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.

Keywords: Anti-BP180 IgE; Anti-BP180 IgG; Immunoglobulin E (IgE); autoimmune bullous diseases (AIBDs); autoimmune skin diseases; bullous pemphigoid (BP); mucous membrane pemphigoid (MMP); omalizumab (Xolair).

Figure 1

Flow diagram for the literature review on BP/MMP cases treated with omalizumab.

Figure 2

Dramatic improvement of daily blister count, pruritus visual analog score (PVAS) and urticaria score between baseline (blue) and the 15^th day after omalizumab therapy (purple). Data are presented as box and whisker plots showing extreme values, interquartile ranges, and medians. **p < 0.01, ***p < 0.001 (Wilcoxon signed–rank test).

Figure 3

Clinical improvement during omalizumab therapy. Case #2 at baseline (A) and day 15 (B); case #9 at baseline (C) and day 30 (D); case #11 at baseline (E) and day 30 (F).

Figure 4

Clinical and laboratory variables during the first year after omalizumab therapy in the 13 patients. Individual values through time on a linear scale (black: remittent patients, red: non–remittent patients): (A) Daily blister count, (B) Pruritus visual analogic score, (C) Urticaria score, (D) Eosinophil count, (E) BP180–NC16A IgG level, (F) BP180–NC16A IgE level over time for the 8 patients with measurable IgE auto–antibodies during follow–up, (G) Log–2 scale evolution of the mean values over time of eosinophil blood count, daily blister count, pruritus visual analogic score, and BP180–NC16A IgG.

Figure 5

Graphical representation of Spearman correlation matrix between clinical activity and immunological variables at baseline and outcomes. Red and blue colors indicate positive and negative correlations, respectively; the lighter the color, the less significant the corresponding correlation. The filled fraction of the circle in each pie chart corresponds to the absolute value of the associated Spearman correlation coefficient (r). *p < 0.05, **p < 0.01, ***p < 0.001, ¶ before omalizumab, † Time to complete remission.