TY - JOUR
TI - Proof of concept for the clinical effects of oral rilzabrutinib, the
first Bruton tyrosine kinase inhibitor for pemphigus vulgaris: the phase
II BELIEVE study
AU - Murrell, D. F.
AU - Patsatsi, A.
AU - Stavropoulos, P.
AU - Baum, S. and
AU - Zeeli, T.
AU - Kern, J. S.
AU - Roussaki-Schulze, A. -V.
AU - Sinclair, R.
AU - and Bassukas, I. D.
AU - Thomas, D.
AU - Neale, A.
AU - Arora, P.
AU - Caux,
AU - F.
AU - Werth, V. P.
AU - Gourlay, S. G.
AU - Joly, P.
AU - BELIEVE Trial
AU - Investigators
JO - British Journal of Dermatology
PY - 2021
VL - 185
TODO - 4
SP - 745-755
PB - Wiley
SN - 0007-0963, 1365-2133
TODO - 10.1111/bjd.20431
TODO - null
TODO - 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.
ER -