Abstract
Rituximab (RTX) is a chimeric anti-CD20 antibody, approved for rheumatoid arthritis (RA) patients who failed anti-Tumor Necrosis Factor therapy. It has been used occasionally for life-threatening autoimmune diseases (AID). We report our center experience in the use of RTX in life-threatening complications or refractory AID. Clinical charts of patients treated with RTX at our center were reviewed, cases treated for life-threatening complications or refractory AID were analyzed. Acute damage to vital organs such as lung, heart, kidney, nervous system with severe functional impairment were defined as life-threatening complications; treatment failure with high-dose corticosteroids, cyclophosphamide, IVIG, plasmapheresis was defined as refractory autoimmune disease. During the years 2003–2009, 117 patients were treated with RTX, most of them for RA. Nine patients (6 females, mean age 51.5 years, mean disease duration 6.3 years) answered the criteria. The indications were as follows: pulmonary hemorrhage (1 patient with cryoglobulinemic vasculitis, 1 with systemic sclerosis, 1 with ANCA-associated vasculitis), catastrophic anti-phospholipid syndrome (2 SLE patients), non-bacterial endocarditis and pulmonary hypertension (1 patient with mixed connective tissue disease), vasculitis and feet necrosis (1 patient with systemic lupus erythematosus), severe lupus demyelinative neuropathy and acute renal failure (1patient), and severe rheumatoid lung disease with recurrent empyema and pneumothorax (1patient). B cell depletion was achieved in all patients. The median time since starting of complications to RTX administration was 3 weeks (range 2–15 weeks). Complete remission (suppression of the hazardous situation and return to previous stable state) was seen in 7 out of 9 patients. Partial remission (significant improvement) was achieved in the remained. The median time to response was 3 weeks (range 1–8 weeks), mean follow-up 47.2 months (range 6–60 months). A rapid tapering off of steroids was achieved in all patients. Two patients relapsed and were successfully retreated with RTX: the patient with severe RA lung relapsed after 3 years, one of the patients with ANCA-associated pulmonary alveolar hemorrhage relapsed after 10 months. There were no side effects during RTX infusion. Two episodes of serious infections were registered: fatal Gram-negative sepsis 6 months after RTX treatment, and septic discitis 4 months after receiving RTX. RTX serves as a safe, efficient, and prompt rescue therapy in certain life-threatening conditions and resistant to aggressive immunosuppression AID. RTX when administrated at an earlier stage, prevented irreversible vital organ damage, and allowed rapid steroid tapering off in already severe immunodepressed patients.
Similar content being viewed by others
References
McDonald V, Leandro M (2009) Rituximab in non-haematological disorders of adults and its mode of action. BJH 146:233–246
Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R et al (1994) Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–445
Pescovitz MD (2006) Rituximab, an anti-CD20 monoclonal antibody: history and mechanism of action. Am J Transplant 6:859–866
Guillevin L, Durand-Gasselin B, Cevallos R et al (1999) Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients. Arthritis Rheum 42(3):421–430
Lauque D, Cadranel J, Lazor R et al (2000) Microscopic polyangiitis with alveolar hemorrhage. A study of 29 cases and review of the literature. Groupe d’Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires (GERM“O”P). Medicine (Baltimore) 79(4):222–233
Schwarz MI, Brown KK (2000) Small vessel vasculitis of the lung. Thorax 55(6):502–510
Lara AR, Schwarz MI (2010) Diffuse alveolar hemorrhage. Chest 137(5):1164–1171
Pottier V, Pierrot M, Subra JF, Mercat A, Kouatchet A, Parrot A, Augusto JF. Successful rituximab therapy in a lupus patient with diffuse alveolar haemorrhage. Lupus. 2011 May; 20(6):656–659. Epub 2011 Feb 18
Narshi CB, Haider S, Ford CM, Isenberg DA, Giles IP (2010) Rituximab as early therapy for pulmonary haemorrhage in systemic lupus erythematosus. Rheumatology (Oxford) 49(2):392–394
Pinto LF, Candia L, Garcia P, Marín JI, Pachón I, Espinoza LR, Marquez J (2009) Effective treatment of refractory pulmonary hemorrhage with monoclonal anti-CD20 antibody (rituximab). Respiration 78(1):106–109
Nellessen CM, Pöge U, Brensing KA, Sauerbruch T, Klehr HU, Rabe C (2008) Diffuse alveolar haemorrhage in a systemic lupus erythematosus patient successfully treated with rituximab: a case report. Nephrol Dial Transplant 23(1):385–386
Arad U, Balbir-Gurman A, Doenyas-Barak K, Amit-Vazina M, Caspi D, Elkayam O (2011) Anti-neutrophil antibody associated vasculitis in systemic sclerosis. Semin Arthritis Rheum 41(2):223–229
Elazary AS, Klahr P, Hershko A, Dranitzki Z, Rubinow A, Naparstek Y (2012) Rituximab induces resolution of recurrent diffuse alveolar hemorrhage in a patient with primary antiphospholipid antibody syndrome. Lupus 21(4):438–440
Rubenstein E, Arkfeld DG, Metyas S, Shinada S, Ehresmann S, Liebman HA (2006) Rituximab treatment for resistant antiphospholipid syndrome. J Rheumatol 33:355–357
Manner H, Jung B, Tonassi L et al (2008) Successful treatment of catastrophic antiphospholipid antibody syndrome (CAPS) associated with splenic marginal-zone lymphoma with low-molecular weight heparin, rituximab and bendamustine. Am J Med Sci 335:394–397
van Wissen S, Bastiaansen BMJ, Stroobants AK et al (2008) Catastrophic antiphospholipid syndrome mimicking a malignant pancreatic tumour—a case report. Lupus 17:586–590
Asherson RA, Espinosa G, Menahem S et al (2008) Relapsing catastrophic antiphospholipid syndrome: report of three cases. Semin Arthritis Rheum 37:377–382
Nageswara Rao AA, Arteaga GM, Reed AM, Gloor JM, Rodriguez V (2009) Rituximab for successful management of probable pediatric catastrophic antiphospholipid syndrome. Pediatr Blood Cancer 52:536–538
Jamoussi SK, Zaghdoudi I, Ben Dhaou B et al (2009) Catastrophic antiphospholipid syndrome and rituximab: a new report. Tunis Med 87:699–702
Iglesias-Jiménez E, Camacho-Lovillo M, Falcón-Neyra D, Lirola-Cruz J, Neth O (2010) Infant with probable catastrophic antiphospholipid syndrome successfully managed with rituximab. Pediatrics 125:e1523–e1528
Espinosa G, Berman H, Cervera R (2011) Management of refractory cases of catastrophic antiphospholipid syndrome. Autoimmun Rev 10(11):664–668
Hennigan S, Channick RN, Silverman GJ (2008) Rituximab treatment of pulmonary arterial hypertension associated with systemic lupus erythematosus: a case report. Lupus 17(8):754–756
Lui NL, Thumboo J, Fong KY (2009) A case of refractory vasculitic ulcers in a systemic lupus erythematosus patient responding to rituximab and hyperbaric oxygen therapy. Int J Rheum Dis 12(4):366–369
Ramos-Casals M, García-Hernández FJ, de Ramón E, Callejas JL, Martínez-Berriotxoa A, Pallarés L, Caminal-Montero L, Selva-O’Callaghan A, Oristrell J, Hidalgo C, Pérez-Alvarez R, Micó ML, Medrano F, Gómez de la Torre R, Díaz-Lagares C, Camps M, Ortego N, Sánchez-Román J, BIOGEAS Study Group (2010) Off-label use of rituximab in 196 patients with severe, refractory systemic autoimmune diseases. Clin Exp Rheumatol 28(4):468–476
De Stefano R, Frati E, Nargi F, Menza L (2011) Efficacy of rituximab on pulmonary nodulosis occurring or increasing in patients with rheumatoid arthritis during anti-TNF- α therapy. Clin Exp Rheumatol 29(4):752–753
Child N, O’Carroll M, Berkahn L (2012) Rituximab-induced interstitial lung disease in a patient with immune thrombocytopenia purpura. Intern Med J 42(3):e12–e14
Hadjinicolaou AV, Nisar MK, Parfrey H, Chilvers ER, Ostör AJ (2012) Non-infectious pulmonary toxicity of rituximab: a systematic review. Rheumatology (Oxford) 51(4):653–662
Nakou M, Katsikas G, Sidiropoulos P, Bertsias G, Papadimitraki E, Raptopoulou A, Koutala H, Papadaki HA, Kritikos H, Boumpas DT (2009) Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response. Arthritis Res Ther 11(4):R131
Vos K, Thurlings RM, Wijbrandts CA, van Schaardenburg D, Gerlag DM, Tak PP (2007) Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis. Arthritis Rheumatism 56(3):772–778
Dass S, Rawstron AC, Vital EM, Henshaw K, McGonagle D, Emery P (2008) Highly sensitive B cell analysis predicts response to rituximab therapy in rheumatoid arthritis. Arthritis Rheum 58:2993–2999
Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P, McGonagle D (2011) Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis Rheum 63(3):603–608
Cambridge G, Leandro MJ, Teodorescu M et al (2006) B cell depletion therapy in systemic lupus erythematosus: effect on autoantibody and antimicrobial antibody profiles. Arthritis Rheum 54:3612–3622
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Braun-Moscovici, Y., Butbul-Aviel, Y., Guralnik, L. et al. Rituximab: rescue therapy in life-threatening complications or refractory autoimmune diseases: a single center experience. Rheumatol Int 33, 1495–1504 (2013). https://doi.org/10.1007/s00296-012-2587-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-012-2587-x