Therapy For Pemphigus Research Articles

Mechanisms of Resistance to Rituximab Used for the Treatment of Autoimmune Blistering Diseases

Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory.

EGFR Inhibition by Erlotinib Rescues Desmosome Ultrastructure and Keratin Anchorage and Protects against Pemphigus Vulgaris IgG–Induced Acantholysis in Human Epidermis

Pemphigus is a severe blistering disease caused by autoantibodies primarily against the desmosomal cadherins desmoglein (DSG)1 and DSG3 which impair desmosome integrity. Especially for the acute phase, additional treatment options allowing to reduce corticosteroids would fulfill an unmet medical need. Here, we provide evidence that epidermal growth factor receptor (EGFR) inhibition by erlotinib ameliorates pemphigus vulgaris immunoglobulin G (PV-IgG) -induced acantholysis in intact human epidermis. PV-IgG caused phosphorylation of EGFR (Y845) and SRC in human epidermis. In line with that, a phosphotyrosine kinome analysis revealed a robust response associated with EGFR and SRC family kinase signaling in response to PV-IgG but not pemphigus foliaceus autoantibodies. Erlotinib inhibited PV-IgG-induced epidermal blistering and EGFR phosphorylation, loss of desmosomes as well as ultrastructural alterations of desmosome size, plaque symmetry, keratin filament insertion and restored the desmosome midline considered as hallmark of mature desmosomes. Erlotinib enhanced both single molecule DSG3 binding frequency and strength and delayed DSG3 fluorescence recovery supporting that EGFR inhibition increases DSG3 availability and cytoskeletal anchorage. Our data indicate that EGFR is a promising target for pemphigus therapy due to its link to several signaling pathways known to be involved in pemphigus pathogenesis.

Comparing Clinical Outcomes of Steroid-Sparing Therapy With Rituximab Versus Rituximab Alone in Pemphigus.

Previous clinical trials have demonstrated that rituximab therapy combined with conventional steroid-sparing therapy (SST) has increased rates of disease control for mucous membrane pemphigoid compared with rituximab alone. However, limited data is available regarding the role of SST with rituximab therapy in pemphigus. This study aimed to examine clinical outcomes in pemphigus patients treated with rituximab with SST versus without the addition of SST. A retrospective chart review was performed for adult pemphigus patients in the Southeastern US at Emory between January 1, 2011, and December 31, 2021. Primary outcomes, including time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, and time to relapse after a rituximab cycle, were compared between patients on SST and patients without SST.  Results: Following rituximab therapy, there was no difference in time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, or time to relapse for patients with or without SST. Our study is limited by its retrospective decline, setting at a single academic center, and inclusion of a high proportion of patients with moderate disease. The use of SST with rituximab dosing did not improve clinical outcomes related to time to remission, reduction in prednisone dosing, or relapse. These data provide further evidence for the use of rituximab in the majority of pemphigus patients without the need for SST. J Drugs Dermatol. 2024;23(3):e97-e99    doi:10.36849/JDD.7949e.

VARICELLA-ZOSTER VIRUS INFECTION IN A PATIENT 12 DAYS POST RITUXIMAB: UNUSUAL CO-PRESENTATION OF SHINGLES AND CHICKENPOX

Rituximab, an anti CD20 monoclonal antibody, is used in the management of lymphoproliferative and autoimmune conditions such as pemphigus. As an immunosuppressor, it exposes patients to an increased risk of infection. Two cases of varicella-zoster virus infection post Rituximab were been reported in literature. The coexistence of chickenpox (primary infection) and shingles (reactivation of latent infection) in the same patient has never been reported in the literature, especially after rituximab treatment. Herein we present the first case of association of these 2 manifestations in a patient 12 days after rituximab therapy for pemphigus.

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

Une bradycardie à … l’effort !

Pemphigus is a rare autoimmune disease, which could be fatal without treatment. Recently, target therapy is increasingly being used in different autoimmune diseases. However, there are limited studies associated with target therapy in pemphigus. In this study, it was tried to identify the role of interleukin (IL) -21 in patients with pemphigus. Based on the available studies on the role of IL-21 associated with several cells, including T cells, B cells, natural killer (NK) cells, natural killer T (NKT) cells, mast cells as well as regulatory B cells and regulatory T cells, the possible roles of this cytokine in pemphigus were discussed in detail. It was found that IL-21 is a crucial cytokine associated with pemphigus disease, which has not been discussed in this disease yet. It is able to promote T helper (Th) 2, Th17, T follicular helper (Tfh), CD8 + cytotoxic T lymphocytes (CTLs), NK and NKT cells. It also causes the production of immunoglobulin (Ig)G in addition to the decrease of Tregs. All the mentioned alterations seem to be involved in disease progression via different signaling pathways. Inhibition of these changes must cause improvement of disease severity. By inhibition of IL-21 or its receptor, it is expected that patients with severe pemphigus experience relative and gradual improvement. This inhibition could be induced by tofacitinib, which was approved by the US Food and Drug Administration as a treatment for rheumatoid arthritis patients, or anti-IL-21 monoclonal antibody, NNC114-0006. However, more studies are needed to confirm it as a promising therapy.

B-cell targeted therapy of pemphigus.

Pemphigus is an autoimmune disease that causes blistering and erosion of the skin and mucous membranes because of autoantibodies against desmoglein, which plays an important role in adhesion between epidermal keratinocytes. Treatment of pemphigus has long been centered on corticosteroids, and the guidelines for management of pemphigus have recommended high-dose systemic corticosteroids as the first-line treatment. While guideline-based treatment has been shown to be beneficial in patients with pemphigus, it has also become clear that this treatment is accompanied by significant burden and risk. The challenge for future pemphigus treatment is to maximize efficacy while minimizing risk during the course of the disease. In this regard, treatment targeting B cells is expected to become increasingly important as autoreactive B cells in pemphigus patients are thought to play a major role in the production of autoantibodies, which form the basis of the pathogenesis. The recent expansion of insurance coverage to rituximab, a monoclonal antibody against CD20, for refractory pemphigus in the USA, Europe, and Japan has opened up a new era of pemphigus treatment by enabling treatment strategies with drugs targeting B cells in patients. Here, we discuss the current status and future prospects of pemphigus treatment, focusing on rituximab and Bruton's tyrosine kinase inhibitors, which are expected to become essential drugs for pemphigus treatment in the future.

Disease progression and response to therapy in pemphigus based on a registry.

Pemphigus diseases are potentially life-threatening and rare autoimmune bullous disorders characterized by blisters and erosions of the skin and mucous membranes. These disorders can be largely divided into two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The objective of this study was to evaluate the autoantibody profile and response to therapy of PV and PF patients by analyzing the clinicopathological data from a registry for bullous autoimmune dermatoses. In a retrospective study, data from 69 patients with PV and PF were included in the analysis. The Autoimmune Bullous Skin Intensity Score (ABSIS) was used to assess the clinical course, remissions, relapses and severity of the disease at first manifestation and throughout the observation period. ELISA was performed to assess levels of anti-desmoglein (Dsg)-1 and anti-Dsg3 IgG serum autoantibodies. The mean remission time in PV and PF patients was 63 weeks. PV patients with mucosal involvement showed a more favorable healing process. In PV patients with a moderate/high anti-Dsg1 IgG serum level at baseline, anti-Dsg3 IgG levels decreased during the observation period. Our study provides additional insights into the clinical course of patients with PV and PF, revealing that a mucosal phenotype is associated with a higher tendency towards remission.

Experience of Rituximab Therapy in Pemphigus: A Three-Year Retrospective Study from a Sub-Himalayan State.

Pemphigus is a group of auto-immune blistering disorders, characterised clinically by mucocutaneous blisters and erosions and histopathologically by intra-epidermal acantholysis. It was traditionally associated with high morbidity and mortality. The use of rituximab has brought upon a new dawn in the treatment of pemphigus. A retrospective analysis to ascertain the efficacy, tolerance, adverse effect profile, remission, and relapse with the use of rituximab. A retrospective analysis of all diagnosed pemphigus patients who received rituximab therapy over a period of 3 years was performed. The patient's baseline characteristics, disease duration, clinical presentations, mucosal involvement, disease-severity assessment, and adverse events with rituximab were noted. The outcomes were evaluated based on the definitions of the disease-outcome parameters as early and late endpoints. Of the 17 pemphigus patients, there were 14 females (82.4%) and three males (17.6%) with a mean age of 35.9 ± 16.5 years (range: 9-65 years). Pemphigus vulgaris (PV) was the predominant type in 11 (64.7%) patients. After rituximab infusion, the 17 patients attained the end of consolidation phase (ECP) within 15 days to 3 months, and the mean duration was 1.24 months. The complete remission (CR on/off) ranged from 0.5 to 35 months, and the mean duration of remission was 21.7 months. Within a median time of 4.2 months, almost 80% patients achieved CR on therapy. Nine (53%) patients were in CR without any therapy till the end of the study period, and eight (47%) were in remission while on minimal therapy. Rituximab is an efficacious therapeutic agent for pemphigus and is better tolerated and safer to all the previous medications used in the treatment.

Lights and Shadows of Rituximab in Dermatology

Rituximab is a CD 20 monoclonal antibody drug used in various spectrum of diseases today. It has proven to be a boon, especially in the field of dermatology. Although Rituximab was initially introduced as a novel method to treat B-cell Non Hodgkin Lymphoma, its use has rapidly expanded to include a number of other Lymphomas and Autoimmune diseases.This review is to give a bird’s eye view of updates on rituximab.
 Conclusion: With its horizons expanding in dermatology, and with better information regarding its efficacy and safety profile, Rituximab has now become an approved first‑line therapy for pemphigus. In conclusion, Rituximab has proven to be a substantial boon for dermatologists in difficult to treat cases.

Multiple cycles of rituximab therapy for pemphigus: A group of patients with difficult- to-treat disease or a consequence of late rituximab initiation?

Pemphigus is a serious autoimmune disease with few appropriate therapeutic options. Although rituximab (RTX) has recently shown great promise in this regard, the best protocol of its administration is remains to be elucidated. This study aimed to evaluate the patients who need at least 3 cycles of treatment with RTX to identify hard-to-treat patients' characteristics, which might lead to consider more prompt protocols for treatment of them. A retrospective cross-sectional study was conducted on 45 patients with pemphigus vulgaris who received at least 3 cycles of RTX. Their demographic, clinical, and laboratory data as well as details of treatment protocol and final clinical situation of patients were evaluated. Totally, 45 patients (21 men and 24 women) with mean age of 44.33 years were included in this paper. Women were about 8 years older than men (mean age: 48.1 years versus 40.1 years, p: 0.011) and needed RTX approximately 2 years later in their course of disease (gap: 41.04 months vs. 14.85 months, p: 0.003). Buccal, truncal, and scalp regions were the most frequent sites of involvement respectively. A significant decrease in both anti-Dsg1, 3 was seen at last visit compared to baseline. However, the amount of this decrement was not significantly different between them (p: 0.083). Partial remission in 31.11%, complete remission in 24.44%, relapse in 15.56%, partial remission on treatment in 15.56% and complete remission on treatment in 13.33% were seen at the last follow-up session. RTX is an effective medication for PV even in patients with refractory disease and its therapeutic effect is increased with each subsequent cycle. Male gender, severe oral mucosal involvement on disease onset and extensive scalp and truncal lesions as first cutaneous manifestation of disease are more likely to be signs of refractory PV. Hence, it is reasonable to consider more prompt protocols for treatment of these cases. Moreover, late prescription of RTX during the course of disease might play a role in presence of more resistant form of disease.

Treatment of pemphigus vulgaris and foliaceus with efgartigimod, a neonatal Fc receptor inhibitor: a phase II multicentre, open‐label feasibility trial*

Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoimmune disorders triggered by IgG autoantibodies against mucosal and epidermal desmogleins. There is an unmet need for fast-acting drugs that enable patients to achieve early sustained remission with reduced corticosteroid reliance. To investigate efgartigimod, an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor, thereby reducing serum IgG levels, for treating pemphigus. Thirty-four patients with mild-to-moderate pemphigus vulgaris or foliaceus were enrolled in an open-label phase II adaptive trial. In sequential cohorts, efgartigimod was dosed at 10 or 25mgkg-1 intravenously with various dosing frequencies, as monotherapy or as add-on therapy to low-dose oral prednisone. Safety endpoints comprised the primary outcome. The study is registered at ClinicalTrials.gov (identifier NCT03334058). Adverse events were mostly mild and were reported by 16 of 19 (84%) patients receiving efgartigimod 10mgkg-1 and 13 of 15 (87%) patients receiving 25mgkg-1 , with similar adverse event profiles between dose groups. A major decrease in serum total IgG and anti-desmoglein autoantibodies was observed and correlated with improved Pemphigus Disease Area Index scores. Efgartigimod, as monotherapy or combined with prednisone, demonstrated early disease control in 28 of 31 (90%) patients after a median of 17days. Optimized, prolonged treatment with efgartigimod in combination with a median dose of prednisone 0·26mgkg-1 per day (range 0·06-0·48) led to complete clinical remission in 14 of 22 (64%) patients within 2-41weeks. Efgartigimod was well tolerated and exhibited an early effect on disease activity and outcome parameters, providing support for further evaluation as a therapy for pemphigus.

Comorbid mental health issues in patients with pemphigus vulgaris and pemphigus foliaceus.

The term 'pemphigus' refers to chronic autoimmune skin disorders that cause blistering erosions on the skin and oral mucosa. The two major clinical forms are pemphigus vulgaris and pemphigus foliaceus. Although rare, they confer a stark symptomatic burden upon patients that significantly impacts daily life. Comorbid mental health issues are not routinely screened for in patients with pemphigus, and current UK guidance provides no formal provision for the identification and treatment of psychological issues. This review is the first of its kind, to our knowledge, to systematically examine the available evidence on mental health issues in pemphigus. Published work suggests that the incidence of anxiety and depression is much higher in patients with pemphigus compared with both the general population and with patients having other chronic skin disorders. Disease severity appears to be closely linked to mental health, with worsening of pemphigus associated with deteriorations in psychological wellbeing. Corticosteroids, which are associated with depression in chronic use, are the current first-line therapy for pemphigus and have been identified as a potential confounder and independent risk factor for mental health comorbidity in pemphigus. Current evidence is unclear whether a bidirectional relationship exists between mental health and pemphigus severity, and more thorough research is required to develop understanding of this issue. In conclusion, we have identified a high incidence of mental health comorbidity in pemphigus, and recommend routine screening of patients with pemphigus for mental health issues and signposting toward mental health services as an initial measure to address this.

Autoantibody-Specific Signalling in Pemphigus.

Pemphigus is a severe autoimmune disease impairing barrier functions of epidermis and mucosa. Autoantibodies primarily target the desmosomal adhesion molecules desmoglein (Dsg) 1 and Dsg 3 and induce loss of desmosomal adhesion. Strikingly, autoantibody profiles in pemphigus correlate with clinical phenotypes. Mucosal-dominant pemphigus vulgaris (PV) is characterised by autoantibodies (PV-IgG) against Dsg3 whereas epidermal blistering in PV and pemphigus foliaceus (PF) is associated with autoantibodies against Dsg1. Therapy in pemphigus is evolving towards specific suppression of autoantibody formation and autoantibody depletion. Nevertheless, during the acute phase and relapses of the disease additional treatment options to stabilise desmosomes and thereby rescue keratinocyte adhesion would be beneficial. Therefore, the mechanisms by which autoantibodies interfere with adhesion of desmosomes need to be characterised in detail. Besides direct inhibition of Dsg adhesion, autoantibodies engage signalling pathways interfering with different steps of desmosome turn-over. With this respect, recent data indicate that autoantibodies induce separate signalling responses in keratinocytes via specific signalling complexes organised by Dsg1 and Dsg3 which transfer the signal of autoantibody binding into the cell. This hypothesis may also explain the different clinical pemphigus phenotypes.

Comparison of Guidelines for Management of Pemphigus: a Review of Systemic Corticosteroids, Rituximab, and Other Immunosuppressive Therapies.

Pemphigus is a severe autoimmune bullous dermatosis that affects the skin and/or mucosa, and it may be life-threatening without proper treatment. The guidelines and/or consensus statements for treatment vary widely between groups. We selected 6 guidelines and consensus statements established by different associations about the management of pemphigus vulgaris (PV) and/or pemphigus foliaceus (PF) to review, compare, and contrast the similarities and differences of these recommendations and provide optimal management suggestions to physicians. Corticosteroids remain a first-line therapy for pemphigus, but there are many differences in initial dose, tapering schedule, and management of relapse between different guidelines. Rituximab is a monoclonal antibody targeting CD20-positive B lymphocytes that is approved as a first-line therapy in moderate-to-severe pemphigus. Immunosuppressive agents, such as azathioprine (AZA) and mycophenolate mofetil (MMF), are also widely used as corticosteroid-sparing drugs, but the adjuvant applications and dosage regimens of different recommendations are not standardized. We attribute these differences to the clinical scoring adopted, the standards for disease severity evaluation, the publication year of each guideline, and local and regional healthcare differences.

B-cell targeted therapies in pemphigus.

Pemphigus is a rare autoimmune disease of the skin, characterized by autoantibodies targeting adhesion proteins of the epidermis, in particular desmoglein 3 and desmoglein 1, that cause the loss of cell-cell adhesion and the formation of intraepidermal blisters. Given that these autoantibodies are both necessary and sufficient for pemphigus to occur, the goal of pemphigus therapy is the elimination of autoreactive B-cells responsible for autoantibody production. Rituximab, an anti-CD20 monoclonal antibody, was the first targeted B-cell therapy approved for use in pemphigus and is now considered the frontline therapy for new onset disease. One limitation of this treatment is that it targets both autoreactive and non -autoreactive B-cells, which accounts for the increased risk of serious infections in treated patients. In addition, most rituximab-treated patients experience disease relapse, highlighting the need of new therapeutic options. This review provides a concise overview of rituximab use in pemphigus and discusses new B-cell and antibody-directed therapies undergoing investigation in clinical studies.

National trends in incidence, mortality, hospitalizations, and expenditures for pemphigus in Taiwan

BackgroundData on trends in epidemiological characteristics and economic burden of pemphigus are scarce. ObjectiveTo describe national trends in pemphigus’ incidence, mortality, hospitalizations, and expenditures between 2003 and 2015 in Taiwan. MethodsThis nationwide study used the Taiwan National Health Insurance Research Database to identify pemphigus patients from 2003 to 2015. Annual incidence, prevalence, healthcare utilization, and expenditure trends were calculated and analyzed. ResultsPemphigus’ incidence increased significantly from 3.19 to 4.70 per million person-years in 2003–2010 but fluctuated in 2011−2015. Pemphigus patients had higher mortality and care costs. Medical utilization and expenditure declined for pemphigus inpatients and outpatients. Systemic corticosteroid use decreased, but mortality remained stable. ConclusionThe health expense reduction for pemphigus was mainly attributed to decreased utilization, length of stay, and inpatient costs. The persistently elevated mortality rate highlights an unmet need in pemphigus therapy.

Successful treatment with thalidomide for pemphigus vulgaris.

Background:Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune blistering disease characterized by suprabasal acantholysis, causing painful mucocutaneous blisters and erosions. Current mainstay therapy for pemphigus is systemic corticosteroids in combination with or without immunosuppressive adjuvants, which may cause severe adverse effects and seriously impact on the quality of life in pemphigus patients. The objective of this study was to evaluate the efficacy and safety of thalidomide therapy in patients with PV.Methods:This study examined six PV patients from June 5, 2017, to November 11, 2018, in the dermatology department of Peking Union Medical College Hospital. Treatment with thalidomide was applied at a dose of 50–100 mg/day for disease control.Results:The mean age of the six patients (two male and four female patients) at the time of thalidomide therapy initiation was 50.2 years (range: 38–67 years), and the total duration of follow-up after thalidomide therapy was 13.2 months (range: 5–25 months). All patients responded favorably to thalidomide treatment, and three patients showed a dramatic reduction in anti-Dsg3 autoantibodies in the serologic examinations within 1 year. Five patients were found to have mucosal involvement. Mild adverse effects were noted in three patients, which could be managed after the application of symptomatic treatment and did not interfere with the pemphigus therapy.Conclusion:These results demonstrate that thalidomide could be an effective and safe option for PV patients, especially those who are concerned about steroid-induced severe complications, and have mucosal diseases.

A New Solid-Phase Immunosorbent for Selective Binding of Desmoglein 3 Autoantibodies in Patients with Pemphigus Vulgaris.

Autoantibodies, immunoglobulins G (IgG) against the desmosomal proteins desmogleins 1 and 3, play a significant role in the pathogenesis of pemphigus vulgaris. The basic therapy for pemfigus includes systemic corticosteroids, but their use should be as brief as possible because of the severe side effects. In cases of corticosteroid- resistant pemfigus, adjuvant therapy, in particular extracorporeal methods, is used. The most effective and safest extracorporeal therapy is immunosorbtion. Immunosorbtion is based on the removal of pemphigus antibodies from the blood using an affinity sorbent during a therapeutic apheresis procedure. Existing immunosorbents are nonselective and increase the risk of infection. We designed an immunosorbent based on an agarose matrix, Affi-Gel 15, and human recombinant desmoglein 3, as a ligand, for a selective removal of autoantibodies from pemphigus patients’ sera. It was shown on a pemphigus experimental model in vivo (neonatal Balb/c mouse model) and in vitro that the immunosorbent can effectively remove desmoglein 3-associated autoantibodies. The experimental results demonstrate that the solid-phase matrix immunosorbent Affi-Gel 15–Dsg3 is a promising product for the development of pemphigus therapy.

Factors Associated With Complete Remission After Rituximab Therapy for Pemphigus

Rituximab has emerged as a front-line therapy for pemphigus, but prognostic factors for achieving complete remission off therapy (CROT) with oral systemic agents remain unknown. To describe rates of CROT and relapse and identify prognostic factors for achieving CROT after rituximab therapy for pemphigus. A single-center, retrospective, cohort study was conducted at the University of Pennsylvania including 112 patients with pemphigus treated with rituximab with at least 12 months' clinical follow-up after the start of rituximab therapy. Multivariate regression analysis of factors predictive of CROT and Kaplan-Meier analysis of disease relapse were conducted. The study included patients treated with rituximab from March 15, 2005, until December 19, 2016. Data analysis was performed from December 2017 to June 2018. The primary study outcome was CROT after 1 cycle. Secondary study outcomes included rate of CROT or the composite end point of CROT or complete remission on minimal therapy after 1 or more cycle, and median time to relapse. Multivariate regression analysis for prognostic variables for CROT, including age, sex, pemphigus subtype, body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared), disease duration, and dosing regimen, was performed. A total of 112 patients with pemphigus with median 37.8 months (range, 12.1-130.7) follow-up after rituximab therapy were identified. Of these, 65 were women (58.0%). At the time of first rituximab infusion, median age was 52.3 years (range, 20.0-89.3). Including patients who received multiple cycles of rituximab, 79 patients (70.5%) achieved CROT after a median time of 10.5 months (range, 2.0-49.8), and 36 of 72 patients (50.0%) subsequently experienced relapse after a median of 23.3 months (interquartile range, 10.8-50.4 months). Considering only the first cycle of rituximab, 54 patients (48.2%) achieved CROT. Controlling for age, sex, pemphigus subtype, BMI, and disease duration, patients who received lymphoma vs rheumatoid arthritis dosing were 2.70-fold more likely to achieve CROT (odds ratio [OR], 2.70; 95% CI, 1.03-7.12; P = .04). Increasing age was associated with significant increases in achieving CROT (Wald test for trend, P = .01), whereas BMI greater than or equal to 35 was associated with a 0.14 OR (95% CI, 0.03-0.63; P = .01) for achieving CROT, regardless of the dosing regimen. In multivariate analysis, there was no significant difference in CROT rates with sex (OR, 1.01; 95% CI, 0.42-2.50; P = .97), pemphigus subtype (OR, 0.37; 95% CI, 0.09-1.51; P = .17), or disease duration (OR, 0.99; 95% CI, 0.98-1.00; P = .09). Lymphoma dosing and older age may be associated with CROT and BMI greater than or equal to 35 may be a negative prognostic factor for CROT after rituximab therapy for pemphigus. These findings help inform clinical expectations and merit evaluation in future prospective clinical trials.