mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2020-1-85-92mrj-998Research ArticleОБЗОРЫREVIEWSЭффективность ритуксимаба при железистых формах болезни Шёгрена по результатам международных клинических исследованийEfficacy of rituximab for glandular Sjö gren's disease according to international clinical trialsТоргашинаА. В.TorgashinaA. V.

115522, , Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

anna.torgashina@gmail.comФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation2020210320201418592Copyright © Торгашина А.В., 20202020Торгашина А.В.Torgashina A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://mrj.ima-press.net/mrj/article/view/998

Болезнь Шёгрена (БШ) – хроническое аутоиммунное заболевание, характеризующееся лимфоплазмоцитарной инфильтрацией экзокринных желез, ведущей к развитию их деструкции и прогрессирующей функциональной недостаточности. Распространенность БШ составляет около 5%, что делает ее одним из наиболее часто встречающихся аутоиммунных заболеваний. БШ зачастую имеет хроническое, медленно прогрессирующее течение.

В статье обсуждаются результаты международных клинических исследований, посвященных эффективности анти-В-клеточной терапии ритуксимабом (РТМ) при железистых формах БШ. Рассмотрено влияние данной терапии на различные иммунологические, гистологические показатели, субъективные и объективные параметры функции желез и активность заболевания. Обсуждаются возможные причины несоответствия результатов открытых клинических исследований и рандомизированных клинических испытаний, а также предикторы эффективности терапии ритуксимабом.

Установлено, что РТМ при БШ эффективно снижает В-клеточную активность, улучшает морфологическую картину в слюнных железах и некоторые внежелезистые проявления заболевания, уменьшает сухость и слабость. Отмечается большой потенциал анти-В-клеточных препаратов в терапии БШ. 

Sjögren's disease (SD) is a chronic autoimmune disease characterized by lymphoplasmacytic infiltration of the exocrine glands, leading to the development of their destruction and progressive functional failure. The prevalence of SD is about 5%, which makes it one of the most common autoimmune diseases. SD often has a chronic, slowly progressing course.

The paper discusses the results of international clinical trials of the efficiency of anti-B-cell therapy with rituximab (RTM) for glandular SD. It considers the impact of this therapy on various immunological, histological indicators, subjective and objective parameters of glandular function, and disease activity. Possible reasons for the discrepancy between the results of open-label clinical trials and randomized clinical trials, as well as predictors for the efficiency of RTM therapy are discussed.

It has been found that RTM used to treat SD effectively reduces B-cell activity, improves the morphological pattern in the salivary glands and some extraglandular manifestations of the disease, and diminishes dryness and weakness. Anti-B-cell drugs have a great potential to treat SD. 

сиалоаденитритуксимабанти-В-клеточная терапияболезнь Шёгренасухой синдромsialadenitisrituximabanti-B-cell therapySjögren's diseasedry syndromeReferencesСафонова ТН, Васильев ВИ, Лихванцева ВГ. Синдром Шегрена: Руководство для врачей. Москва: Издательство Московского университета; 2013.Safonova TN, Vasil'ev VI, Likhvantseva VG. Sindrom Shegrena: Rukovodstvo dlya vrachei [Sjö gren's syndrome: A guide for doctors]. Moscow: Izdatel'stvo Moskovskogo universiteta; 2013 (In Russ.).Patel R, Shahane A. The epidemiology of Sjö gren's syndrome. Clin Epidemiol. 2014;6:247-55. doi: 10.2147/CLEP.S47399Patel R, Shahane A. The epidemiology of Sjö gren's syndrome. Clin Epidemiol. 2014;6:247-55. doi: 10.2147/CLEP.S47399Brito-Zeron P, Baldini C, Bootsma H, et al. Sjö gren syndrome. Nat Rev Dis Primer. 2016;2:16047. doi: 10.1038/nrdp.2016.47Brito-Zeron P, Baldini C, Bootsma H, et al. Sjö gren syndrome. Nat Rev Dis Primer. 2016;2:16047. doi: 10.1038/nrdp.2016.47Solans-Laque R, Lopez-Hernandez A, Angel Bosch-Gil J, et al. Risk, predictors, and clinical characteristics of lymphoma development in primary Sjö gren's syndrome. Semin Arthritis Rheum. 2011;41:415-23. doi: 10.1016/j.semarthrit.2011.04.006Solans-Laque R, Lopez-Hernandez A, Angel Bosch-Gil J, et al. Risk, predictors, and clinical characteristics of lymphoma development in primary Sjö gren's syndrome. Semin Arthritis Rheum. 2011;41:415-23. doi: 10.1016/j.semarthrit.2011.04.006Логвиненко ОА, Васильев ВИ. Неходжкинские лимфомы при ревматических заболеваниях. Научно-практическая ревматология. 2011;49(5):71-82. doi: 10.14412/1995-4484-2011-1464.Logvinenko OA, Vasil'ev VI. Non-Hodgkin's lymphoma in rheumatic diseases. NauchnoPrakticheskaya Revmatologiya = Rheumatology Science and Practice. 2011; 49(5):71-82. doi: 10.14412/1995-4484-2011-1464 (In Russ.).Gottenberg JE, Ravaud P, Puchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjö gren syndrome: the JOQUER randomized clinical trial. JAMA. 2014;312(3):249-58. doi: 10.1001/jama.2014.7682Gottenberg JE, Ravaud P, Puchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjö gren syndrome: the JOQUER randomized clinical trial. JAMA. 2014;312(3):249-58. doi: 10.1001/jama.2014.7682Brito-Zeron P, Ramos-Casals M. Advances in the understanding and treatment of systemic complications in Sjö gren's syndrome. Curr Opin Rheumatol. 2014 Sep;26(5):520-7. doi: 10.1097/BOR.0000000000000096Brito-Zeron P, Ramos-Casals M. Advances in the understanding and treatment of systemic complications in Sjö gren's syndrome. Curr Opin Rheumatol. 2014 Sep;26(5):520-7. doi: 10.1097/BOR.0000000000000096Kroese FG, Abdulahad WH, Haacke E, et al. B-cell hyperactivity in primary Sjö gren's syndrome. Expert Rev Clin Immunol. 2014;10:483-99. doi: 10.1586/1744666X.2014.891439Kroese FG, Abdulahad WH, Haacke E, et al. B-cell hyperactivity in primary Sjö gren's syndrome. Expert Rev Clin Immunol. 2014;10:483-99. doi: 10.1586/1744666X.2014.891439Shaw T, Quan J, Totoritis MC. B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Ann Rheum Dis. 2003;62(2):ii55-9. doi: 10.1136/ard.62.suppl_2.ii55Shaw T, Quan J, Totoritis MC. B cell therapy for rheumatoid arthritis: the rituximab (anti-CD20) experience. Ann Rheum Dis. 2003;62(2):ii55-9. doi: 10.1136/ard.62.suppl_2.ii55Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjö gren's syndrome: an open-label phase II study. Arthritis Rheum. 2005;52: 2740-50. doi: 10.1002/art.21260Pijpe J, van Imhoff GW, Spijkervet FK, et al. Rituximab treatment in patients with primary Sjö gren's syndrome: an open-label phase II study. Arthritis Rheum. 2005;52: 2740-50. doi: 10.1002/art.21260Pijpe J, Meijer JM, Bootsma H, et al. Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjö gren's syndrome. Arthritis Rheum. 2009;60:3251-6. doi: 10.1002/art.24903Pijpe J, Meijer JM, Bootsma H, et al. Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjö gren's syndrome. Arthritis Rheum. 2009;60:3251-6. doi: 10.1002/art.24903Devauchelle-Pensec V, Pennec Y, Morvan J, et al. Improvement of Sjö gren's Syndrome after two infusions of rituximab (Anti-CD20). Arthritis Rheum. 2007;57: 310-7. doi: 10.1002/art.22536Devauchelle-Pensec V, Pennec Y, Morvan J, et al. Improvement of Sjö gren's Syndrome after two infusions of rituximab (Anti-CD20). Arthritis Rheum. 2007;57: 310-7. doi: 10.1002/art.22536Devauchelle-Pensec V, Morvan J, Rat AC, et al. Effects of rituximab therapy on quality of life in patients with primary Sjö gren's syndrome. Clin Exp Rheumatol. 2011;29(1):6-12.Devauchelle-Pensec V, Morvan J, Rat AC, et al. Effects of rituximab therapy on quality of life in patients with primary Sjö gren's syndrome. Clin Exp Rheumatol. 2011;29(1):6-12.Gottenberg JE, Cinquetti G, Larroche C, et al. Efficacy of rituximab in systemic manifestations of primary Sjö gren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis. 2013;72(6): 1026-31. doi: 10.1136/annrheumdis-2012-202293Gottenberg JE, Cinquetti G, Larroche C, et al. Efficacy of rituximab in systemic manifestations of primary Sjö gren's syndrome: results in 78 patients of the AutoImmune and Rituximab registry. Ann Rheum Dis. 2013;72(6): 1026-31. doi: 10.1136/annrheumdis-2012-202293St Clair EW, Levesque MC, Prak ET, et al. Rituximab therapy for primary Sjö gren's syndrome: an open-label clinical trial and mechanistic analysis. Arthritis Rheum. 2013; 65:1097-106. doi: 10.1002/art.37850St Clair EW, Levesque MC, Prak ET, et al. Rituximab therapy for primary Sjö gren's syndrome: an open-label clinical trial and mechanistic analysis. Arthritis Rheum. 2013; 65:1097-106. doi: 10.1002/art.37850Carubbi F, Cipriani P, Marrelli A, et al. Efficacy and safety of rituximab treatment in early primary Sjö gren's syndrome: a prospective, multi-center, follow-up study. Arthritis Res Ther. 2013 Oct 30;15(5):R172. doi: 10.1186/ar4359Carubbi F, Cipriani P, Marrelli A, et al. Efficacy and safety of rituximab treatment in early primary Sjö gren's syndrome: a prospective, multi-center, follow-up study. Arthritis Res Ther. 2013 Oct 30;15(5):R172. doi: 10.1186/ar4359Dass S, Bowman SJ, Vital EM, et al. Reduction of fatigue in Sjö gren syndrome with rituximab: results of a randomized, double-blind, placebo controlled pilot study. Ann Rheum Dis. 2008;67:1541-4. doi: 10.1136/ard.2007.083865Dass S, Bowman SJ, Vital EM, et al. Reduction of fatigue in Sjö gren syndrome with rituximab: results of a randomized, double-blind, placebo controlled pilot study. Ann Rheum Dis. 2008;67:1541-4. doi: 10.1136/ard.2007.083865Meijer J, Meiners P, Vissink A, et al. Effective rituximab treatment in primary Sjö gren's syndrome: A randomised, doubleblind, placebo-controlled trial. Arthritis Rheum. 2010;62:960-8. doi: 10.1002/art.27314Meijer J, Meiners P, Vissink A, et al. Effective rituximab treatment in primary Sjö gren's syndrome: A randomised, doubleblind, placebo-controlled trial. Arthritis Rheum. 2010;62:960-8. doi: 10.1002/art.27314Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Treatment of primary Sjö gren syndrome with rituximab: A randomized trial. Ann Intern Med. 2014;160(4): 233-42. doi: 10.7326/M13-1085Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Treatment of primary Sjö gren syndrome with rituximab: A randomized trial. Ann Intern Med. 2014;160(4): 233-42. doi: 10.7326/M13-1085Bowman SJ, Everett CC, O'Dwyer JL, et al. Randomized controlled trial of rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjö gren's syndrome. Arthritis Rheum. 2017; 69(7):1440-50. doi: 10.1002/art.40093Bowman SJ, Everett CC, O'Dwyer JL, et al. Randomized controlled trial of rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjö gren's syndrome. Arthritis Rheum. 2017; 69(7):1440-50. doi: 10.1002/art.40093Meiners PM, Arends S, Meijer JM, et al. Efficacy of retreatment with rituximab in patients with primary Sjö gren's syndrome. Clin Exp Rheumatol. 2015;33:443-4.Meiners PM, Arends S, Meijer JM, et al. Efficacy of retreatment with rituximab in patients with primary Sjö gren's syndrome. Clin Exp Rheumatol. 2015;33:443-4.Meiners PM, Arends S, Brouwer E, et al. Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjögren's syndrome treated with rituximab. Ann Rheum Dis. 2012;71:1297-302. doi: 10.1136/annrheumdis-2011-200460Meiners PM, Arends S, Brouwer E, et al. Responsiveness of disease activity indices ESSPRI and ESSDAI in patients with primary Sjögren's syndrome treated with rituximab. Ann Rheum Dis. 2012;71:1297-302. doi: 10.1136/annrheumdis-2011-200460Seror R, Sordet C, Guillevin G, et al. Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjö gren's syndrome. Ann Rheum Dis. 2007;66:351-7. doi: 10.1136/ard.2006.057919Seror R, Sordet C, Guillevin G, et al. Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjö gren's syndrome. Ann Rheum Dis. 2007;66:351-7. doi: 10.1136/ard.2006.057919Nocturne G, Virone A, Ng WF, et al. Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sjö gren's syndrome. Arthritis Rheum. 2016 Apr;68(4):977-85. doi: 10.1002/art.39518Nocturne G, Virone A, Ng WF, et al. Rheumatoid factor and disease activity are independent predictors of lymphoma in primary Sjö gren's syndrome. Arthritis Rheum. 2016 Apr;68(4):977-85. doi: 10.1002/art.39518Verstappen GM, Kroese FG, Meiners PM, et al. B cell depletion therapy normalizes circulating follicular Th cells in primary Sjö gren syndrome. J Rheumatol. 2017 Jan;44(1):49-58. doi: 10.3899/jrheum.160313Verstappen GM, Kroese FG, Meiners PM, et al. B cell depletion therapy normalizes circulating follicular Th cells in primary Sjö gren syndrome. J Rheumatol. 2017 Jan;44(1):49-58. doi: 10.3899/jrheum.160313Scofield RH, Farris AD, Horsfall AC. Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. Arthritis Rheum. 1999 Feb;42(2): 199-209. doi: 10.1002/1529-0131(199902)42: 23.0.CO;2-1Scofield RH, Farris AD, Horsfall AC. Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. Arthritis Rheum. 1999 Feb;42(2): 199-209. doi: 10.1002/1529-0131(199902)42: 23.0.CO;2-1Verstappen GM, van Nimwegen JF, Vissink A, et al. The value of rituximab treatment in primary Sjö gren's syndrome. Clin Immunol. 2017 Sep;182:62-71. doi: 10.1016/j.clim.2017.05.002Verstappen GM, van Nimwegen JF, Vissink A, et al. The value of rituximab treatment in primary Sjö gren's syndrome. Clin Immunol. 2017 Sep;182:62-71. doi: 10.1016/j.clim.2017.05.002Gottenberg GE, Seror R, Miceli-Richard C, et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjö gren's syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One. 2013 May 24;8(5):e59868. doi: 10.1371/journal.pone.0059868Gottenberg GE, Seror R, Miceli-Richard C, et al. Serum levels of beta2-microglobulin and free light chains of immunoglobulins are associated with systemic disease activity in primary Sjö gren's syndrome. Data at enrollment in the prospective ASSESS cohort. PLoS One. 2013 May 24;8(5):e59868. doi: 10.1371/journal.pone.0059868Kormelink TG, Tekstra J, Thurlings RM, et al. Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis. 2010;69:2137-44. doi: 10.1136/ard.2009.126441Kormelink TG, Tekstra J, Thurlings RM, et al. Decrease in immunoglobulin free light chains in patients with rheumatoid arthritis upon rituximab (anti-CD20) treatment correlates with decrease in disease activity. Ann Rheum Dis. 2010;69:2137-44. doi: 10.1136/ard.2009.126441Pollard RP, Abdulahad WH, Bootsma H, et al. Predominantly proinflammatory cytokines decrease after B cell depletion therapy in patients with primary Sjö gren's syndrome. Ann Rheum Dis. 2013;72:2048-50. doi: 10.1136/annrheumdis-2013-203447Pollard RP, Abdulahad WH, Bootsma H, et al. Predominantly proinflammatory cytokines decrease after B cell depletion therapy in patients with primary Sjö gren's syndrome. Ann Rheum Dis. 2013;72:2048-50. doi: 10.1136/annrheumdis-2013-203447Pollard RP, Abdulahad WH, Vissink A, et al. Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in patients with primary Sjö gren's syndrome: data from a placebo-controlled clinical trial. Ann Rheum Dis. 2013 Jan;72(1):146-8. doi: 10.1136/annrheumdis-2012-202071Pollard RP, Abdulahad WH, Vissink A, et al. Serum levels of BAFF, but not APRIL, are increased after rituximab treatment in patients with primary Sjö gren's syndrome: data from a placebo-controlled clinical trial. Ann Rheum Dis. 2013 Jan;72(1):146-8. doi: 10.1136/annrheumdis-2012-202071Ehrenstein MR, Wing C. The BAFFling effects of rituximab in lupus: danger ahead? Nat Rev Rheumatol. 2016;12:367-72. doi: 10.1038/nrrheum.2016.18Ehrenstein MR, Wing C. The BAFFling effects of rituximab in lupus: danger ahead? Nat Rev Rheumatol. 2016;12:367-72. doi: 10.1038/nrrheum.2016.18Delli K, Haacke EA, Kroese FG, et al. Towards personalised treatment in primary Sjö gren's syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis. 2016 Nov; 75(11):1933-8. doi: 10.1136/annrheumdis2015-208304Delli K, Haacke EA, Kroese FG, et al. Towards personalised treatment in primary Sjö gren's syndrome: baseline parotid histopathology predicts responsiveness to rituximab treatment. Ann Rheum Dis. 2016 Nov; 75(11):1933-8. doi: 10.1136/annrheumdis2015-208304Haacke EA, Vegt B, Meiners PM, et al. Abatacept treatment of patients with primary Sjö gren's syndrome results in a decrease of germinal centres in salivary gland tissue. Clin Exp Rheumatol. 2017 Mar-Apr;35(2):317-20.Haacke EA, Vegt B, Meiners PM, et al. Abatacept treatment of patients with primary Sjö gren's syndrome results in a decrease of germinal centres in salivary gland tissue. Clin Exp Rheumatol. 2017 Mar-Apr;35(2):317-20.Haacke BH, Kroese FGM, Kluin P, et al. Salivary Gland FcRL4+ B-Cells Are a Potential Source of Progenitor Cells for MALT Lymphoma in Primary Sjö gren's Syndrome – ACR Meeting Abstracts. Arthritis Rheum. 2015;Suppl 10:67.Haacke BH, Kroese FGM, Kluin P, et al. Salivary Gland FcRL4+ B-Cells Are a Potential Source of Progenitor Cells for MALT Lymphoma in Primary Sjö gren's Syndrome – ACR Meeting Abstracts. Arthritis Rheum. 2015;Suppl 10:67.Hamza N, Bootsma H, Yuvaraj S, et al. Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjö gren's syndrome after B cell depletion therapy. Ann Rheum Dis. 2012;71: 1881-7. doi: 10.1136/annrheumdis-2011-201189Hamza N, Bootsma H, Yuvaraj S, et al. Persistence of immunoglobulin-producing cells in parotid salivary glands of patients with primary Sjö gren's syndrome after B cell depletion therapy. Ann Rheum Dis. 2012;71: 1881-7. doi: 10.1136/annrheumdis-2011-201189Thurlings RM, Vos K, Wijbrandts CA, et al. Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response. Ann Rheum Dis. 2008;67:917-25. doi: 10.1136/ard.2007.080960Thurlings RM, Vos K, Wijbrandts CA, et al. Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response. Ann Rheum Dis. 2008;67:917-25. doi: 10.1136/ard.2007.080960Burlage FR, Pijpe J, Coppes RP, et al. Variability of flow rate when collecting stimulated human parotid saliva. Eur J Oral Sci. 2005;113:386-90. doi: 10.1111/j.1600-0722.2005.00241.xBurlage FR, Pijpe J, Coppes RP, et al. Variability of flow rate when collecting stimulated human parotid saliva. Eur J Oral Sci. 2005;113:386-90. doi: 10.1111/j.1600-0722.2005.00241.xJousse-Joulin S, Devauchelle-Pensec V, Morvan J, et al. Ultrasound assessment of salivary glands in patients with primary Sjö gren's syndrome treated with rituximab: Quantitative and Doppler waveform analysis. Biologics. 2007 Sep;1(3):311-9.Jousse-Joulin S, Devauchelle-Pensec V, Morvan J, et al. Ultrasound assessment of salivary glands in patients with primary Sjö gren's syndrome treated with rituximab: Quantitative and Doppler waveform analysis. Biologics. 2007 Sep;1(3):311-9.Jousse-Joulin S, Devauchelle-Pensec V, Cornec D. Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjö gren's Syndrome. Arthritis Rheum. 2015 Jun;67(6):1623-8. doi: 10.1002/art.39088Jousse-Joulin S, Devauchelle-Pensec V, Cornec D. Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjö gren's Syndrome. Arthritis Rheum. 2015 Jun;67(6):1623-8. doi: 10.1002/art.39088Nichols KK, Mitchell GL, Zadnik K. The repeatability of clinical measurements of dry eye. Cornea. 2004;23:272-85. doi: 10.1097/00003226-200404000-00010Nichols KK, Mitchell GL, Zadnik K. The repeatability of clinical measurements of dry eye. Cornea. 2004;23:272-85. doi: 10.1097/00003226-200404000-00010Rose-Nussbaumer J, Lietman TM, Shiboski CH, et al. Inter-grader Agreement of the Ocular Staining Score in the Sjö gren's International Clinical Collaborative Alliance (SICCA) Registry. Am J Ophthalmol. 2015; 160:1150-3. doi: 10.1016/j.ajo.2015.08.021Rose-Nussbaumer J, Lietman TM, Shiboski CH, et al. Inter-grader Agreement of the Ocular Staining Score in the Sjö gren's International Clinical Collaborative Alliance (SICCA) Registry. Am J Ophthalmol. 2015; 160:1150-3. doi: 10.1016/j.ajo.2015.08.021Cornec D, Devauchelle-Pensec V, Mariette XS, et al. Development of the Sjö gren's Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy. Rheumatology. 2015;54:1699-708. doi: 10.1093/rheumatology/kev114Cornec D, Devauchelle-Pensec V, Mariette XS, et al. Development of the Sjö gren's Syndrome Responder Index, a data-driven composite endpoint for assessing treatment efficacy. Rheumatology. 2015;54:1699-708. doi: 10.1093/rheumatology/kev114Benucci M, Manfredi M, Puttini PS, et al. Predictive factors of response to rituximab therapy in rheumatoid arthritis: What do we know today? Autoimmun Rev. 2010; 9:801-3. doi: 10.1016/j.autrev.2010.07.006Benucci M, Manfredi M, Puttini PS, et al. Predictive factors of response to rituximab therapy in rheumatoid arthritis: What do we know today? Autoimmun Rev. 2010; 9:801-3. doi: 10.1016/j.autrev.2010.07.006Anolik HN, Campbell D, Felgar RE, et al. The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. 2003;48:455-9. doi: 10.1002/art.10764Anolik HN, Campbell D, Felgar RE, et al. The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Arthritis Rheum. 2003;48:455-9. doi: 10.1002/art.10764Cornec D, Costa S, DevauchellePensec V, et al. Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjö gren's syndrome. J Autoimmun. 2016; 67:102-10. doi: 10.1016/j.jaut.2015.11.002Cornec D, Costa S, DevauchellePensec V, et al. Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjö gren's syndrome. J Autoimmun. 2016; 67:102-10. doi: 10.1016/j.jaut.2015.11.002Delli K, Haacke EA, Kroese FG, et al. In primary Sjö gren's syndrome high absolute numbers and proportions of B cells in parotid glands predict responsiveness to rituximab as defined by ESSDAI, but not by SSRI. Ann Rheum Dis. 2016 Jun;75(6):e34. doi: 10.1136/annrheumdis-2016-209317Delli K, Haacke EA, Kroese FG, et al. In primary Sjö gren's syndrome high absolute numbers and proportions of B cells in parotid glands predict responsiveness to rituximab as defined by ESSDAI, but not by SSRI. Ann Rheum Dis. 2016 Jun;75(6):e34. doi: 10.1136/annrheumdis-2016-209317Letaief H, Lukas C, Barnetche T, et al. Efficacy and safety of biological DMARDs modulating B cells in primary Sjö gren's syndrome: Systematic review and meta-analysis. Joint Bone Spine. 2018 Jan;85(1):15-22. doi: 10.1016/j.jbspin.2017.06.004Letaief H, Lukas C, Barnetche T, et al. Efficacy and safety of biological DMARDs modulating B cells in primary Sjö gren's syndrome: Systematic review and meta-analysis. Joint Bone Spine. 2018 Jan;85(1):15-22. doi: 10.1016/j.jbspin.2017.06.004Aure MH, Arany S, Ovitt CE. Salivary Glands: Stem Cells, Self-duplication, or Both? J Dent Res. 2015;94(11):1502-7. doi: 10.1177/0022034515599770Aure MH, Arany S, Ovitt CE. Salivary Glands: Stem Cells, Self-duplication, or Both? J Dent Res. 2015;94(11):1502-7. doi: 10.1177/0022034515599770Tarn JR, Howard-Tripp N, Lendrem DW, et al. Symptom-based stratification of patients with primary Sjö gren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019;1:e85-94.Tarn JR, Howard-Tripp N, Lendrem DW, et al. Symptom-based stratification of patients with primary Sjö gren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019;1:e85-94.Seror R, Bootsma H, Saraux A, et al. Defining disease activity states and clinically meaningful improvement in primary Sjö gren's syndrome with EULAR primary Sjö gren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis. 2016 Feb;75(2): 382-9.Seror R, Bootsma H, Saraux A, et al. Defining disease activity states and clinically meaningful improvement in primary Sjö gren's syndrome with EULAR primary Sjö gren's syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis. 2016 Feb;75(2): 382-9.Bezzina OM, Gallagher P, Mitchell S, et al. Subjective and Objective Measures of Dryness Symptoms in Primary Sjö gren's Syndrome – Capturing the discrepancy. Arthritis Care Res (Hoboken). 2017 Nov; 69(11):1714-23. doi: 10.1002/acr.23165Bezzina OM, Gallagher P, Mitchell S, et al. Subjective and Objective Measures of Dryness Symptoms in Primary Sjö gren's Syndrome – Capturing the discrepancy. Arthritis Care Res (Hoboken). 2017 Nov; 69(11):1714-23. doi: 10.1002/acr.23165Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjö gren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjö gren's syndrome. Ann Rheum Dis. 2010;69:1103-9. doi: 10.1136/ard.2009.110619Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjö gren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjö gren's syndrome. Ann Rheum Dis. 2010;69:1103-9. doi: 10.1136/ard.2009.110619

The authors declare that there are no conflicts of interest present.