The evolving role of rituximab in the treatment of pemphigus vulgaris: a comprehensive state-of-the-art review

References

• Bystryn J-C, Rudolph JL. Pemphigus. Lancet. 2005;366(9479):61–73.
   PubMed Web of Science ®Google Scholar
• Hertl M, Jedlickova H, Karpati S, et al. Pemphigus. S2 guideline for diagnosis and treatment - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2015;29(3):405–414.
   PubMed Web of Science ®Google Scholar
• Bystryn JC, Steinman NM. The adjuvant therapy of pemphigus. An update. Arch Dermatol. 1996;132(2):203–212.
   PubMedGoogle Scholar
• Kridin K, Zelber-Sagi S, Bergman R. Pemphigus vulgaris and pemphigus foliaceus: differences in epidemiology and mortality. Acta Derm Venereol. 2017;97(9):1095–1099.
   PubMed Web of Science ®Google Scholar
• Kridin K, Sagi S, Bergman R. Mortality and cause of death in israeli patients with pemphigus. Acta Derm Venereol. 2017;97(5):607–611.
   Web of Science ®Google Scholar
• Murrell DF, Dick S, Ahmed AR, et al. Consensus statement on definitions of disease, end points, and therapeutic response for pemphigus. J Am Acad Dermatol. 2008;58(6):1043–1046.
   PubMed Web of Science ®Google Scholar
• Murrell DF, Peña S, Joly P, et al. Diagnosis and management of pemphigus: recommendations by an international panel of experts. J Am Acad Dermatol. 2018;82(3):575–585.e1.
   PubMed Web of Science ®Google Scholar
• Martin LK, Werth VP, Villaneuva EV, et al. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol. 2011;64(5):903–908.
   PubMed Web of Science ®Google Scholar
• Harman KE, Brown D, Exton LS, et al. British Association of Dermatologists’ guidelines for the management of pemphigus vulgaris 2017. Br J Dermatol. 2017;177(5):1170–1201.
   PubMed Web of Science ®Google Scholar
• Sebaratnam DF, Hanna AM, Chee S-N, et al. Charles Qian Wang, Belinda Welsh, Tamar Nijsten, Dédée F Murrell. Development of a quality-of-life instrument for autoimmune bullous disease: the autoimmune bullous disease quality of life questionnaire. JAMA Dermatol. 2013 Oct;149(10):1186–1191.
   PubMed Web of Science ®Google Scholar
• Hébert V, Boulard C, Houivet E, et al. Large international validation of absis and pdai pemphigus severity scores. J Invest Dermatol. 2019 Jan;139(1):31–37.
   PubMed Web of Science ®Google Scholar
• Bezombes C, Fournié JJ, Laurent G. Direct effect of rituximab in B-cell-derived lymphoid neoplasias: mechanism, regulation, and perspectives. Mol Cancer Res. 2011;9(11):1435–1442.
   PubMed Web of Science ®Google Scholar
• Seyfizadeh N, Seyfizadeh N, Hasenkamp J, et al. A molecular perspective on rituximab: a monoclonal antibody for B cell non Hodgkin lymphoma and other affections. Crit Rev Oncol Hematol. 2016;97:275–290.
   PubMed Web of Science ®Google Scholar
• Golay J, Introna M. Mechanism of action of therapeutic monoclonal antibodies: promises and pitfalls of in vitro and in vivo assays. Arch Biochem Biophys. 2012;526(2):146–153.
   PubMed Web of Science ®Google Scholar
• Meurer M. Immunosuppressive therapy for autoimmune bullous diseases. Clin Dermatol. 2012;30(1):78–83.
   PubMed Web of Science ®Google Scholar
• Eming R, Nagel A, Wolff-Franke S, et al. Rituximab exerts a dual effect in pemphigus vulgaris. J Invest Dermatol. 2008;128(12):2850–2858.
   PubMed Web of Science ®Google Scholar
• Zambruno G, Borradori L. Rituximab immunotherapy in pemphigus: therapeutic effects beyond B-cell depletion. J Invest Dermatol. 2008;128(12):2745–2747.
   PubMed Web of Science ®Google Scholar
• Leshem YA, David M, Hodak E, et al. A prospective study on clinical response and cell-mediated immunity of pemphigus patients treated with rituximab. Arch Dermatol Res. 2014;306(1):67–74.
   PubMed Web of Science ®Google Scholar
• Pollmann R, Schmidt T, Eming R, et al. Pemphigus: a comprehensive review on pathogenesis, clinical presentation and novel therapeutic approaches. Clin Rev Allergy Immunol. 2018. DOI:10.1007/s12016-017-8662-z
   PubMed Web of Science ®Google Scholar
• Kridin K, Ahn C, Huang WC, et al. Treatment update of autoimmune blistering diseases. Dermatol Clin. 2019;37(2):215–228.
   PubMed Web of Science ®Google Scholar
• Kridin K. Emerging treatment options for the management of pemphigus vulgaris. Ther Clin Risk Manag. 2018;14:757–778. [Volume].
   PubMed Web of Science ®Google Scholar
• Colliou N, Picard D, Caillot F, et al. Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response. Sci Transl Med. 2013;5(175):5.
   Web of Science ®Google Scholar
• Kim J, Daniel BS, Werth VP, et al. The treatment of pemphigus vulgaris and pemphigus foliaceus. In: Murrell DF, editor. Blistering diseases: clinical features, pathogenesis, treatment. Berlin, Heidelberg: Springer Berlin Heidelberg; 2015. p. 533–541.
   Google Scholar
• Lo SA, Puca RV, Ruocco V, et al. Adjuvant drugs in autoimmune bullous diseases, efficacy versus safety: facts and controversies. Clin Dermatol. 2010;28(3):337–343.
   PubMed Web of Science ®Google Scholar
• Schmidt E, Bröcker EB, Goebeler M. Rituximab in treatment-resistant autoimmune blistering skin disorders. Clin Rev Allergy Immunol. 2008;34(1):56–64.
   PubMed Web of Science ®Google Scholar
• Hertl M, Zillikens D, Borradori L, et al. Recommendations for the use of rituximab (anti-CD20 antibody) in the treatment of autoimmune bullous skin diseases. J Dtsch Dermatol Ges. 2008;6(5):366–373.
   PubMed Web of Science ®Google Scholar
• Karmacharya P, Poudel DR, Pathak R, et al. Rituximab-induced serum sickness: a systematic review. Semin Arthritis Rheum. 2015;45(3):334–340.
   PubMed Web of Science ®Google Scholar
• Didona D, Maglie R, Eming R, et al. Pemphigus: current and future therapeutic strategies. Front Immunol. 2019. DOI:10.3389/fimmu.2019.01418
   Web of Science ®Google Scholar
• Feldman RJ. Paradoxical worsening of pemphigus vulgaris following rituximab therapy. Br J Dermatol. 2015;173(3):858–859.
   Web of Science ®Google Scholar
• Kusumoto S, Arcaini L, Hong X, et al. Risk of HBV reactivation in patients with B-cell lymphomas receiving obinutuzumab or rituximab immunochemotherapy. Blood. 2019 Jan 10;133(2):137–146.
   PubMed Web of Science ®Google Scholar
• Leung C, Tsoi E, Burns G, et al. An argument for the universal prophylaxis of hepatitis B infection in patients receiving rituximab: a 7-year institutional experience of hepatitis screening. Oncologist. 2011;16(5):579–584.
   PubMed Web of Science ®Google Scholar
• Spina M, Tirelli U. Rituximab for HIV-associated lymphoma: weighing the benefits and risks. Curr Opin Oncol. 2005 Sep;17(5):462–465.
   PubMed Web of Science ®Google Scholar
• Papp KA, Haraoui B, Kumar D, et al. Vaccination guidelines for patients with immune-mediated disorders taking immunosuppressive therapies: executive summary. J Rheumatol. 2019 Jul;46(7):751–754.
   PubMed Web of Science ®Google Scholar
• Cho A, Bradley B, Kauffman R, et al. Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab. JCI Insight. 2017;2(12). DOI:10.1172/jci.insight.93222
   Web of Science ®Google Scholar
• Kasperkiewicz M, Eming R, Behzad M, et al. Efficacy and safety of rituximab in pemphigus: experience of the German Registry of Autoimmune Diseases. J Dtsch Dermatol Ges. 2012;10(10):727–731.
   PubMed Web of Science ®Google Scholar
• Williams M, Khalid T, Hughes S, et al. Rituximab-induced Cytokine storm in the absence of overt lymphoproliferative disease. J Pediatr Hematol Oncol. 2016;38(1):e29-e31.
   PubMed Web of Science ®Google Scholar
• Chiu HY, Chang CY, Hsiao CH, et al. Concurrent cytomegalovirus and herpes simplex virus infection in pemphigus vulgaris treated with rituximab and prednisolone. Acta Derm Venereol. 2013;93(2):200–201.
   PubMed Web of Science ®Google Scholar
• Maglie R, Hertl M. Assessment of serious infections in pemphigus and pemphigoid by a national registry. J Eur Acad Dermatol Venereol. 2018;32(10):1623–1624.
   PubMed Web of Science ®Google Scholar
• Barreto JN, Ice LL, Thompson CA, et al. Low incidence of pneumocystis pneumonia utilizing PCR-based diagnosis in patients with B-cell lymphoma receiving rituximab-containing combination chemotherapy. Am J Hematol. 2016 Nov;91(11):1113–1117.
   PubMed Web of Science ®Google Scholar
• Amber KT, Lamberts A, Solimani F, et al. Determining the incidence of pneumocystis pneumonia in patients with autoimmune blistering diseases not receiving routine prophylaxis. JAMA Dermatol. 2017 Nov 1;153(11):1137–1141.
   PubMed Web of Science ®Google Scholar
• Wei K-C, Chen W, Tang P-L, et al. Pneumocystis jirovecii pneumonia infection in pemphigus patients treated with rituximab: an observational nationwide epidemiological study in Taiwan. Eur J Dermatol. 2018 Oct 1;28(5):713–715.
   PubMed Web of Science ®Google Scholar
• Chen DM, Odueyungbo A, Csinady E, et al. Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect. Br J Dermatol. 2020 May;182(5):1111–1119.
   PubMed Web of Science ®Google Scholar
• Zakka LR, Shetty SS, Ahmed AR. Rituximab in the treatment of pemphigus vulgaris. Dermatol Ther (Heidelb). 2012;2(1):1–13.
   PubMedGoogle Scholar
• Ahmed AR, Spigelman Z, Cavacini LA, et al. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Engl J Med. 2006;355:1772–1779.
   PubMed Web of Science ®Google Scholar
• Joly P, Mouquet H, Roujeau J-C, et al. A single cycle of rituximab for the treatment of severe pemphigus. N Engl J Med. 2007;357(6):545–552.
   PubMed Web of Science ®Google Scholar
• Cianchini G, Lupi F, Masini C, et al. Therapy with rituximab for autoimmune pemphigus: results from a single-center observational study on 42 cases with long-term follow-up. J Am Acad Dermatol. 2012;67(4):617–622.
   PubMed Web of Science ®Google Scholar
• Joly P, Maho-Vaillant M, Prost-Squarcioni C, et al. First-line rituximab combined with short-term prednisone versus prednisone alone for the treatment of pemphigus (Ritux 3): a prospective, multicentre, parallel-group, open-label randomised trial. Lancet. 2017;389(10083):2031–2040.
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Rituximab Versus Mycophenolate Mofetil (MMF) in Participants With Pemphigus Vulgaris (PV) - Full Text View - ClinicalTrials.gov [WWW Document]. URL https://clinicaltrials.gov/ct2/show/study/NCT02383589?cond=pemphigus&draw=2&rank=11&view=results [accessed on 2018 Feb 23
   Google Scholar
• ClinicalTrials.gov. Comparative Study of Rituximab Versus Combination of Rituximab and Intravenous Cyclophosphamide in Severe Pemphigus - Full Text View - ClinicalTrials.gov [WWW Document]. URL https://clinicaltrials.gov/ct2/show/NCT01974518?cond=pemphigus&draw=5&rank=3 [accessed on 2018 Feb 24
   Google Scholar
• Schmidt E, Goebeler M, Zillikens D. Rituximab in severe pemphigus. Ann N Y Acad Sci. 2009;1173(1):683–691.
   PubMedGoogle Scholar
• Saleh MA. A prospective study comparing patients with early and late relapsing pemphigus treated with rituximab. J Am Acad Dermatol. 2018;79(1):97–103.
   PubMed Web of Science ®Google Scholar
• Wang HH, Liu CW, Li YC, et al. Efficacy of rituximab for pemphigus: a systematic review and meta-analysis of different regimens. Acta Derm Venereol. 2015;95(8):928–932.
   PubMed Web of Science ®Google Scholar
• Ahmed AR, Shetty S. A comprehensive analysis of treatment outcomes in patients with pemphigus vulgaris treated with rituximab. Autoimmun Rev. 2015;14(4):323–331.
   PubMed Web of Science ®Google Scholar
• Kushner CJ, Wang S, Tovanabutra N, et al. Factors associated with complete remission after rituximab therapy for pemphigus. JAMA Dermatol. 2019 Oct 23;155(12):1404–1409.
   PubMed Web of Science ®Google Scholar
• Ahmed AR, Kaveri S, Spigelman Z. Longterm remissions on recalcitrant pemphigus vulgaris. N Engl J Med. 2015;373(27):2693–2694.
   PubMed Web of Science ®Google Scholar
• Ahmed AR, Kaveri S. Reversing autoimmunity: combination of rituximab and intravenous immunoglobulin. Front Immunol. 2018;9:1189.
   PubMed Web of Science ®Google Scholar
• Joly P, Horwath B, Patsatsi Α, et al. Updated S2K guidelines on the management of pemphigus vulgaris and foliaceus initiated by the European academy of dermatology and venereology (EADV). J Eur Acad Dermatol Venereol. 2020 Aug 24;34(9):1900–1913.
   Web of Science ®Google Scholar
• Ingen-Housz-Oro S, Valeyrie-Allanore L, Cosnes A, et al. First-line treatment of pemphigus vulgaris with a combination of rituximab and high-potency topical corticosteroids. JAMA Dermatol. 2015;151(2):200.
   Web of Science ®Google Scholar
• Ahmed AR, Nguyen T, Kaveri S, et al. First line treatment of pemphigus vulgaris with a novel protocol in patients with contraindications to systemic corticosteroids and immunosuppressive agents: preliminary retrospective study with a seven year follow-up. Int Immunopharmacol. 2016;34:25–31.
   PubMed Web of Science ®Google Scholar
• Gregoriou S, Efthymiou O, Stefanaki C, et al. Management of pemphigus vulgaris: challenges and solutions. Clin Cosmet Investig Dermatol. 2015;8:521–527.
   PubMed Web of Science ®Google Scholar
• Kanwar AJ, Vinay K, Sawatkar GU, et al. Clinical and immunological outcomes of high- and low-dose rituximab treatments in patients with pemphigus: A randomized, comparative, observer-blinded study. Br J Dermatol. 2014;170(6):1341–1349.
   PubMed Web of Science ®Google Scholar
• Ng CM, Bruno R, Combs D, et al. Population pharmacokinetics of rituximab (anti-CD20 monoclonal antibody) in rheumatoid arthritis patients during a phase II clinical trial. J Clin Pharmacol. 2005;45(7):792–801.
   PubMed Web of Science ®Google Scholar
• Kim JH, Kim YH, Kim MR, et al. Clinical efficacy of different doses of rituximab in the treatment of pemphigus: a retrospective study of 27 patients. Br J Dermatol. 2011;165(3):646–651.
   PubMed Web of Science ®Google Scholar
• Heelan K, Al-Mohammedi F, Smith MJ, et al. Durable remission of pemphigus with a fixed-dose rituximab protocol. JAMA Dermatol. 2014;150(7):703.
   PubMed Web of Science ®Google Scholar
• Russo I, Miotto S, Saponeri A, et al. Ultra-low dose rituximab for refractory pemghigus vulgaris: a pilot study. Expert Opin Biol Ther. 2020 Jun;20(6):673–678.
   PubMed Web of Science ®Google Scholar
• Schoergenhofer C, Schwameis M, Firbas C, et al. Single, very low rituximab doses in healthy volunteers - a pilot and a randomized trial: implications for dosing and biosimilarity testing. Sci Rep. 2018 Jan 9;8(1):124.
   PubMedGoogle Scholar
• Gregoriou S, Giatrakou S, Theodoropoulos K, et al. Pilot study of 19 patients with severe pemphigus: prophylactic treatment with rituximab does not appear to be beneficial. Dermatology. 2014;228(2):158–165.
   PubMed Web of Science ®Google Scholar
• Manz RA, Arce S, Cassese G, et al. Humoral immunity and long-lived plasma cells. Curr Opin Immunol. 2002;14(4):517–521.
   PubMed Web of Science ®Google Scholar
• Albers LN, Liu Y, Bo N, et al. Developing biomarkers for predicting clinical relapse in pemphigus patients treated with rituximab. J Am Acad Dermatol. 2017;77(6):1074–1082.
   PubMed Web of Science ®Google Scholar
• Tavakolpour S, Mahmoudi HR, Balighi K, et al. Sixteen-year history of rituximab therapy for 1085 pemphigus vulgaris patients: a systematic review. Int Immunopharmacol. 2018;54:131–138.
   PubMed Web of Science ®Google Scholar
• Feldman RJ, Christen WG, Ahmed AR. Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy. Br J Dermatol. 2012;166(3):511–517.
   Web of Science ®Google Scholar
• Hammers CM, Chen J, Lin C, et al. Persistence of anti-desmoglein 3 IgG(+) B-cell clones in pemphigus patients over years. J Invest Dermatol. 2015 Mar;135(3):742–749.
   PubMed Web of Science ®Google Scholar
• Hamza N, Bootsma H, Yuvaraj S, et al. Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjögren’s syndrome after B cell depletion therapy. Ann Rheum Dis. 2012 Nov;71(11):1881–1887.
   PubMed Web of Science ®Google Scholar
• Mouquet H, Musette P, Gougeon ML, et al. B-cell depletion immunotherapy in pemphigus: effects on cellular and humoral immune responses. J Invest Dermatol. 2008;128(12):2859–2869.
   PubMed Web of Science ®Google Scholar
• Behzad M, Möbs C, Kneisel A, et al. Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris. Br J Dermatol. 2012;166(4):844–852.
   PubMed Web of Science ®Google Scholar
• Amber KT, Valdebran M, Grando SA. Non-desmoglein antibodies in patients with pemphigus vulgaris. Front Immunol. 2018;9. DOI:10.3389/fimmu.2018.01190.
   PubMed Web of Science ®Google Scholar
• Ahmed AR, Carrozzo M, Caux F, et al. Monopathogenic vs multipathogenic explanations of pemphigus pathophysiology. Exp Dermatol. 2016;25(11):839–846.
   PubMed Web of Science ®Google Scholar
• Cho SI, Kim JW, Lim JS, et al. Mucosal involvement is a risk factor for poor clinical outcomes and relapse in patients with pemphigus treated with rituximab. Dermatol Ther. 2019;32(2):e12814.
   Web of Science ®Google Scholar
• Kneiber D, Kowalski E, Kridin K, et al. Pemphigus subtype: A confounder in determining the association of oral involvement with post‐rituximab relapses. Dermatol Ther. 2019;32(3):e12918.
   PubMed Web of Science ®Google Scholar
• Ffrooz A, Tehranchia-nia, Ahmed AR, et al. Benefits and risks of intralesional corticosteroid injection in the treatment of dermatological diseases. Clinical and Experimental Dermatology. 1995;20(5):363–370.
   PubMed Web of Science ®Google Scholar
• Nguyen T, Ahmed AR. Pemphigus vulgaris localized to the tongue. J Dermatol Case Rep. 2014;2:55–57.
   Google Scholar
• Yuan H, Zhou S, Liu Z, et al. Pivotal role of lesional and perilesional t/b lymphocytes in pemphigus pathogenesis. J Invest Dermatol. 2017;137(11):2362–2370.
   PubMed Web of Science ®Google Scholar
• Zhou S, Liu Z, Yuan H, et al. Autoreactive b cell differentiation in diffuse ectopic lymphoid-like structures of inflamed pemphigus lesions. J Invest Dermatol. 2008;128:2859069.
   Google Scholar
• Gupta A, Sharma YK, Bhawalkar JS, et al. Intralesional rituximab salvages refractory scalp lesions in a case of pemphigus vulgaris. Dermatol Ther. 2020;33(1):e13154.
   Web of Science ®Google Scholar
• Vinay K, Kanwar AJ, Mittal A, et al. Intralesional rituximab in the treatment of refractory oral pemphigus vulgaris. JAMA Dermatol. 2015;151(8):878–882.
   PubMed Web of Science ®Google Scholar
• Iraji F, Danesh F, Faghihi G, et al. Comparison between the efficacy of intralesional rituximab versus intraregional triamcinolone in the treatment of refractory pemphigus vulgaris lesions: a randomized clinical trial. Int Immunopharmacol. 2019;73:94–97.
   PubMed Web of Science ®Google Scholar
• Bhol K, Natarajan K, Nagarwalla N, et al. Correlation of peptide specificity and IgG subclass with pathogenic and nonpathogenic autoantibodies in pemphigus vulgaris: a model for autoimmunity. Proc Natl Acad Sci USA. 1995;92:5239–5243.
   PubMed Web of Science ®Google Scholar
• Tony H-P, Burmester G, Schulze-Koops H, et al. Ina Kötter, & GRAID investigators. Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID). Arthritis Res Ther. 2011 May 13;13(3):R75.
   PubMed Web of Science ®Google Scholar
• Naseer SY, Seiffert-Sinha K, Sinha AA. Detailed profiling of anti-desmoglein autoantibodies identifies anti-Dsg1 reactivity as a key driver of disease activity and clinical expression in pemphigus vulgaris. Autoimmunity. 2015 Jun;48(4):231–241.
   PubMed Web of Science ®Google Scholar
• Daneshpazhooh M, Kamyab K, Kalantari M-S, et al. Comparison of desmoglein 1 and 3 enzyme-linked immunosorbent assay and direct immunofluorescence for evaluation of immunological remission in pemphigus vulgaris. Clin Exp Dermatol. 2014 Jan;39(1):41–47.
   PubMed Web of Science ®Google Scholar
• Yanovski R, McLeod M, Ahmed AR. Treatment of pemphigus vulgaris: part 2 - emerging therapies. Expert Rev Clin Immunol. 2019;15(10):1061–1071.
   PubMed Web of Science ®Google Scholar