389
Views
5
CrossRef citations to date
0
Altmetric
Review

An update of targeted therapeutic options for primary Sjögren syndrome: current status and future development

, , , ORCID Icon &
Pages 2359-2371 | Received 05 Feb 2021, Accepted 30 Jun 2021, Published online: 29 Jul 2021

References

  • Brito-Zerón P, Baldini C, Bootsma H, et al. Sjögren syndrome. Nat Rev Dis Primers. 2016;2:16047.
  • Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, et al. Primary Sjogren syndrome. BMJ. 2012;344:e3821.
  • Mariette X, Criswell LA. Primary Sjogren’s Syndrome. N Engl J Med. 2018;378:931–939.
  • Flores-Chávez A, Kostov B, Solans R, et al. Severe, life-threatening phenotype of primary Sjögren’s syndrome: clinical characterisation and outcomes in 1580 patients (GEAS-SS Registry). Clin Exp Rheumatol. 2018;36(Suppl 112):121–129.
  • Brito-Zeron P, Retamozo S, Phenotyping Sjogren’s R-CM. syndrome: towards a personalised management of the disease. Clin Exp Rheumatol. 2018;36(Suppl 112):198–209.
  • Seror R, Ravaud P, Bowman SJ, et al. EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis. 2010;69:1103–1109.
  • Seror R, Bowman SJ, Brito-Zeron P, et al. EULAR Sjögren’s syndrome disease activity index (ESSDAI): a user guide. RMD Open. 2015;1:e000022.
  • Seror R, Bootsma H, Saraux A, et al. Defining disease activity states and clinically meaningful improvement in primary Sjogren’s syndrome with EULAR primary Sjogren’s syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis. 2016;75:382–389.
  • Ramos-Casals M, Tzioufas AG, Stone JH, et al. Treatment of primary Sjogren syndrome: a systematic review. JAMA. 2010;304:452–460.
  • Elliott MJ, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum. 2008;58:S92–S10.
  • Brito-Zerón P, Siso-Almirall A, Bove A, et al. Primary Sjogren syndrome: an update on current pharmacotherapy options and future directions. Expert Opin Pharmacother. 2013;14:279–289.
  • Mavragani CP, Moutsopoulos HM. Sjögren’s syndrome: old and new therapeutic targets. J Autoimmun. 2020;110:102364.
  • Mariette X, Ravaud P, Steinfeld S, et al. Inefficacy of infliximab in primary Sjogren’s syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjogren’s Syndrome (TRIPSS). Arthritis Rheum. 2004;50:1270–1276.
  • Roescher N, Tak PP, Illei GG. Cytokines in Sjogren’s syndrome: potential therapeutic targets. Ann Rheum Dis. 2010;69:945–948.
  • Fasano S, Isenberg DA. Present and novel biologic drugs in primary Sjögren’s syndrome. Clin Exp Rheumatol. 2019;37(Suppl 118):167–174.
  • Ramos-Casals M, Brito-Zerón P, Bombardieri S, et al. EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies. Ann Rheum Dis. 2020;79:3–18.
  • Gottenberg JE, Ravaud P, Puéchal X, et al. Effects of hydroxychloroquine on symptomatic improvement in primary Sjögren syndrome: the JOQUER randomized clinical trial. JAMA. 2014;312:249–258.
  • Brito-Zerón P, Retamozo S, Kostov B, et al. Efficacy and safety of topical and systemic medications: a systematic literature review informing the EULAR recommendations for the management of Sjögren’s syndrome. RMD Open. 2019;5:e001064.
  • Graves J, Vinayagasundaram U, Mowry EM, et al. Effects of rituximab on lymphocytes in multiple sclerosis and neuromyelitis optica. Mult Scler Relat Disord. 2014;3:244–252.
  • Pijpe J, Meijer JM, Bootsma H, et al. Clinical and histologic evidence of salivary gland restoration supports the efficacy of rituximab treatment in Sjögren’s syndrome. Arthritis Rheum. 2009;60:3251–3256.
  • Alunno A, Carubbi F, Bistoni O, et al. Interleukin (IL)-17-producing pathogenic T lymphocytes co-express CD20 and are depleted by rituximab in primary Sjogren’s syndrome: a pilot study. Clin Exp Immunol. 2016;184:284–292.
  • Ciccia F, Guggino G, Rizzo A, et al. Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjogren’s syndrome. Rheumatology (Oxford). 2014;53:1313–1320.
  • Jiang B, Li T, Guo L, et al. Efficacy and Safety of Rituximab in Systemic Lupus Erythematosus and Sjogren Syndrome Patients With Refractory Thrombocytopenia: a Retrospective Study of 21 Cases. J Clin Rheumatol. 2015;21:244–250.
  • Devauchelle-Pensec V, Mariette X, Jousse-Joulin S, et al. Treatment of primary Sjogren syndrome with rituximab: a randomized trial. Ann Intern Med. 2014;160:233–242.
  • Fisher BA, Everett CC, Rout J, et al. Effect of rituximab on a salivary gland ultrasound score in primary Sjogren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy. Ann Rheum Dis. 2018;77:412–416.
  • FB Do V S, Gjm P, BNG A, et al. Rituximab Effectiveness and Safety for Treating Primary Sjogren’s Syndrome (pSS): systematic Review and Meta-Analysis. PLoS One. 2016;11:e0150749.
  • Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, et al. Topical and systemic medications for the treatment of primary Sjögren’s syndrome. Nat Rev Rheumatol. 2012;8:399–411.
  • Pavlych V, Di Muzio C, Alunno A, et al. Comparison of Rituximab Originator With CT-P10 Biosimilar in Patients With Primary Sjögren’s Syndrome: a Retrospective Analysis in a Real-Life Setting. Front Med (Lausanne). 2020;7:534.
  • Goede V, Fischer K, Engelke A, et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia. 2015;29:1602–1604.
  • Hammett EK, Fernandez-Carbonell C, Crayne C, et al. Adolescent Sjogren’s syndrome presenting as psychosis: a case series. Pediatr Rheumatol Online J. 2020;18:15.
  • Combier A, Nocturne G, Henry J, et al. Immunization to rituximab is more frequent in systemic autoimmune diseases than in rheumatoid arthritis: ofatumumab as alternative therapy. Rheumatology (Oxford). 2020;59:1347–1354.
  • clinicaltrials.gov . [cited 2021 Jan 25]. Available online: https://www.clinicaltrials.gov/.
  • Steinfeld SD, Tant L, Burmester GR, et al. Epratuzumab (humanised anti-CD22 antibody) in primary Sjögren’s syndrome: an open-label phase I/II study. Arthritis Res Ther. 2006;8:R129.
  • Gottenberg JE, Dörner T, Bootsma H, et al. Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythematosus Patients With Associated Sjögren’s Syndrome: post Hoc Analyses From the EMBODY Trials. Arthritis Rheumatol. 2018;70:763–773.
  • Pontarini E, Verstappen GM, Grigoriadou S, et al. Blocking T cell co-stimulation in primary Sjögren’s syndrome: rationale, clinical efficacy and modulation of peripheral and salivary gland biomarkers. Clin Exp Rheumatol. 2020;38(Suppl 126):222–227.
  • Adler S, Korner M, Forger F, et al. Evaluation of histologic, serologic, and clinical changes in response to abatacept treatment of primary Sjogren’s syndrome: a pilot study. Arthritis Care Res (Hoboken). 2013;65:1862–1868.
  • Meiners PM, Vissink A, Kroese FGM, et al. Abatacept treatment reduces disease activity in early primary Sjögren’s syndrome (open-label proof of concept ASAP study). Ann Rheum Dis. 2014;73:1393–1396.
  • Tsuboi H, Matsumoto I, Hagiwara S, et al. Efficacy and safety of abatacept for patients with Sjögren’s syndrome associated with rheumatoid arthritis: rheumatoid arthritis with orencia trial toward Sjögren’s syndrome Endocrinopathy (ROSE) trial-an open-label, one-year, prospective study-Interim analysis of 32 patients for 24 weeks. Mod Rheumatol. 2015;25:187–193.
  • Machado AC, Dos Santos LC, Fidelix T, et al. Effectiveness and safety of abatacept for the treatment of patients with primary Sjögren’s syndrome. Clin Rheumatol. 2020;39:243–248.
  • Baer AN, Gottenberg JE, St Clair EW, et al. Efficacy and safety of abatacept in active primary Sjögren’s syndrome: results of a phase III, randomised, placebo-controlled trial. Ann Rheum Dis. 2020;80:339–348.
  • Schroder PM, Schmitz R, Fitch ZW, et al. Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model. Kidney Int. 2021;99:161–172.
  • Espié P, He Y, Koo P, et al. First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody. Am J Transplant. 2020;20:463–473.
  • Fisher B, Szántó A, Ng WF, et al. Subcutaneous dosing of the novel anti-CD40 antibody iscalimab achieves target drug exposure and clinical efficacy in primary Sjögren’s syndrome; results of a phase iia randomised open label two arm parallel group trial. Ann Rheum Dis. 2019;78:760– 761.
  • Marinelli O, Nabissi M, Morelli MB, et al. ICOS-L as a Potential Therapeutic Target for Cancer Immunotherapy. Curr Protein Pept Sci. 2018;19:1107–1113.
  • Mariette X, Bombardieri M, Alevizos I, et al. A Phase 2a Study of MEDI5872 (AMG557), a Fully Human Anti-ICOS Ligand Monoclonal Antibody in Patients with Primary Sjögren’s Syndrome. Arthritis Rheumatol. 2019;71(suppl):10.
  • Dillon S, Evans L, Lewis K, et al. ALPN-101, a First-in-Class Dual ICOS/CD28 Antagonist, Suppresses Key Effector Mechanisms Associated with Sjögren’s Syndrome. Arthritis Rheumatol. 2019;71(suppl):10.
  • Stohl W. Therapeutic targeting of the BAFF/APRIL axis in systemic lupus erythematosus. Expert Opin Ther Targets. 2014;18:473–489.
  • The R-CM. B-lymphocyte stimulator connection in Sjogren’s syndrome. Rheumatology (Oxford). 2013;52:223–225.
  • Alunno A, Carubbi F, Bistoni O, et al. T Regulatory and T Helper 17 Cells in Primary Sjogren’s Syndrome: facts and Perspectives. Mediators Inflamm. 2015;2015:243723.
  • Quartuccio L, Salvin S, Fabris M, et al. BLyS upregulation in Sjogren’s syndrome associated with lymphoproliferative disorders, higher ESSDAI score and B-cell clonal expansion in the salivary glands. Rheumatology (Oxford). 2013;52:276–281.
  • Hf D, Bjurman C, Rehnberg E, et al. Interleukin 6 and its soluble receptor in a central role at the neuroimmunoendocrine interface in Sjogren syndrome: an explanatory interventional study. Ann Rheum Dis. 2009;68:285–286.
  • Tzioufas AG, Kapsogeorgou EK, Moutsopoulos HM. Pathogenesis of Sjögren’s syndrome: what we know and what we should learn. J Autoimmun. 2012;39:4–8.
  • Mariette X, Seror R, Quartuccio L, et al. Efficacy and safety of belimumab in primary Sjogren’s syndrome: results of the BELISS open-label phase II study. Ann Rheum Dis. 2015;74:526–531.
  • Pontarini E, Fabris M, Quartuccio L, et al. Treatment with belimumab restores B cell subsets and their expression of B cell activating factor receptor in patients with primary Sjogren’s syndrome. Rheumatology (Oxford). 2015;54:1429–1434.
  • De Vita S, Quartuccio L, Seror R, et al. Efficacy and safety of belimumab given for 12 months in primary Sjogren’s syndrome: the BELISS open-label phase II study. Rheumatology (Oxford). 2015;54:2249–2256.
  • Quartuccio L, Salvin S, Corazza L, et al. Efficacy of belimumab and targeting of rheumatoid factor-positive B-cell expansion in Sjogren’s syndrome: follow-up after the end of the phase II open-label BELISS study. Clin Exp Rheumatol. 2016;34:311–314.
  • Stohl W. Inhibition of B cell activating factor (BAFF) in the management of systemic lupus erythematosus (SLE). Expert Rev Clin Immunol. 2017;13:623–633.
  • Dörner T, Posch MG, Li Y, et al. Treatment of primary Sjögren’s syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Ann Rheum Dis. 2019;78:641–647.
  • Diekhoff T, Fischer T, Schefer Q, et al. Ianalumab (VAY736) in primary Sjögren’s syndrome: assessing disease activity using multi-modal ultrasound. Clin Exp Rheumatol. 2020;38(Suppl 126):228–236.
  • Gatumu MK, Skarstein K, Papandile A, et al. Blockade of lymphotoxin-beta receptor signaling reduces aspects of Sjogren’s syndrome in salivary glands of non-obese diabetic mice. Arthritis Res Ther. 2009;11:R24.
  • Fava RA, Browning JL, Gatumu M, et al. LTBR-pathway in Sjogren’s syndrome: CXCL13 levels and B-cell-enriched ectopic lymphoid aggregates in NOD mouse lacrimal glands are dependent on LTBR. Adv Exp Med Biol. 2011;691:383–390.
  • St.Clair EW, Baer AN, Noaiseh G, et al. The Clinical Efficacy and Safety of Baminercept, a Lymphotoxin-Beta Receptor Fusion Protein, in Primary Sjögren’s Syndrome: results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial. Arthritis Rheumatol. 2015;67(suppl):10.
  • Retamozo S, Flores-Chavez A, Consuegra-Fernández M, et al. Cytokines as therapeutic targets in primary Sjögren syndrome. Pharmacol Ther. 2018;184:81–97.
  • Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011;365:2067–2077.
  • Humrich JY, Riemekasten G. Restoring regulation - IL-2 therapy in systemic lupus erythematosus. Expert Rev Clin Immunol. 2016;12:1153–1160.
  • Ballesteros-Tato A, Papillion A. Mechanisms of action of low-dose IL-2 restoration therapies in SLE. Curr Opin Immunol. 2019;61:39–45.
  • Justet A, Ottaviani S, Dieude P, et al. Tocilizumab for refractory organising pneumonia associated with Sjogren’s disease. BMJ Case Rep. 2015;2015:bcr2014209076.
  • Komai T, Shoda H, Yamaguchi K, et al. Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: a case report. Mod Rheumatol. 2016;26:294–296.
  • Marino A, Narula S, Lerman MA. First Pediatric Patient With Neuromyelitis Optica and Sjögren Syndrome Successfully Treated With Tocilizumab. Pediatr Neurol. 2017;73:e5–e6.
  • Ishikawa Y, Hattori K, Ishikawa J, et al. Refractory Sjögren’s syndrome myelopathy successfully treated with subcutaneous tocilizumab: a case report. Medicine (Baltimore). 2019;98:e16285.
  • Felten R, Devauchelle-Pensec V, Seror R, et al. Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial. Ann Rheum Dis. 2020 annrheumdis-2020-218467. http://DOI:101136annrheumdis-2020.218467.
  • Lee BH, Carcamo WC, Chiorini JA, et al. Gene therapy using IL-27 ameliorates Sjogren’s syndrome-like autoimmune exocrinopathy. Arthritis Res Ther. 2012;14:R172.
  • Norheim KB, Harboe E, Gøransson LG, et al. Interleukin-1 inhibition and fatigue in primary Sjogren's syndrome - a double blind, randomised clinical trial. PLoS One. 2012;7:e30123.
  • Low HZ, Witte T. Aspects of innate immunity in Sjogren’s syndrome. Arthritis Res Ther. 2011;13:218.
  • Mathian A, Hie M, Cohen-Aubart F, et al. Targeting interferons in systemic lupus erythematosus: current and future prospects. Drugs. 2015;75:835–846.
  • Posada J, Valadkhan S, Burge D, et al. Improvement of Severe Fatigue Following Nuclease Therapy in Patients With Primary Sjögren’s Syndrome: a Randomized Clinical Trial. Arthritis Rheumatol. 2021;73:143–150.
  • Bhullar KS, Lagaron NO, McGowan EM, et al. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol Cancer. 2018;17:48.
  • Zarrin AA, Bao K, Lupardus P, et al. Kinase inhibition in autoimmunity and inflammation. Nat Rev Drug Discov. 2021;20:39–63.
  • Roskoski RJ. Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol Res. 2019;144:19–50.
  • Seebacher NA, Stacy AE, Porter GM, et al. Clinical development of targeted and immune based anti-cancer therapies. J Exp Clin Cancer Res. 2019;38:156.
  • Bousoik E, Montazeri Aliabadi H. “Do We Know Jack” About JAK? A Closer Look at JAK/STAT Signaling Pathway. Front Oncol. 2018;8:287.
  • Barrera MJ, Aguilera S, Castro I, et al. Tofacitinib counteracts IL-6 overexpression induced by deficient autophagy: implications in Sjögren’s syndrome. Rheumatology (Oxford). 2021;60:1951–1962.
  • Aota K, Yamanoi T, Kani K, et al. Inhibition of JAK-STAT Signaling by Baricitinib Reduces Interferon-γ-Induced CXCL10 Production in Human Salivary Gland Ductal Cells. Inflammation. 2021;44:206–216.
  • Kannan N, Taylor SS, Zhai Y, et al. Structural and functional diversity of the microbial kinome. PLoS Biol. 2007;5:e17.
  • Fabbro D, Cowan-Jacob SW, Moebitz H. Ten things you should know about protein kinases: IUPHAR Review 14. Br J Pharmacol. 2015;172:2675–2700.
  • Lien EC, Dibble CC, Toker A. PI3K signaling in cancer: beyond AKT. Curr Opin Cell Biol. 2017;45:62–71.
  • Alzahrani AS. PI3K/Akt/mTOR inhibitors in cancer: at the bench and bedside. Semin Cancer Biol. 2019;59:125–132.
  • Juarez M, Diaz N, Johnston GI, et al. A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren’s syndrome. Rheumatology (Oxford). 2021;60:1364–1375.
  • Dörner T, Zeher M, Laessing U, et al. randomised, double-blind study to assess the safety, tolerability and preliminary efficacy of leniolisib (CDZ173) in patients with primary Sjögren’s syndrome. Ann Rheum Dis. 2018;77:174.
  • Dhillon S. Tirabrutinib: first Approval. Drugs. 2020;80:835–840.
  • Gabizon R, London NA. Fast and Clean BTK Inhibitor. J Med Chem. 2020;63:5100–5510.
  • Liu D, Mamorska-Dyga A. Syk inhibitors in clinical development for hematological malignancies. J Hematol Oncol. 2017;10:145.
  • Blomgren P, Chandrasekhar J, Di Paolo JA, et al. Discovery of Lanraplenib (GS-9876): a Once-Daily Spleen Tyrosine Kinase Inhibitor for Autoimmune Diseases. ACS Med Chem Lett. 2020;11:506–513.
  • Jousse-Joulin S, Gatineau F, Baldini C, et al. Weight of salivary gland ultrasonography compared to other items of the 2016 ACR/EULAR classification criteria for Primary Sjögren’s syndrome. J Intern Med. 2020;287:180–188.
  • Gheitasi H, Kostov B, Solans R, et al. How are we treating our systemic patients with primary Sjögren syndrome? Analysis of 1120 patients. Int Immunopharmacol. 2015;27:194–199.
  • Vollert J, Cook NR, Kaptchuk TJ, et al. Assessment of Placebo Response in Objective and Subjective Outcome Measures in Rheumatoid Arthritis Clinical Trials. JAMA Network Open. 2020;3:e2013196.
  • Jiang W, Zhang L, Zhao Y, et al. The efficacy and mechanism for action of iguratimod in primary Sjögren’s syndrome patients. Int Ophthalmol. 2020;40:3059–3065.
  • Chen H, Qi X, Li Y, et al. Iguratimod treatment reduces disease activity in early primary Sjögren’s syndrome: an open-label pilot study. Mod Rheumatol. 2021;31:394–398.
  • Shao Q, Wang S, Jiang H, et al. Efficacy and safety of iguratimod on patients with primary Sjögren’s syndrome: a randomized, placebo-controlled clinical trial. Scand J Rheumatol. 2021;50:143–152.
  • Gandolfo S, De Vita S. Double anti-B cell and anti-BAFF targeting for the treatment of primary Sjögren’s syndrome. Clin Exp Rheumatol. 2019;37(Suppl 118):199–208.
  • Cornec D, Costa S, Devauchelle-Pensec V, et al. Blood and salivary-gland BAFF-driven B-cell hyperactivity is associated to rituximab inefficacy in primary Sjogren’s syndrome. J Autoimmun. 2016;67:102–110.
  • Chevalier K, Belkhir R, Seror R, et al. Efficacy of a sequential treatment by anti-CD 20 monoclonal antibody and belimumab in type II cryoglobulinaemia associated with primary Sjögren syndrome refractory to rituximab alone. Ann Rheum Dis. 2020;79:1257–1259.
  • Saadoun D, Ghembaza A, Riviere S, et al. Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: a pilot study. J Autoimmun. 2021;116:102577.
  • Benschop RJ, Chow CK, Tian Y, et al. Development of tibulizumab, a tetravalent bispecific antibody targeting BAFF and IL-17A for the treatment of autoimmune disease. MAbs. 2019;11:1175–1190.
  • Boutros C, Tarhini A, Routier E, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol. 2016;13:473–486.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.