mild (grade 1 or 2); one patient experienced
grade 3 cellulitis.
Conclusions Rilzabrutinib alone, or with much lower CS doses than usual,
was safe, with rapid clinical activity in pemphigus vulgaris. These data
suggest that BTK inhibition may be a promising treatment strategy and
support further investigation of rilzabrutinib for the treatment of
pemphigus."
}