Journal Article Ahead of print
PubMed: 42200380 DOI: 10.1111/jdv.70510
Tocilizumab for severe and refractory mucous membrane pemphigoid.
J Eur Acad Dermatol Venereol
Authors: Billal Tedbirt, Maud Maho-Vaillant, Julie Gueudry, Marie-Laure Golinski, Marion Marcaillou, Blanche Bergeret, Guillaume Chambon, Pierre Bouchetemble, Soumeya Bekri, Abdellah Tebani, Hervé Maillard, Cécile Morice, Anais Vautier, Edgar-Pierre Libert, Christelle Le Roux-Villet, Marion Carrette, Olivier Boyer, Vivien Hébert, Sébastien Calbo, André Gillibert, Pascal Joly
Affiliations
- Department of Dermatology, French Reference Center for Auto Immune Blistering Diseases, Rouen University Hospital, Normandie University, Rouen, France.
- Univ Rouen Normandie, Inserm, Normandie Univ, PANTHER UMR 1234, Rouen, France.
- Department of Ophthalmology, Rouen University Hospital, Rouen, France.
- Department of Dermatology, Toulouse University Hospital, Toulouse, France.
- Department of Dermatology, CHU Nîmes, Nîmes, France.
- Department of Otolaryngology-Head and Neck Surgery, CHU Nîmes, Nîmes, France.
- Department of Otolaryngology-Head and Neck Surgery, CHU Rouen, Rouen, France.
- Department of Metabolic Biochemistry, Normandie University, UNIROUEN, INSERM U1245, CHU Rouen, Rouen, France.
- Department of Dermatology, Hôpital du Mans, Le Mans, France.
- Department of Dermatology, CHU Caen, Caen, France.
- Department of Ophthalmology, Angers University Hospital, Angers, France.
- Department of Dermatology, Angers University Hospital, Angers, France.
- Department of Dermatology & Reference Center for Autoimmune Bullous Diseases, Avicenne University Hospital, AP-HP, Sorbonne-Paris-Nord University, Bobigny, France.
- Department of Immunology and Biotherapy, Rouen University Hospital, Rouen, France.
- Department of Biostatistics, CHU Rouen, Rouen, France.
Abstract
BACKGROUND
Mucous membrane pemphigoid (MMP) is a rare autoimmune blistering disease involving mucous membranes with a potentially devastating fibrosing course. Laryngotracheal and/or oesophageal involvement may lead to life-threatening complications, while corneal involvement may lead to blindness.
OBJECTIVES
To characterize the serum cytokine profile of MMP and to evaluate the efficacy of tocilizumab in nine cases of severe MMP according to the serum levels of IL-6.
METHODS
Sera from MMP patients were compared to sex- and age-matched healthy donors (HD) and patients with bullous pemphigoid (BP), using two proteomic assays (Olink and Luminex). The Olink assay included 40 MMP, 40 BP and 40 HD sera, and the Luminex assay included 63 MMP, 31 BP and 24 HD sera. Based on these findings, nine patients with severe and refractory MMP received tocilizumab on a compassionate use basis after failure of standard therapies.
RESULTS
Proteomic analyses revealed high serum levels of IL-6, IL-8, MIP-1α/CCL3 and MIP-1β/CCL4 in MMP compared to BP and HD. Patients with MMP who achieved complete remission during follow-up had lower baseline serum levels of IL-6 (p < 0.0001), IL-8 (p = 0.0382), MIP-1α/CCL3 (p = 0.0005) and MIP-1β/CCL4 (p = 0.0009) than those with persistent disease activity. Nine patients with severe and refractory MMP were treated with tocilizumab. Their mean MMPDAI score decreased from 14.8 ± 6.6 to 4.2 ± 3.2 (p = 0.009). At the last evaluation, seven patients (78%) were in partial remission, one (11%) in complete remission and one (11%) recently treated achieved control of disease activity. Baseline IL-6 was elevated in five of eight tested patients; all three with normal IL-6 levels improved clinically. Four non-severe adverse events were observed (two neutropenias, one thrombocytopenia, one hepatic cytolysis).
CONCLUSIONS
Proteomic analyses identified a distinct MMP cytokine profile with increased IL-6, IL-8, MIP-1α/CCL3 and MIP-1β/CCL4, supporting IL-6 targeting, with tocilizumab as a potential option in severe refractory MMP.
MeSH
Cytokines, Sexually Transmitted Diseases, Serum, Skin Diseases, Pemphigoid, Bullous, Proteomics, Mucous Membrane, Membranes