Rapid Disease Control in First-Line Therapy-Resistant Mucous Membrane Pemphigoid and Bullous Pemphigoid with Omalizumab as Add-On Therapy: A Case Series Of 13 Patients

Abstract

The role of IgE autoantibodies has been demonstrated in the pathogenesis of bullous pemphigoid for many years. Recently, omalizumab (OMZ), a humanized monoclonal anti-IgE antibody that depletes total serum IgE, has been used off-label in a few case series of bullous pemphigoids demonstrating a rapid efficacy and allowing significant improvements or complete remission as add-on therapy in first-line treatment-resistant patients. Herein, we report the largest retrospective study to evaluate OMZ effectiveness in patients with subepidermal autoimmune blistering diseases. Our series included 13 patients from a single center with bullous pemphigoid or mucous membrane pemphigoid, of whom 7 had mucous membrane involvement. OMZ was added to the unchanged immunosuppressive therapies. Detailed clinical and immunological data during the first year were collected, notably for specific anti-BP180-NC16A IgE and IgG, and the median total follow-up was 30 months (range: 3–81). Our series demonstrated that OMZ induced a significant improvement in pruritus, urticarial score, and daily blister count on day 15, allowing disease control to be achieved in a 1-month median time and complete remission (CR) in a 3-month median time in 85% of these patients previously in therapeutic impasse. At the end of the follow-up, 31% of patients achieved CR on minimal therapy after OMZ weaning without relapses, and 54% achieved CR on OMZ continuation with a minimal dose of concomitant treatment. Two patients experienced therapeutic failure (15%). At baseline, clinical variables reflecting activity were significantly positively correlated with eosinophil blood count, total IgE serum level, specific anti-BP180 IgE and IgG. While baseline anti-BP180 IgG and specific anti-BP180 IgE were significantly positively correlated, only the two patients who experienced a therapeutic failure with OMZ did not fit with this correlation, demonstrating elevated levels of anti-BP180 IgG with no measurable BP180-specific IgE. Follow-up of immunological variables demonstrated a rapid decrease of eosinophilia towards normalization, whereas a slower decline towards negativation was observed over 1 year for anti-BP180 IgG and anti BP180 IgE in patients who responded to OMZ. This case series demonstrated that OMZ is a rapidly effective biologic therapy for refractory bullous pemphigoid and mucous membrane pemphigoid, permitting rapid disease control and reduction of concomitant therapeutics.

Bullous Pemphygoid and Novel Therapeutic Approaches

“…Other studies reported variable data on the value of specific IgE in BP, differing from 22% to 100% [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. This variation could also be attributable to the lack of standardization in methods used for detection with different sensitivities.…”

“…Another case series reports high levels of liver enzymes and thrombocytopenia. Two patients developed a mild flu-like illness after injection, which was easily managed with paracetamol and disappeared from the sixth injection onwards [ 50 , 78 , 87 ].…”

Case report: Minimal manifestations of mucous membrane pemphigoid in a young adult

“…Instead of dapsone, classical immunosuppressants as mycophenolate or azathioprin can be employed, while rituximab is considered an off-label ultima ratio, especially in severely scarring courses ( 19 – 21 ). Finally, other approaches with intravenous immunoglobulins or omalizumab have been reported to be useful as well ( 22 , 23 ).…”

Adaptive and innate immune pathogenesis of bullous pemphigoid: A review

“…IgE-mediated autoimmunity may be involved in BP blister development ( 28 , 29 ). IgE autoantibodies target the intracellular domain of BP180.…”