Controversies on Rituximab Therapy in Sjögren Syndrome-Associated Lymphoproliferation

Abstract

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms. A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) type and very often located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Rituximab (RTX), a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.

Anti-CD 20 monoclonal antibody (rituximab) treatment for inflammatory ocular diseases

“…Sicca syndrome responded much better in the patient's perspective than in clinical objective evaluation, with about half of the patients reporting an improvement in oral and ocular dryness, while objective tests (Schirmer test) remained unchanged or worsened in all the patients [16,17]. Improvement in submandibular flow rate, dry mouth score, IgM rheumatoid factors (RF), fatigue, and health-related quality of life tests, was also observed in Sjogren's patients after treatment with Rituximab [17].…”

“…Several clinical studies have demonstrated the substantial impact of rituximab for treatment of various systemic autoimmune diseases [1][2][3][4][5][6][7][8][10][11][12][13][14][15][16][17]. Evidence of therapeutic effect is also mounting for numerous autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus (SLE), Wegener's granulomatosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, idiopathic thrombocytopenic purpura, multiple sclerosis and Sjogren's syndrome [4,7,[12][13][14][15].…”

“…All patients were ANA positive and negative for RF and HLA-B27 antigens. The mean age at onset of arthritis was 2.8 ± 2.4 (SD) years (range 1-8), while the mean age at onset of uveitis was 4.1 ± 3.9 (SD) years (range 1-12); the mean ocular disease duration was 16.12 years (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and the mean duration of arthritis was 17.35 years (range [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. In six out of eight patients the ocular involvement was bilateral (total number of treated eyes : 14).…”

Autoimmune Disorders and Lymphomas

“…Single-agent chemotherapy is indicated (alkylating agents; purine analogues; monoclonal antibody rituximab) for multiple extra-nodal disease. The purine analogue cladribine has been associated with a 75% complete remission rate in patients with SS-associated MALT lymphoma (Voulgarelis et al, 2002); while the efficacy of the anti-CD20 monoclonal antibody rituximab is controversial (Pijpe et al, 2005, Quartuccio et al, 2009). Combined chemotherapy ( C H O P -l i k e r e g i m e n s ) s h o u l d b e r e s e r v e d t o p a t i e n t s w i t h h i g h t u m o u r b u r d e n o r aggressive lymphoma.…”

B-cell depletion and primary Sjögren’s syndrome: is there a role for rituximab?

“…Recenti dati mostrano inoltre che la terapia con rituximab nella SS si associa più frequentemente che nell'AR allo sviluppo di HACA i quali possono essere responsabili di reazioni infusionali dopo il secondo o il terzo ciclo di terapia, suggerendo la necessità di una forma umanizzata del farmaco. Sulla base delle nuove conoscenze la futura terapia della SS potrebbe avvalersi dell'utilizzo di farmaci anti-B linfociti al fine di garantire il miglioramento della qualità della vita e la riduzione delle complicanze pur esistendo ancora alcune controversie sulla durata della risposta immunologica e sulla tossicità di tali farmaci (9,10).…”