Semin Respir Crit Care Med 2014; 35(02): 265-273
DOI: 10.1055/s-0034-1371531
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Immunosuppression for Connective Tissue Disease–Related Pulmonary Disease

Toby M. Maher
1   NIHR Biological Research Unit, Royal Brompton Hospital, Sydney Street, London, United Kingdom
2   Leukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London, United Kingdom
3   Centre for Inflammation and Tissue Repair, University College London, Rayne Institute, London, United Kingdom
› Author Affiliations
Further Information

Publication History

Publication Date:
25 March 2014 (online)

Abstract

With improvements in the systemic treatment of the various connective tissue diseases (CTDs) the pulmonary complications of these conditions are now, for many patients, the major cause of morbidity and impaired quality of life. Furthermore, at least in scleroderma, pulmonary disease has become the leading cause of death for this patient group. Although, the pathogenesis of CTD-related pulmonary disease is poorly understood there is an assumption that it arises as a sequelae of immune-mediated injury to the lung. As a result, immunosuppressant agents form the mainstay of treatment for pulmonary disease occurring in the context of CTD. There is, however, a paucity of clinical trial data available to inform treatment decisions across the spectrum of CTD-related pulmonary disease. The best available evidence has been generated in scleroderma-associated interstitial lung disease. Therefore, treatment decisions are informed by registry data, case series, and individual case reports. With this in mind, corticosteroids together with azathioprine and mycophenolate mofetil are widely used for the management of mild disease or as a maintenance therapy, while cyclophosphamide and rituximab have emerged as treatments for refractory or rapidly progressive disease. This article examines the data underpinning the use of different immunosuppressants in CTD-associated pulmonary disease while highlighting limitations in the existing knowledge base and identifying questions for future clinical study.

Note

T.M. is in receipt of unrestricted academic industry grants from GSK and Novartis. In the last 3 years T.M. or his institution have received advisory board or consultancy fees from; Actelion, Boehringer Ingelheim, GSK, InterMune, Novartis, Lanthio, Takeda, Sanofi-Aventis, and UCB. T.M. has received speaker's fees from UCB, Boehringer Ingelheim, InterMune, and AstraZeneca. T.M. has participated as an investigator in industry sponsored clinical trials run by Boehringer Ingelheim, GSK, InterMune, Novartis, Roche, and Celgene.


 
  • References

  • 1 Tyndall AJ, Bannert B, Vonk M , et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 2010; 69 (10) 1809-1815
  • 2 Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet 2012; 380 (9842) 689-698
  • 3 Kim EJ, Collard HR, King Jr TE. Rheumatoid arthritis-associated interstitial lung disease: the relevance of histopathologic and radiographic pattern. Chest 2009; 136 (5) 1397-1405
  • 4 Fischer A, Swigris JJ, du Bois RM , et al. Anti-synthetase syndrome in ANA and anti-Jo-1 negative patients presenting with idiopathic interstitial pneumonia. Respir Med 2009; 103 (11) 1719-1724
  • 5 Hoyles RK, Ellis RW, Wellsbury J , et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheum 2006; 54 (12) 3962-3970
  • 6 Tashkin DP, Elashoff R, Clements PJ , et al; Scleroderma Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med 2006; 354 (25) 2655-2666
  • 7 Khanna D, Brown KK, Clements PJ , et al. Systemic sclerosis-associated interstitial lung disease-proposed recommendations for future randomized clinical trials. Clin Exp Rheumatol 2010; 28 (2) (Suppl. 58) S55-S62
  • 8 Walker KM, Pope J ; participating members of the Scleroderma Clinical Trials Consortium (SCTC); Canadian Scleroderma Research Group (CSRG). Treatment of systemic sclerosis complications: what to use when first-line treatment fails—a consensus of systemic sclerosis experts. Semin Arthritis Rheum 2012; 42 (1) 42-55
  • 9 Launay D, Humbert M, Berezne A , et al. Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. Chest 2011; 140 (4) 1016-1024
  • 10 Opitz C, Klein-Weigel PF, Riemekasten G. Systemic sclerosis - a systematic overview: part 2 - immunosuppression, treatment of SSc-associated vasculopathy, and treatment of pulmonary arterial hypertension. Vasa 2011; 40 (1) 20-30
  • 11 Devouassoux G, Cottin V, Lioté H , et al; Groupe d'Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires (GERM”O”P). Characterisation of severe obliterative bronchiolitis in rheumatoid arthritis. Eur Respir J 2009; 33 (5) 1053-1061
  • 12 Magnusson J, Westin J, Andersson LM, Brittain-Long R, Riise GC. The impact of viral respiratory tract infections on long-term morbidity and mortality following lung transplantation: a retrospective cohort study using a multiplex PCR panel. Transplantation 2013; 95 (2) 383-388
  • 13 Gregson AL, Wang X, Weigt SS , et al. Interaction between Pseudomonas and CXC chemokines increases risk of bronchiolitis obliterans syndrome and death in lung transplantation. Am J Respir Crit Care Med 2013; 187 (5) 518-526
  • 14 Vos R, Vanaudenaerde BM, Ottevaere A , et al. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer?. J Heart Lung Transplant 2010; 29 (12) 1358-1368
  • 15 Abbassi-Ghadi N, Kumar S, Cheung B , et al. Anti-reflux surgery for lung transplant recipients in the presence of impedance-detected duodenogastroesophageal reflux and bronchiolitis obliterans syndrome: a study of efficacy and safety. J Heart Lung Transplant 2013; 32 (6) 588-595
  • 16 Tansey D, Wells AU, Colby TV , et al. Variations in histological patterns of interstitial pneumonia between connective tissue disorders and their relationship to prognosis. Histopathology 2004; 44 (6) 585-596
  • 17 Kowal-Bielecka O, Landewé R, Avouac J , et al; EUSTAR Co-Authors. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis 2009; 68 (5) 620-628
  • 18 Ando K, Motojima S, Doi T , et al. Effect of glucocorticoid monotherapy on pulmonary function and survival in Japanese patients with scleroderma-related interstitial lung disease. Respir Investig 2013; 51 (2) 69-75
  • 19 Gordon PA, Winer JB, Hoogendijk JE, Choy EH. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database Syst Rev 2012; 8: CD003643
  • 20 Kotani T, Makino S, Takeuchi T , et al. Early intervention with corticosteroids and cyclosporin A and 2-hour postdose blood concentration monitoring improves the prognosis of acute/subacute interstitial pneumonia in dermatomyositis. J Rheumatol 2008; 35 (2) 254-259
  • 21 Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years?. Chest 2010; 138 (6) 1464-1474
  • 22 Lazor R, Vandevenne A, Pelletier A, Leclerc P, Court-Fortune I, Cordier JF. Cryptogenic organizing pneumonia. Characteristics of relapses in a series of 48 patients. The Groupe d'Etudes et de Recherche sur les Maladles “Orphelines” Pulmonaires (GERM”O”P). Am J Respir Crit Care Med 2000; 162 (2 Pt 1): 571-577
  • 23 Wells AU, Latsi P, McCune WJ. Daily cyclophosphamide for scleroderma: are patients with the most to gain underrepresented in this trial?. Am J Respir Crit Care Med 2007; 176 (10) 952-953
  • 24 Domiciano DS, Bonfá E, Borges CT , et al. A long-term prospective randomized controlled study of non-specific interstitial pneumonia (NSIP) treatment in scleroderma. Clin Rheumatol 2011; 30 (2) 223-229
  • 25 Broad K, Pope JE. The efficacy of treatment for systemic sclerosis interstitial lung disease: results from a meta-analysis. Med Sci Monit 2010; 16 (9) RA187-RA190
  • 26 Wanchu A, Suryanaryana BS, Sharma S, Sharma A, Bambery P. High-dose prednisolone and bolus cyclophosphamide in interstitial lung disease associated with systemic sclerosis: a prospective open study. Int J Rheum Dis 2009; 12 (3) 239-242
  • 27 Bérezné A, Ranque B, Valeyre D , et al. Therapeutic strategy combining intravenous cyclophosphamide followed by oral azathioprine to treat worsening interstitial lung disease associated with systemic sclerosis: a retrospective multicenter open-label study. J Rheumatol 2008; 35 (6) 1064-1072
  • 28 White B, Moore WC, Wigley FM, Xiao HQ, Wise RA. Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis. Ann Intern Med 2000; 132 (12) 947-954
  • 29 Poormoghim H, Moradi Lakeh M, Mohammadipour M, Sodagari F, Toofaninjed N. Cyclophosphamide for scleroderma lung disease: a systematic review and meta-analysis. Rheumatol Int 2012; 32 (8) 2431-2444
  • 30 Mittoo S, Wigley FM, Wise RA, Woods A, Xiao H, Hummers LK. Long term effects of cyclophosphamide treatment on lung function and survival in scleroderma patients with interstitial lung disease. Open Rheumatol J 2011; 5: 1-6
  • 31 Tochimoto A, Kawaguchi Y, Hara M , et al. Efficacy and safety of intravenous cyclophosphamide pulse therapy with oral prednisolone in the treatment of interstitial lung disease with systemic sclerosis: 4-year follow-up. Mod Rheumatol 2011; 21 (3) 296-301
  • 32 Theodore AC, Tseng CH, Li N, Elashoff RM, Tashkin DP. Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study. Chest 2012; 142 (3) 614-621
  • 33 Roth MD, Tseng CH, Clements PJ , et al; Scleroderma Lung Study Research Group. Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum 2011; 63 (9) 2797-2808
  • 34 Dheda K, Lalloo UG, Cassim B, Mody GM. Experience with azathioprine in systemic sclerosis associated with interstitial lung disease. Clin Rheumatol 2004; 23 (4) 306-309
  • 35 Bodolay E, Szekanecz Z, Dévényi K , et al. Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD). Rheumatology (Oxford) 2005; 44 (5) 656-661
  • 36 Okada M, Suzuki K, Matsumoto M , et al. Intermittent intravenous cyclophosphamide pulse therapy for the treatment of active interstitial lung disease associated with collagen vascular diseases. Mod Rheumatol 2007; 17 (2) 131-136
  • 37 Corte TJ, Ellis R, Renzoni EA , et al. Use of intravenous cyclophosphamide in known or suspected, advanced non-specific interstitial pneumonia. Sarcoidosis Vasc Diffuse Lung Dis 2009; 26 (2) 132-138
  • 38 Goh NS, Desai SR, Veeraraghavan S , et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med 2008; 177 (11) 1248-1254
  • 39 Jayne D. Treating vasculitis with conventional immunosuppressive agents. Cleve Clin J Med 2012; 79 (Suppl. 03) S46-S49
  • 40 Casian A, Jayne D. Management of alveolar hemorrhage in lung vasculitides. Semin Respir Crit Care Med 2011; 32 (3) 335-345
  • 41 Schwarz MI, Zamora MR, Hodges TN, Chan ED, Bowler RP, Tuder RM. Isolated pulmonary capillaritis and diffuse alveolar hemorrhage in rheumatoid arthritis and mixed connective tissue disease. Chest 1998; 113 (6) 1609-1615
  • 42 Cordier JF, Cottin V. Alveolar hemorrhage in vasculitis: primary and secondary. Semin Respir Crit Care Med 2011; 32 (3) 310-321
  • 43 Lynch III JP, Tazelaar H. Wegener granulomatosis (granulomatosis with polyangiitis): evolving concepts in treatment. Semin Respir Crit Care Med 2011; 32 (3) 274-297
  • 44 Stone JH, Merkel PA, Spiera R , et al; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 2010; 363 (3) 221-232
  • 45 Paone C, Chiarolanza I, Cuomo G , et al. Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy. Clin Exp Rheumatol 2007; 25 (4) 613-616
  • 46 Yu KH, Wu YJ, Kuo CF , et al. Survival analysis of patients with dermatomyositis and polymyositis: analysis of 192 Chinese cases. Clin Rheumatol 2011; 30 (12) 1595-1601
  • 47 Chung L, Liu J, Parsons L , et al. Characterization of connective tissue disease-associated pulmonary arterial hypertension from REVEAL: identifying systemic sclerosis as a unique phenotype. Chest 2010; 138 (6) 1383-1394
  • 48 Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H. The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol 2005; 114 (2) 154-163
  • 49 Smolen JS, Landewé R, Breedveld FC , et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2013;
  • 50 Atzeni F, Boiardi L, Sallì S, Benucci M, Sarzi-Puttini P. Lung involvement and drug-induced lung disease in patients with rheumatoid arthritis. Expert Rev Clin Immunol 2013; 9 (7) 649-657
  • 51 Roubille C, Haraoui B. Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: A systematic literature review. Semin Arthritis Rheum 2013;
  • 52 Sathi N, Chikura B, Kaushik VV, Wiswell R, Dawson JK. How common is methotrexate pneumonitis? A large prospective study investigates. Clin Rheumatol 2012; 31 (1) 79-83
  • 53 Coppo P, Clauvel JP, Bengoufa D, Oksenhendler E, Lacroix C, Lassoued K. Inflammatory myositis associated with anti-U1-small nuclear ribonucleoprotein antibodies: a subset of myositis associated with a favourable outcome. Rheumatology (Oxford) 2002; 41 (9) 1040-1046
  • 54 Kim P, Grossman JM. Treatment of mixed connective tissue disease. Rheum Dis Clin North Am 2005; 31 (3) 549-565 , viii
  • 55 Vanthuyne M, Blockmans D, Westhovens R , et al. A pilot study of mycophenolate mofetil combined to intravenous methylprednisolone pulses and oral low-dose glucocorticoids in severe early systemic sclerosis. Clin Exp Rheumatol 2007; 25 (2) 287-292
  • 56 Simeón-Aznar CP, Fonollosa-Plá V, Tolosa-Vilella C, Selva-O'Callaghan A, Solans-Laqué R, Vilardell-Tarrés M. Effect of mycophenolate sodium in scleroderma-related interstitial lung disease. Clin Rheumatol 2011; 30 (11) 1393-1398
  • 57 Koutroumpas A, Ziogas A, Alexiou I, Barouta G, Sakkas LI. Mycophenolate mofetil in systemic sclerosis-associated interstitial lung disease. Clin Rheumatol 2010; 29 (10) 1167-1168
  • 58 Gerbino AJ, Goss CH, Molitor JA. Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest 2008; 133 (2) 455-460
  • 59 Swigris JJ, Olson AL, Fischer A , et al. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest 2006; 130 (1) 30-36
  • 60 Fischer A, Brown KK, Du Bois RM , et al. Mycophenolate mofetil improves lung function in connective tissue disease-associated interstitial lung disease. J Rheumatol 2013; 40 (5) 640-646
  • 61 Tzouvelekis A, Galanopoulos N, Bouros E , et al. Effect and safety of mycophenolate mofetil or sodium in systemic sclerosis-associated interstitial lung disease: a meta-analysis. Pulm Med 2012; 2012: 143637
  • 62 Labirua-Iturburu A, Selva-O'Callaghan A, Martínez-Gómez X, Trallero-Araguás E, Labrador-Horrillo M, Vilardell-Tarrés M. Calcineurin inhibitors in a cohort of patients with antisynthetase-associated interstitial lung disease. Clin Exp Rheumatol 2013; 31 (3) 436-439
  • 63 Matsuki Y, Yamashita H, Takahashi Y , et al. Diffuse alveolar damage in patients with dermatomyositis: a six-case series. Mod Rheumatol 2012; 22 (2) 243-248
  • 64 Ando M, Miyazaki E, Yamasue M , et al. Successful treatment with tacrolimus of progressive interstitial pneumonia associated with amyopathic dermatomyositis refractory to cyclosporine. Clin Rheumatol 2010; 29 (4) 443-445
  • 65 Polosa R, Edwards CJ. Tacrolimus for antisynthetase syndrome with interstitial lung disease?. Eur Respir J 2008; 32 (1) 244-245 , author reply 245–246
  • 66 Guglielmi S, Merz TM, Gugger M, Suter C, Nicod LP. Acute respiratory distress syndrome secondary to antisynthetase syndrome is reversible with tacrolimus. Eur Respir J 2008; 31 (1) 213-217
  • 67 Ochi S, Nanki T, Takada K , et al. Favorable outcomes with tacrolimus in two patients with refractory interstitial lung disease associated with polymyositis/dermatomyositis. Clin Exp Rheumatol 2005; 23 (5) 707-710
  • 68 Oddis CV, Sciurba FC, Elmagd KA, Starzl TE. Tacrolimus in refractory polymyositis with interstitial lung disease. Lancet 1999; 353 (9166) 1762-1763
  • 69 Cavagna L, Caporali R, Abdì-Alì L, Dore R, Meloni F, Montecucco C. Cyclosporine in anti-Jo1-positive patients with corticosteroid-refractory interstitial lung disease. J Rheumatol 2013; 40 (4) 484-492
  • 70 Leandro MJ, Cambridge G, Ehrenstein MR, Edwards JC. Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis. Arthritis Rheum 2006; 54 (2) 613-620
  • 71 Isaacs JD, Cohen SB, Emery P , et al. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis 2013; 72 (3) 329-336
  • 72 Keystone EC, Cohen SB, Emery P , et al. Multiple courses of rituximab produce sustained clinical and radiographic efficacy and safety in patients with rheumatoid arthritis and an inadequate response to 1 or more tumor necrosis factor inhibitors: 5-year data from the REFLEX study. J Rheumatol 2012; 39 (12) 2238-2246
  • 73 Emery P, Fleischmann R, Filipowicz-Sosnowska A , et al; DANCER Study Group. The efficacy and safety of rituximab in patients with active rheumatoid arthritis despite methotrexate treatment: results of a phase IIB randomized, double-blind, placebo-controlled, dose-ranging trial. Arthritis Rheum 2006; 54 (5) 1390-1400
  • 74 Jones RB, Tervaert JW, Hauser T , et al; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med 2010; 363 (3) 211-220
  • 75 Arnold DM, Dentali F, Crowther MA , et al. Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 2007; 146 (1) 25-33
  • 76 Daoussis D, Liossis SN, Tsamandas AC , et al. Effect of long-term treatment with rituximab on pulmonary function and skin fibrosis in patients with diffuse systemic sclerosis. Clin Exp Rheumatol 2012; 30 (2) (Suppl. 71) S17-S22
  • 77 Daoussis D, Liossis SN, Tsamandas AC , et al. Is there a role for B-cell depletion as therapy for scleroderma? A case report and review of the literature. Semin Arthritis Rheum 2010; 40 (2) 127-136
  • 78 Keir GJ, Maher TM, Hansell DM , et al. Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy. Eur Respir J 2012; 40 (3) 641-648
  • 79 Keir GJ, Maher TM, Ming D , et al. Rituximab in severe, treatment-refractory interstitial lung disease [published online ahead of print November 29, 2013]. Respirology . doi: 10.1111/resp.12214
  • 80 Giuggioli D, Manfredi A, Colaci M, Manzini CU, Antonelli A, Ferri C. Systemic sclerosis and cryoglobulinemia: our experience with overlapping syndrome of scleroderma and severe cryoglobulinemic vasculitis and review of the literature. Autoimmun Rev 2013; 12 (11) 1058-1063
  • 81 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 2013; 33 (6) 1495-1504
  • 82 Daniels CE, Wilkes MC, Edens M , et al. Imatinib mesylate inhibits the profibrogenic activity of TGF-beta and prevents bleomycin-mediated lung fibrosis. J Clin Invest 2004; 114 (9) 1308-1316
  • 83 Sabnani I, Zucker MJ, Rosenstein ED , et al. A novel therapeutic approach to the treatment of scleroderma-associated pulmonary complications: safety and efficacy of combination therapy with imatinib and cyclophosphamide. Rheumatology (Oxford) 2009; 48 (1) 49-52
  • 84 Spiera RF, Gordon JK, Mersten JN , et al. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis 2011; 70 (6) 1003-1009
  • 85 Khanna D, Saggar R, Mayes MD , et al. A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum 2011; 63 (11) 3540-3546
  • 86 Distler JH, Manger B, Spriewald BM, Schett G, Distler O. Treatment of pulmonary fibrosis for twenty weeks with imatinib mesylate in a patient with mixed connective tissue disease. Arthritis Rheum 2008; 58 (8) 2538-2542
  • 87 De Lauretis A, Sestini P, Pantelidis P , et al. Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol 2013; 40 (4) 435-446
  • 88 Liu X, Das AM, Seideman J , et al. The CC chemokine ligand 2 (CCL2) mediates fibroblast survival through IL-6. Am J Respir Cell Mol Biol 2007; 37 (1) 121-128
  • 89 Moodley YP, Scaffidi AK, Misso NL , et al. Fibroblasts isolated from normal lungs and those with idiopathic pulmonary fibrosis differ in interleukin-6/gp130-mediated cell signaling and proliferation. Am J Pathol 2003; 163 (1) 345-354
  • 90 Yoshida M, Sakuma J, Hayashi S , et al. A histologically distinctive interstitial pneumonia induced by overexpression of the interleukin 6, transforming growth factor beta 1, or platelet-derived growth factor B gene. Proc Natl Acad Sci U S A 1995; 92 (21) 9570-9574
  • 91 Keidel SM, Hoyles RK, Wilkinson NM. Efficacy of tocilizumab for interstitial lung disease in an undifferentiated autoinflammatory disorder partially responsive to anakinra. Rheumatology (Oxford) 2013;
  • 92 Mohr M, Jacobi AM. Interstitial lung disease in rheumatoid arthritis: response to IL-6R blockade. Scand J Rheumatol 2011; 40 (5) 400-401
  • 93 Thompson B, Corris P, Miller JA, Cooper RG, Halsey JP, Isaacs JD. Alemtuzumab (Campath-1H) for treatment of refractory polymyositis. J Rheumatol 2008; 35 (10) 2080-2082
  • 94 Horai Y, Miyamura T, Shimada K , et al. Eternacept for the treatment of patients with rheumatoid arthritis and concurrent interstitial lung disease. J Clin Pharm Ther 2012; 37 (1) 117-121
  • 95 Perez-Alvarez R, Perez-de-Lis M, Diaz-Lagares C , et al. Interstitial lung disease induced or exacerbated by TNF-targeted therapies: analysis of 122 cases. Semin Arthritis Rheum 2011; 41 (2) 256-264
  • 96 Ramos-Casals M, Brito-Zerón P, Muñoz S , et al. Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore) 2007; 86 (4) 242-251
  • 97 Park JK, Yoo HG, Ahn DS, Jeon HS, Yoo WH. Successful treatment for conventional treatment-resistant dermatomyositis-associated interstitial lung disease with adalimumab. Rheumatol Int 2012; 32 (11) 3587-3590
  • 98 Zong M, Dorph C, Dastmalchi M , et al. Anakinra treatment in patients with refractory inflammatory myopathies and possible predictive response biomarkers: a mechanistic study with 12 months follow-up. Ann Rheum Dis 2013;
  • 99 Furlan A, Botsios C, Ruffatti A, Todesco S, Punzi L. Antisynthetase syndrome with refractory polyarthritis and fever successfully treated with the IL-1 receptor antagonist, anakinra: A case report. Joint Bone Spine 2008; 75 (3) 366-367
  • 100 Douglas WW, Tazelaar HD, Hartman TE , et al. Polymyositis-dermatomyositis-associated interstitial lung disease. Am J Respir Crit Care Med 2001; 164 (7) 1182-1185
  • 101 Suzuki Y, Hayakawa H, Miwa S , et al. Intravenous immunoglobulin therapy for refractory interstitial lung disease associated with polymyositis/dermatomyositis. Lung 2009; 187 (3) 201-206
  • 102 Bakewell CJ, Raghu G. Polymyositis associated with severe interstitial lung disease: remission after three doses of IV immunoglobulin. Chest 2011; 139 (2) 441-443