Rituximab In Pemphigus Research Articles

Long-term metabolic and cardiovascular outcomes in patients treated with rituximab for pemphigus.

Long-term metabolic and cardiovascular outcomes in patients treated with rituximab for pemphigus.

Use of rituximab in pemphigus vulgaris/foliaceus patients during COVID-19 pandemic

Use of rituximab in pemphigus vulgaris/foliaceus patients during COVID-19 pandemic

Off-Label Uses of Rituximab in Dermatology.

Purpose of ReviewRituximab has transformed the treatment of B-cell malignancies and rheumatoid arthritis in the past 2 decades. More recently, this anti-CD20 monoclonal antibody has seen increasing usage in the field of dermatology. This review highlights the evidence supporting its use in several important dermatologic conditions.Recent FindingsKey recent findings include the 2018 FDA approval of rituximab for the treatment of moderate-to-severe pemphigus.SummaryData from randomized controlled trials have demonstrated the efficacy of rituximab in pemphigus, ANCA-associated vasculitis, and cryoglobulinemic vasculitis. More limited data suggests its use in recalcitrant cases of diseases such as pemphigoid, epidermolysis bullosa acquisita, and dermatomyositis. There is scarce evidence and mixed results for rituximab when studied in cutaneous polyarteritis nodosa and cutaneous lupus erythematosus.

Long-term efficacy and safety analysis of single cycle of biosimilar rituximab in pemphigus: A retrospective study of 76 patients from India.

Pemphigus poses a therapeutic challenge and rituximab is increasingly used in its treatment. Long-term data regarding efficacy and safety of rituximab in pemphigus is limited. This study was a retrospective analysis of 76 pemphigus patients with primary endpoint being the percentage of patients achieving complete remission (CR) on/off therapy. Secondary endpoints were time to relapse, mean cumulative dose of prednisolone after rituximab infusion, mean duration of follow up, and adverse events to rituximab if any. A total of 62 (82.7%) attained complete remission on/off treatment, out of which 42 were off therapy. Mean interval between rituximab administration and complete remission off treatment was 6.9± 3.7months. Complete remission off treatment was sustained for a mean duration of 21.4± 17.8months before relapse. Over a mean follow-up duration of 42.7± 24.9months (median 41, maximum 83 months), 22 of 62 patients (35.5%) who had achieved complete remission after the first cycle of rituximab relapsed. A mean total cumulative dose of 8716.3± 10533.8mg prednisolone was prescribed over a mean duration of 18.05 ± 15.64 months after the first cycle of rituximab. Adverse events were noted in 18 out of 76 patients (23.7%) which included infusion reactions (n= 3), minor infections (n= 7), transitory disease flare (n= 6), and mortality (n= 2). No statistically significant correlation was found between remission/relapse rates and age, gender or pemphigus subtype. This study substantiates the long-term efficacy and safety of single cycle of rituximab in pemphigus.

Clinical observation of different doses of rituximab for the treatment of severe pemphigus: A single-center prospective cohort study

To the Editor: Rituximab has been recommended as a first-line treatment for pemphigus, an autoimmune mucocutaneous disease.1 The conventional protocols of rituximab in pemphigus are commonly followed, including rituximab 1000 mg administered intravenously on days 1 and 15 or rituximab 375 mg/m2 administered intravenously once a week for 4 weeks, whereas small studies have proposed a low-dose protocol with rituximab 500 mg administered intravenously on days 1 and 15.2 Nevertheless, a lack of consensus on the dose and administration interval of rituximab in pemphigus remains.

The positive impact of rituximab on the quality of life and mental health in patients with pemphigus

To the Editor: Pemphigus is a group of chronic autoimmune blistering diseases affecting skin and mucosa with a huge impact on the quality of life (QOL).1-3 Although the efficacy and safety of rituximab in pemphigus are repeatedly shown, only few studies have investigated QOL and treatment burden. The objective of this study was to investigate the impact of rituximab on the general and treatment-specific QOL in pemphigus. This single-center observational study included patients with pemphigus treated with rituximab.

Rituximab in Pemphigus - An Observational Study from a Tertiary Care Center of North India.

Background:Pemphigus is a group of potentially fatal autoimmune mucocutaneous blistering diseases. Rituximab (RTX) is a chimeric anti-CD20 (anti-cluster of differentiate 20) monoclonal antibody being increasingly used and becoming the first-line therapy in the management of pemphigus.Aims and Objectives:This was an observational study to evaluate the efficacy and safety of rituximab in patients of pemphigus vulgaris (PV) who either did not respond or relapsed after conventional therapeutic regimens and in treatment naive pemphigus patients.Materials and Methods:The study included pemphigus patients coming to our immunobullous clinic who did not respond to conventional therapy or relapsed after receiving conventional therapy as well as fresh cases between January 2019 and October 2021. All enrolled patients received two doses of rituximab (1 gram in each) as intravenous infusions two weeks apart as per the rheumatoid arthritis protocol. The efficacy and safety were evaluated by assessing pemphigus area and activity score (PAAS) before and after the therapy, clinical response, and any adverse events during follow-up.Results:Sixteen (ten males and six females) patients were included in the study. The age of these patients ranged from 27 to 60 years, with a mean of 43.8 ± 9.8 years. There were 15 (93.75%) patients with PV (14 mucocutaneous type and 01 mucosal) and one (6.25%) with pemphigus foliaceus. Among these patients, nine (56.25%) were relapse cases, four (25%) were non-responders, and three (18.75%) were fresh cases who received rituximab as first-line therapy. Fourteen (87.5%) patients reached complete remission off therapy over a median time of 6.36 months (ranging from 18 weeks to 35 weeks). Rituximab was well-tolerated by our patients, and no serious adverse events were observed. The main limitation of our study was the small sample size and the lack of a comparison group.Conclusion:Rituximab is a safe and effective treatment for pemphigus.

Rituximab and Corticosteroid Effect on Desmoglein-Specific B Cells and Desmoglein-Specific T Follicular Helper Cells in Pemphigus

Pemphigus is an autoimmune blistering disease mediated by autoantibodies directed against desmogleins (DSGs). We recently showed that first-line treatment with rituximab (RTX) enables more patients to achieve long-lasting remission off therapy than corticosteroids alone. To understand the immunological mechanisms that mediate long-lasting clinical remission after RTX treatment, we analyzed the phenotype of DSG-specific memory B cells and DSG-specific T follicular helper cells by flow cytometry and measured antibody-secreting cells by enzyme-linked immune absorbent spot in patients treated with corticosteroids alone or RTX. This post hoc analysis of the RITUX3 trial showed that RTX induced a significant decrease of IgG-switched DSG-specific memory B cells. Accordingly, anti-DSG antibody-secreting cells were no longer detected in patients in complete remission after RTX. In contrast, corticosteroids did not modify the frequency or the phenotype of DSG-specific memory B cells, and anti-DSG antibody-secreting cells were still detected after treatment, even in patients in remission. Using peptide-HLADRB1∗0402 tetramer staining, we identified DSG-3-specific T follicular helper cells, which dramatically decreased after RTX, while remaining stable after corticosteroid treatment. Our findings suggest that long-lasting response to RTX in pemphigus relies on the decrease of DSG-specific circulating T follicular helper cells, which correlates with a sustained depletion of IgG-switched memory autoreactive B cells, leading to the disappearance of anti-DSG antibody-secreting cells.

Clinical and biological activity of rituximab in the treatment of pemphigus.

B-cells are major effector cells in autoimmunity since they differentiate into plasmocytes that produce pathogenic auto-antibody such as anti-desmoglein antibodies in pemphigus patients. Major advances were obtained using whole B-cell depleting therapies including anti-CD20 antibodies in refractory pemphigus patients that lead to rituximab approval in pemphigus patients in EU and USA. This review summarizes the data supporting the efficacy of rituximab in pemphigus and provides an overview of the reported immunological changes underlying its therapeutic action. Short and long-term remission in pemphigus is explained by the removal of autoreactive B-cells involved in the production of pathogenic IgG auto-antibodies and by enhancement of the appearance of regulatory B-cells that could maintain long term immune tolerance.

The effectiveness of rituximab in pemphigus and the benefit of additional maintenance infusions: Daily practice data from a retrospective study

The effectiveness of rituximab in pemphigus and the benefit of additional maintenance infusions: Daily practice data from a retrospective study

Effectiveness and safety analysis of rituximab in 146 Indian pemphigus patients: A retrospective single-center review of up to 68 months follow-up.

Rituximab is being increasingly used for the treatment of pemphigus. Data derived from single-center studies following a uniform treatment protocol are limited. Effect of demography and disease type on treatment response is poorly characterized. Our aim was to assess the effectiveness of biosimilar rituximab in pemphigus patients who had received rituximab as per rheumatoid arthritis protocol (2 doses, 1g each, infused 14 days apart). It was a retrospective review of 146 eligible patients to assess the proportion of patients achieving complete remission off treatment, time to achieve complete remission off treatment, proportion of patients who relapsed after achieving complete remission off treatment, time taken to relapse, duration and total cumulative dose of corticosteroids administered after rituximab. Additionally, we tried to find whether a correlation existed between age, gender, total duration of illness before rituximab and pemphigus disease type with the above-mentioned outcome measures. Of 146 patients, 107 (73.3%) attained complete remission off treatment. Mean interval between first dose rituximab administration and complete remission off treatment was 6.6 ± 3.4months. Complete remission off treatment was sustained for a mean duration of 9.1 ± 8.5 months before relapse. Over a mean follow-up duration of 24.9 ± 17.1 months (median 23, maximum 68 months), 75 of 107 patients (76.5%) who had achieved complete remission after first cycle of rituximab relapsed. A mean total cumulative dose of 3496 ± 2496 mg prednisolone was prescribed over a mean duration of 7.2 ± 4.7 months after first cycle of rituximab. Time taken to achieve remission was significantly longer in pemphigus foliaceus and these patients required significantly higher cumulative dose of prednisolone over a longer duration after rituximab. No deaths and long-term complications were recorded. Only clinical parameters were assessed. Immunological parameters including B-cell counts and enzyme-linked immunosorbent assay for anti-desmoglein antibody titers were not carried out. This study reinforces the beneficial role of rituximab in pemphigus. Pemphigus foliaceus patients required a higher total cumulative dose of prednisolone over a longer time to achieve remission and the remission lasted longer than that in pemphigus vulgaris.

A modified regimen of rituximab in pemphigus: A retrospective study

Introduction: Rituximab is a chimeric monoclonal antibody targeted against CD20 T-cells. It acts by the destruction of autoreactive B-cells. It is a common biologic agent widely used for the treatment of B-cell lymphoma, lymphoproliferative disorders, and inflammatory conditions that are refractory to conventional treatment, such as rheumatoid arthritis. However, various recent studies have shown an increasing number of serious adverse events associated with the use of rituximab, such as serious, often fatal, infusion reactions, infections, rigors, fever, peripheral edema, hypertension, myelosuppression, elevated transaminases, and cardiac failure. Only a few such studies have been performed in Indian patients, where Rituximab is still a new molecule. Aims: The aim of this study is to assess the efficacy and adverse events profile in patients with pemphigus group of diseases treated with rituximab. Materials and Methods: In this retrospective study, we analyzed records of 20 cases of pemphigus who received a modified rheumatoid arthritis (RA) protocol from January 2016 to June 2018, for the efficacy of rituximab as well as for the immediate and late adverse effects encountered with the use of rituximab. Results: It was found that 50% of cases achieved complete remission for the entire duration of follow up. The mean duration of remission was 8.55 months. More than 75% of patients relapsed only after 6 months. Twelve patients (60%) had various infusion reactions such as fever, chills, giddiness, breathlessness, bradycardia, and cyanosis. About 30% of the patients developed late side effects such as onychomycosis and sepsis. One of the patients died due to sepsis. Conclusions: Hence, we conclude that rituximab is still very effective at half the dose in the conventional RA protocol, and although it is a highly efficacious drug, it must be used with great caution, keeping in mind, these catastrophic side effects.

Rituximab as first line: an advent in pemphigus

<p class="abstract">Rituximab is a newly approved biological wonder drug in pemphigus vulgaris -an autoimmune mucocutaneous blistering disease due to antibodies produced against the epidermal adhesion molecules dsg 1 and dsg 2. The conventional therapy included high dose steroids or immunosuppressants that though effective had significant adverse effects that necessitated an alternate path in treatment. We present a case series of five patients in different clinical scenarios diagnosed with pemphigus vulgaris and treated with Rituximab by RA protocol either sole or in combination with other treatment strategies. Our experience with this drug has paved way to immense possibilities and outcomes that are in favour of using Rituximab as first line option. We have encountered prolonged remission in cases that were treated with Rituximab by Rheumatoid arthritis (RA) protocol. The sustained response has helped in reducing the dose of steroids and other immunosuppressants substantially. These facts are reinforced through our observations. But there is need to standardize the dosage of Rituximab in pemphigus.</p>

Rituximab therapy in pemphigus and other autoantibody-mediated diseases.

Rituximab, a monoclonal antibody targeting the B cell marker CD20, was initially approved in 1997 by the United States Food and Drug Administration (FDA) for the treatment of non-Hodgkin lymphoma. Since that time, rituximab has been FDA-approved for rheumatoid arthritis and vasculitides, such as granulomatosis with polyangiitis and microscopic polyangiitis. Additionally, rituximab has been used off-label in the treatment of numerous other autoimmune diseases, with notable success in pemphigus, an autoantibody-mediated skin blistering disease. The efficacy of rituximab therapy in pemphigus has spurred interest in its potential to treat other autoantibody-mediated diseases. This review summarizes the efficacy of rituximab in pemphigus and examines its off-label use in other select autoantibody-mediated diseases.

Clinical efficacy of rituximab in the treatment of pemphigus: A retrospective study.

Pulsed corticosteroids have been used successfully for the management of pemphigus. However, prolonged use of glucocorticoids may be associated with adverse effects and some patients show a poor response to conventional therapy. Biologics have shown a promising role in such cases; however, there is limited data from the Indian subcontinent. The primary objective was to assess the efficacy and adverse effects of rituximab in pemphigus. The secondary objective was to measure the cumulative doses of corticosteroids required for these patients. We undertook a retrospective review of records of 25 pemphigus patients (pemphigus vulgaris: 21, pemphigus foliaceus: 4) who had received rituximab infusion (rheumatoid arthritis protocol in 21 patients, modified in 4). Oral prednisolone was administered in dosages up to 0.5 mg/kg of body weight and tapered over the next 3-4 months according to the disease activity. However, other immunosuppressive agents such as cyclophosphamide and azathioprine were continued for one year after clinical remission was achieved. Complete remission was observed in 22 (88%) patients. The mean time to disease control and complete remission was 1.10 and 4.36 months, respectively. Four (16%) patients experienced relapse after a mean duration of 11.75 months. The mean total dose of oral steroids administered was equivalent to 3535.64 mg of prednisolone. Exacerbation of disease was noted in two patients after the first dose of rituximab and infectious complications, pneumonia and cellulitis, developed in one patient each. A small sample size, the retrospective nature of the study and unavailability of follow-up anti-desmoglein autoantibodies levels were limitations. Rituximab is an effective agent in the treatment of pemphigus. The use of rituximab enabled use of a lower initial dose of oral prednisolone in pemphigus and hence reduced its total cumulative dose. Severe side effects were rare.

Intermediate doses of rituximab used as adjuvant therapy in refractory pemphigus.

Rituximab, a monoclonal anti-CD20 antibody, has been used with encouraging results in pemphigus. We describe herein refractory cases of pemphigus vulgaris (n = 23) and pemphigus foliaceus (n = 1) treated with rituximab in addition to steroids and immunosuppressants. To assess the response to treatment, the duration of clinical remission, serology of the response and adverse effects of rituximab in pemphigus patients. We recorded observations of 24 patients with pemphigus having either refractory disease in spite of high dose of steroids and immunosuppressants, corticosteroid-dependent disease, strong contraindications to corticosteroids, or severe disease. The patients were treated with infusions of one injection per week for three consecutive weeks of 375 mg of rituximab per m ² of body-surface area. One similar infusion was repeated after 3 months of 3 rd dose. We observed the clinical outcome after 6 months of 3 rd dose of rituximab and looked for complete healing of cutaneous and mucosal lesions (complete remission). After follow-up of 7-24 months, five patients showed only partial improvement while 19 of 24 patients had a complete remission 3 months after rituximab. Of these 19 patients, 12 patients achieved complete remission and are off all systemic therapy, and the rest are continuing with no or low dose of steroids with immunosuppressants. Two patients relapsed after initial improvement; one was given moderate dose of oral steroids and immunosuppressant and the other was given repeat single dose of rituximab to control relapse. Rituximab is able to induce a prolonged clinical remission in pemphigus after a single course of four infusions. The high cost and limited knowledge of long term adverse effects are limitations to the use of this biologic agent.

Clinical experiences of different dosing schedules of rituximab in pemphigus with various disease severities

Rituximab, a monoclonal antibody directed against B lymphocytes, has been found to be a therapeutic agent for severe, refractory autoimmune bullous diseases. However, a dosing schedule or treatment indication of rituximab has not yet been established. We investigated the efficacy of rituximab and different dosing schedules for different disease severities, retrospectively. A total of 23 patients with pemphigus who received rituximab were evaluated by a review of medical records. Group 1 patients (n=10) with severe pemphigus were treated with three or four infusions of rituximab at a dose of 375mg/m(2) at 1-week intervals. Group 2 (n=13) patients with mild to moderate pemphigus were treated with two infusions of rituximab at the same dose. Late end points, occurrence of relapse and adverse events and numbers of B cells were evaluated. The mean follow-up period was 25.6months in group 1 and 17.8months in group 2. In group 1, six patients (60.0%) achieved complete remission (CR), including two patients off therapy (CR OFF) and four patients on therapy (CR ON). The other four patients (40.0%) achieved partial remission on therapy (PR ON). In group 2, nine patients (69.2%) achieved CR (4 CR OFF, 5 CR ON) and four patients (30.8%) achieved PR ON. During the follow-up period, relapse occurred in five patients of group 1 and three patients of group 2. No serious adverse events were observed in any patients. We concluded that rituximab is an effective and safe treatment method not only in severe, recalcitrant pemphigus but also in mild to moderate pemphigus. Low dose of rituximab seemed to be sufficient to treat mild to moderate pemphigus.

Efficacy and safety of rituximab in pemphigus: experience of the German Registry of Autoimmune Diseases

Rituximab has been reported to be effective in various small case series of patients with severe and/or refractory pemphigus. However, no systematic evaluation is available to corroborate this observation. The aim of this study was to systematically determine efficacy and safety of rituximab in treatment-resistant pemphigus. Multicenter retrospective, observational study of 36 patients with severe pemphigus vulgaris (n = 33) and pemphigus foliaceus (n = 3) treated with rituximab before August 31(st) , 2008 and enrolled in a national observational registery between December 2008 and June 2009. Within a mean period of observation of 11 (1-37) months, 21 (58 %) pemphigus patients showed complete, 13 (36 %) partial, and 2 (6 %) no response to rituximab treatment. This correlates with a mean improvement of the visual analog scale for well-being of 34 (20-60) at baseline to 75 (40-95) at the last control visit. In 4 (11 %) patients, severe adverse events were recorded including 1 (3 %) serious infection. Data collected in this systematic registry indicate that rituximab is an effective and relatively safe adjuvant treatment option for refractory pemphigus. To further extend our knowledge on efficacy and safety of this drug, controlled prospective trials are required.

Rituximab Immunotherapy in Pemphigus: Therapeutic Effects Beyond B-Cell Depletion

The anti-CD20 mAb rituximab, first approved for use in B-cell malignancies, is increasingly used to treat a variety of autoimmune diseases. Two studies in this issue investigate the effects of rituximab in pemphigus. Rituximab induces not only a depletion of all B cells and a decline of antidesmoglein autoantibodies but also a decrease in desmoglein-specific T cells. Furthermore, B-cell populations recovered after treatment were modified. These novel aspects may contribute to the clinical responses observed in patients.