Biologika und nicht infektiöse pulmonale Nebenwirkungen

Zusammenfassung

Medikamentös-induzierte Lungenschädigungen werden bei Patienten mit systemisch-rheumatologischen Autoimmunerkrankungen in relevanter Anzahl beobachtet. Im Verlauf des letzten Jahrzehnts zeigte sich ein fast exponentieller Zuwachs neuer krankheitsmodifizierender Präparate bei der Behandlung von Autoimmunerkrankungen. Gegenwärtige Therapiemöglichkeiten beinhalten Tumor-Nekrose-Faktor-α-Inhibitoren, Interleukin-6 Rezeptor Blocker, Interleukin-1 Antagonisten, T-Zell Co-Stimulations-Blocker und B-Zell depletierende Antikörper. Diese Präparate sind effektiv hinsichtlich klinischer Symptome, radiologischer Veränderungen und beeinflussen den Krankheitsverlauf günstig. Allerdings besteht weiterhin Unsicherheit hinsichtlich pulmonaler Toxizitäten unter Therapie. Nicht-infektiöse pulmonale Nebenwirkungen wurden für nahezu alle zugelassenen Biologika berichtet. Das Auftreten pulmonaler Nebenwirkungen ist abhängig von vorbestehenden interstitiellen Lungenveränderungen und bereits etablierter Basismedikation, wobei hier insbesondere Methotrexat zu erwähnen ist. Eine prätherapeutische Beurteilung sollte daher bei Anfangsverdacht eine thorakale Bildgebung und Lungenfunktionsanalytik beinhalten, um einerseits Risikopatienten frühzeitig zu identifizieren und gleichzeitig Ausgangsbefunde für Verlaufsbeurteilungen zu generieren. Bei Manifestation einer interstitiellen Lungenerkrankung ist eine Beendigung der Therapie notwendig, welche in der Regel auch eine systemische Glucokortikoidbehandlung in Verbindung mit weiterer Immunsuppression notwendig macht.

Abstract

Drug-induced pulmonary disorders are not uncommon in patients with systemic rheumatologic autoimmune diseases. Over the last decade there has been an exponential rise in the use of disease-modifying biological agents to treat auto­immune diseases. Current treatment options comprise a group of different biological agents including tumor necrosis factor-α-inhibitors, interleukin-6 receptor blockers, interleukin-1 antagonists, T-cell co-stimulation molecule blockers, and a B-cell depleting antibody. These agents are effective in ameliorating signs, symptoms, radiographic damage, and the natural history of the disease. However, their toxicity profile remains to fully elucidated. Reported non-infectious complications have been published for virtually all biological agents. Incidence rates depend on additional risk factors such as pre-existing interstitial lung disease and/or concomitant methotrexate-treatment. Pre-treatment evaluation should include chest radiographs and pulmonary function tests to discard subclinical interstitial lung disease, especially in patients at high risk of pulmonary disorders or patients with respiratory symptoms or signs. If severe interstitial lung disease develop treatment cessation is mandatory together with initiation of corticosteroid treatment and additional immunosuppressive treatment.

Schlüsselworter

rheumatologische ­Autoimmunerkrankung - Biologika - Lungenerkrankungen

Key words

rheumatological ­autoimmune disease - biologics - lung diseases

• Literatur

• 1 Camus P, Rosenow EC. Latrogenic lung disease. Clin Chest Med 2004; 25: XIII-XIX
• 2 Flieder DB, Travis WD. Pathologic characteristics of drug-induced lung disease. Clin Chest Med 2004; 25: 37-45
• 3 Camus P, Fanton A, Bonniaud P et al. Interstitial lung disease induced by drugs and radiation. Respiration 2004; 71: 301-326
• 4 Coultas DB, Zumwalt RE, Black WC et al. The epidemiology of interstitial lung diseases. Am J Respir Crit Care Med 1994; 150: 967-972
• 5 Thomeer MJ, Costabe U, Rizzato G et al. Comparison of registries of interstitial lung diseases in three European countries. Eur Respir J Suppl 2001; 32: 114s-118s
• 6 American Thoracic Society/European . Respiratory Society International. Multidisciplinary Consensus Classification of the Idiopathic Intersti­tial Pneumonias. Am J Respir Crit Care Med 2002; 165: 277-304
• 7 Blumenauer B, Judd M, Wells G et al. Infliximab for the treatment of rheumatoid arthritis. Cochrane Database Syst Rev 2002; CD003785
• 8 Goldenberg MM. Etanercept, a novel drug for the treatment of patients with severe, active rheumatoid arthritis. Clin Ther 1999; 21: 75-87 discussion 1–2
• 9 Jarvis B, Faulds D. Etanercept: a review of its use in rheumatoid arthritis. Drugs 1999; 57: 945-966
• 10 Navarro-Sarabia F, Ariza-Ariza R, Hernandez-Cruz B et al. Adalimumab for treating rheumatoid arthritis. Cochrane Database Syst Rev 2005; CD005113
• 11 Furst DE. Certolizumab pegol – what role does this new TNF inhibitor have in the treatment of RA?. Nat Clin Pract Rheumatol 2009; 5: 134-135
• 12 Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database Syst Rev 2010; CD008341
• 13 Sebba A. Tocilizumab: the first interleukin-6-receptor inhibitor. Am J Health Syst Pharm 2008; 65: 1413-1418
• 14 Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol 2009; 36: 1118-1125
• 15 Maxwell LJ, Singh JA. Abatacept for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol 2010; 37: 234-245
• 16 Bagust A, Boland A, Hockenhull J et al. Rituximab for the treatment of rheumatoid arthritis. Health Technol Assess 2009; 13 (Suppl. 02) 23-29
• 17 Edwards JCW, Cambridge G, Leandro MJ. B cell depletion therapy in rheumatic disease. Best Pract Res Clin Rheumatol 2006; 20: 915-928
• 18 Edwards JCW, Cambridge G. B-cell targeting in rheumatoid arthritis and other autoimmune diseases. Nat Rev Immunol 2006; 6: 394-403
• 19 Korhonen R, Moilanen E. Anti-CD20 antibody rituximab in the treatment of rheumatoid arthritis. Basic Clin Pharmacol Toxicol 2010; 106: 13-21
• 20 Matsuno O. Drug-induced interstitial lung disease: mechanisms and best diagnostic approaches. Respir Res 2012; 13: 39
• 21 Kim Y-J, Song M, Ryu J-C. Mechanisms underlying methotrexate-induced pulmonary toxicity. Expert Opin Drug Saf 2009; 8: 451-458
• 22 Cleverley JR, Screaton NJ, Hiorns MP et al. Drug-induced lung disease: high-resolution CT and histological findings. Clin Radiol 2002; 57: 292-299
• 23 Behr J. Approach to the diagnosis of interstitial lung disease. Clin Chest Med 2012; 33: 1-10
• 24 Zappala CJ, Latsi PI, Nicholson AG et al. Marginal decline in forced vital capacity is associated with a poor outcome in idiopathic pulmonary fibrosis. Eur Respir J 2010; 35: 830-836
• 25 Meyer KC, Raghu G. Bronchoalveolar lavage for the evaluation of interstitial lung disease: is it clinically useful?. Eur Respir J 2011; 38: 761-769
• 26 Raghu G, Collard HR, Egan JJ et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011; 183: 788-824
• 27 Khasnis AA, Calabrese LH. Tumor necrosis factor inhibitors and lung disease: a paradox of efficacy and risk. Semin Arthritis Rheum 2010; 40: 147-163
• 28 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: 256-264
• 29 Thavarajah K, Wu P, Rhew EJ et al. Pulmonary complications of tumor necrosis factor-targeted therapy. Respir Res 2009; 103: 661-669
• 30 Ramos-Casals M, Perez-Alvarez R, Perez-de-Lis M et al. Pulmonary disorders induced by monoclonal antibodies in patients with rheumatologic autoimmune diseases. Am J Med 2011; 124: 386-394
• 31 Hyrich K, Symmons D, Watson K et al. Baseline comorbidity levels in biologic and standard DMARD treated patients with rheumatoid ­arthritis: results from a national patient register. Ann Rheum Dis 2006; 65: 895-898
• 32 Pincus T, Sokka T. Uniform databases in early arthritis: specific measures to complement classification criteria and indices of clinical change. Clin Exp Rheumatol 2003; 21: S79-S88
• 33 Fleischmann R, Vencovsky J, van Vollenhoven RF et al. Efficacy and safety of certolizumab pegol monotherapy every 4 weeks in patients with rheumatoid arthritis failing previous disease-modifying antirheumatic therapy: the FAST4WARD study. Ann Rheum Dis 2009; 68: 805-811
• 34 Keystone E, Landewé R, van Vollenhoven R et al. Long-term safety and efficacy of certolizumab pegol in combination with methotrexate in the treatment of rheumatoid arthritis: 5-year results from the RAPID 1 trial and open-label extension. Ann Rheum Dis 2013;
• 35 Smolen J, Landewé RB, Mease P et al. Efficacy and safety of certolizumab pegol plus methotrexate in active rheumatoid arthritis: the RAPID 2 study. A randomised controlled trial. Ann Rheum Dis 2009; 68: 797-804
• 36 Weinblatt ME, Fleischmann R, Huizinga TWJ et al. Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study. Rheumatology 2012; 51: 2204-2214
• 37 Glaspole IN, Hoy RF, Ryan PF. A case of certolizumab-induced interstitial lung disease in a patient with rheumatoid arthritis. Rheumatology 2013;
• 38 Lager J, Hilberg O, Løkke A et al. Severe interstitial lung disease following treatment with certolizumab pegol: a case report. Eur Respir Rev 2013; 22: 414-416
• 39 Millar A, McKew J, Taggart A. Fatal fibrosing alveolitis with certolizumab. Rheumatology 2012; 51: 953-955
• 40 Pearce F, Johnson SR, Courtney P. Interstitial lung disease following certolizumab pegol. Rheumatology 2012; 51: 578-580
• 41 Emery P, Fleischmann RM, Moreland LW et al. Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. Arthritis Rheum 2009; 60: 2272-2283
• 42 Inman RD, Davis JC, van der Heijde D et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum 2008; 58: 3402-3412
• 43 Kavanaugh A, McInnes I, Mease P et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009; 60: 976-986
• 44 Keystone EC, Genovese MC, Klareskog L et al. Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study. Ann Rheum Dis 2009; 68: 789-796
• 45 Smolen JS, Kay J, Doyle MK et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 2009; 374: 210-221
• 46 Hadjinicolaou AV, Nisar MK, Parfrey H et al. Non-infectious pulmonary toxicity of rituximab: a systematic review. Rheumatology 2012; 51: 653-662
• 47 Nishimoto N, Miyasaka N, Yamamoto K et al. Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI): significant reduction in disease activity and serum vascular endothelial growth factor by IL-6 receptor inhibition therapy. Mod Rheumatol 2009; 19: 12-19
• 48 Nishimoto N, Yoshizaki K, Miyasaka N et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2004; 50: 1761-1769
• 49 Smolen JS, Beaulieu A, Rubbert-Roth A et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet 2008; 371: 987-997
• 50 Weinblatt ME, Moreland LW, Westhovens R et al. Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integrated analyses of up to 8 years of treatment from the abatacept clinical trial program. J Rheumatol 2013; 40: 787-797