The safety of biologic therapies in RA-associated interstitial lung disease

Key Points

  • Anti-TNF therapy has improved outcomes in rheumatoid arthritis (RA), but has also been associated with serious respiratory adverse events (SRAEs)

  • Biologic therapy might cause SRAEs by inducing idiosyncratic reactions, accelerating pre-existing ILD, modifying ILD into a more injurious phenotype or increasing susceptibility to infection

  • The risks associated with anti-TNF therapy in patients with RA-associated ILD (RA-ILD) remain uncertain; whether other biologic agents are safer is also still unclear

  • Given this uncertainty, careful assessment of patients before treatment and strict subsequent monitoring is required, particularly in patients at high risk of ILD progression, regardless of chosen treatment

  • We need to move towards a better understanding of the natural history of RA-ILD and the roles of new therapies in the management of this disease, which requires well-conducted research

Abstract

Interstitial lung disease (ILD) is a common extra-articular manifestation associated with increased morbidity and mortality in patients with rheumatoid arthritis (RA). Early case reports of serious respiratory adverse events (SRAEs) following treatment with anti-TNF agents have led to concerns about biologic therapy in patients with RA-associated ILD (RA-ILD), and a tendency for biologic agents targeting factors other than TNF to be prescribed in such patients. At present, the appropriateness of such decisions is not clear. Given that the therapeutic goal for RA is remission, clinicians increasingly face the challenge of choosing the optimal biologic agent in patients with RA-ILD and uncontrolled joint disease. However, no evidence-based guidelines exist to guide physicians in deciding whether to commence biologic therapy in this setting, or in selecting which drug is most appropriate. Herein, we review the evidence for the comparative pulmonary safety of anti-TNF agents and non-TNF-targeting biologic agents in RA-ILD. In addition, we propose a framework for assessment of baseline disease severity to guide treatment decisions, and for monitoring during therapy. Because of substantial gaps in the available evidence, we also describe a research agenda aimed at obtaining data that will help inform future clinical practice.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Classification of ILDs.
Figure 2: Suggested algorithm for assessment, monitoring and management of patients with RA-ILD on biologic therapy.

References

  1. 1

    Ostor, A. J. et al. Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. J. Rheumatol. 33, 622–628 (2006).

    PubMed  Google Scholar 

  2. 2

    Castelino, F. V. & Varga, J. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management. Arthritis Res. Ther. 12, 213 (2010).

    PubMed  PubMed Central  Google Scholar 

  3. 3

    Turesson, C., O'Fallon, W. M., Crowson, C. S., Gabriel, S. E. & Matteson, E. L. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann. Rheum. Dis. 62, 722–727 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4

    Peno-Green, L., Lluberas, G., Kingsley, T. & Brantley, S. Lung injury linked to etanercept therapy. Chest 122, 1858–1860 (2002).

    PubMed  Google Scholar 

  5. 5

    Liote, H., Liote, F., Seroussi, B., Mayaud, C. & Cadranel, J. Rituximab-induced lung disease: a systematic literature review. Eur. Respir. J. 35, 681–687 (2010).

    CAS  PubMed  Google Scholar 

  6. 6

    O'Connor, M. B., Abdullah, M. F., O'Donovan, N. & Phelan, M. J. Rituximab-induced pulmonary disease. Rheumatol. Int. 32, 2955–2956 (2012).

    PubMed  Google Scholar 

  7. 7

    Wada, T. et al. A case of rheumatoid arthritis complicated with deteriorated interstitial pneumonia after the administration of abatacept [Japanese]. Nihon Rinsho Meneki Gakkai Kaishi. 35, 433–438 (2012).

    PubMed  Google Scholar 

  8. 8

    Ikegawa, K., Hanaoka, M., Ushiki, A., Yamamoto, H. & Kubo, K. A case of organizing pneumonia induced by tocilizumab. Intern. Med. 50, 2191–2193 (2011).

    CAS  PubMed  Google Scholar 

  9. 9

    Kawashiri, S. Y., Kawakami, A., Sakamoto, N., Ishimatsu, Y. & Eguchi, K. A fatal case of acute exacerbation of interstitial lung disease in a patient with rheumatoid arthritis during treatment with tocilizumab. Rheumatol. Int. 32, 4023–4026 (2012).

    PubMed  Google Scholar 

  10. 10

    Wendling, D. et al. Exacerbation of combined pulmonary fibrosis and emphysema syndrome during tocilizumab therapy for rheumatoid arthritis. Joint Bone Spine http://dx.doi.org/10.1016/j.jbspin.2013.03.009.

  11. 11

    Thrall, R. S., Vogel, S. N., Evans, R. & Shultz, L. D. Role of tumor necrosis factor-α in the spontaneous development of pulmonary fibrosis in viable motheaten mutant mice. Am. J. Pathol. 151, 1303–1310 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Ortiz, L. A. et al. Expression of TNF and the necessity of TNF receptors in bleomycin-induced lung injury in mice. Exp. Lung. Res. 24, 721–743 (1998).

    CAS  PubMed  Google Scholar 

  13. 13

    Piguet, P. F., Ribaux, C., Karpuz, V., Grau, G. E. & Kapanci, Y. Expression and localization of tumor necrosis factor- α and its mRNA in idiopathic pulmonary fibrosis. Am. J. Pathol. 143, 651–655 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Kapanci, Y., Desmouliere, A., Pache, J. C., Redard, M. & Gabbiani, G. Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis. Possible role of transforming growth factor β and tumor necrosis factor α. Am. J. Respir. Crit. Care Med. 152, 2163–2169 (1995).

    CAS  PubMed  Google Scholar 

  15. 15

    Raghu, G. et al. Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 178, 948–955 (2008).

    CAS  PubMed  Google Scholar 

  16. 16

    US National Library of Medicine. ClinicalTrials.gov [online], (2013).

  17. 17

    Winthrop, K. L. Infections and biologic therapy in rheumatoid arthritis: our changing understanding of risk and prevention. Rheum. Dis. Clin. North Am. 38, 727–745 (2012).

    PubMed  Google Scholar 

  18. 18

    Lipsky, P. E. et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N. Engl. J. Med. 343, 1594–1602 (2000).

    CAS  PubMed  Google Scholar 

  19. 19

    Klareskog, L. et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363, 675–681 (2004).

    CAS  PubMed  Google Scholar 

  20. 20

    Weinblatt, M. E. et al. Adalimumab, a fully human anti-tumor necrosis factor α monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum. 48, 35–45 (2003).

    CAS  PubMed  Google Scholar 

  21. 21

    Maini, R. N. et al. Sustained improvement over two years in physical function, structural damage, and signs and symptoms among patients with rheumatoid arthritis treated with infliximab and methotrexate. Arthritis Rheum. 50, 1051–1065 (2004).

    CAS  PubMed  Google Scholar 

  22. 22

    van Vollenhoven, R. F. et al. Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial): 1-year results of a randomised trial. Lancet 374, 459–466 (2009).

    CAS  PubMed  Google Scholar 

  23. 23

    van der Heijde, D. et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum 54, 1063–1074 (2006).

    CAS  PubMed  Google Scholar 

  24. 24

    Breedveld, F. C. et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 54, 26–37 (2006).

    CAS  PubMed  Google Scholar 

  25. 25

    Burmester, G. R. et al. Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial. Ann. Rheum. Dis. 66, 732–739 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26

    Ostor, A. J., Crisp, A. J., Somerville, M. F. & Scott, D. G. Fatal exacerbation of rheumatoid arthritis associated fibrosing alveolitis in patients given infliximab. BMJ 329, 1266 (2004).

    PubMed  PubMed Central  Google Scholar 

  27. 27

    Antoniou, K. M. et al. Infliximab therapy in pulmonary fibrosis associated with collagen vascular disease. Clin. Exp. Rheumatol. 25, 23–28 (2007).

    CAS  PubMed  Google Scholar 

  28. 28

    Vassallo, R., Matteson, E. & Thomas, C. F., Jr. Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor necrosis factor-α inhibition. Chest 122, 1093–1096 (2002).

    PubMed  Google Scholar 

  29. 29

    Bargagli, E., Galeazzi, M. & Rottoli, P. Infliximab treatment in a patient with rheumatoid arthritis and pulmonary fibrosis. Eur. Respir. J. 24, 708 (2004).

    CAS  PubMed  Google Scholar 

  30. 30

    Perez-Alvarez, R. et al. Interstitial lung disease induced or exacerbated by TNF-targeted therapies: analysis of 122 cases. Semin. Arthritis Rheum. 41, 256–264 (2011).

    CAS  PubMed  Google Scholar 

  31. 31

    Dascalu, C., Mrejen-Shakin, K. & Bandagi, S. Adalimumab-induced acute pneumonitis in a patient with rheumatoid arthritis. J. Clin. Rheumatol. 16, 172–174 (2010).

    PubMed  Google Scholar 

  32. 32

    Yamazaki, H., Isogai, S., Sakurai, T. & Nagasaka, K. A case of adalimumab-associated interstitial pneumonia with rheumatoid arthritis. Mod. Rheumatol. 20, 518–521 (2010).

    PubMed  Google Scholar 

  33. 33

    Cho, S. K., Oh, I. H., Park, C. K., Bae, S. C. & Sung, Y. K. Etanercept induced organizing pneumonia in a patient with rheumatoid arthritis. Rheumatol. Int. 32, 1055–1057 (2012).

    CAS  PubMed  Google Scholar 

  34. 34

    Horai, Y. et al. Eternacept for the treatment of patients with rheumatoid arthritis and concurrent interstitial lung disease. J. Clin. Pharm. Ther. 37, 117–121 (2012).

    CAS  PubMed  Google Scholar 

  35. 35

    Sakaida, H., Komase, Y. & Takemura, T. Organizing pneumonia in a patient with rheumatoid arthritis treated with etanercept. Mod. Rheumatol. 20, 611–616 (2010).

    PubMed  Google Scholar 

  36. 36

    Yokoyama, T. et al. A case of etanercept-induced pneumonitis [Japanese]. Nihon Kokyuki Gakkai Zasshi 47, 870–874 (2009).

    PubMed  Google Scholar 

  37. 37

    Hadjinicolaou, A. V. et al. Non-infectious pulmonary complications of newer biological agents for rheumatic diseases—a systematic literature review. Rheumatology (Oxford) 50, 2297–2305 (2011).

    Google Scholar 

  38. 38

    Pearce, F., Johnson, S. R. & Courtney, P. Interstitial lung disease following certolizumab pegol. Rheumatology (Oxford) 51, 578–580 (2012).

    CAS  Google Scholar 

  39. 39

    Millar, A., McKew, J. & Taggart, A. Fatal fibrosing alveolitis with certolizumab. Rheumatology (Oxford) 51, 953–955 (2012).

    CAS  Google Scholar 

  40. 40

    Glaspole, I. N., Hoy, R. F. & Ryan, P. F. A case of certolizumab-induced interstitial lung disease in a patient with rheumatoid arthritis. Rheumatology (Oxford) 52, 2302–2304 (2013).

    Google Scholar 

  41. 41

    Lager, J., Hilberg, O., Lokke, A. & Bendstrup, E. Severe interstitial lung disease following treatment with certolizumab pegol: a case report. Eur. Respir. Rev. 22, 414–416 (2013).

    PubMed  Google Scholar 

  42. 42

    Wolfe, F., Caplan, L. & Michaud, K. Rheumatoid arthritis treatment and the risk of severe interstitial lung disease. Scand. J. Rheumatol. 36, 172–178 (2007).

    CAS  PubMed  Google Scholar 

  43. 43

    Herrinton, L. J. et al. Association between anti-TNF-α therapy and interstitial lung disease. Pharmacoepidemiol. Drug Saf. 22, 394–402 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44

    Dixon, W. G., Hyrich, K. L., Watson, K. D., Lunt, M. & Symmons, D. P. Influence of anti-TNF therapy on mortality in patients with rheumatoid arthritis-associated interstitial lung disease: results from the British Society for Rheumatology Biologics Register. Ann. Rheum. Dis. 69, 1086–1091 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45

    Kim, Y. J. et al. Mortality in patients with rheumatoid arthritis-associated interstitial lung disease treated with an anti-tumour necrosis factor agent [abstract 0210]. Ann. Rheum. Dis. 72 (Suppl. 3), 444 (2013).

    Google Scholar 

  46. 46

    US Food and Drug Administration. Therapeutic Biological Products Approvals [online], (2003).

  47. 47

    US Food and Drug Administration. Rituximab for moderate to severe rheumatoid arthritis [online], (2006).

  48. 48

    European Medicines Agency. Mabthera: procedural steps taken and scientific information after authorisation [online], (2013).

  49. 49

    Haraoui, B., Bokarewa, M., Kallmeyer, I. & Bykerk, V. P. Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an inadequate response to 1 prior tumor necrosis factor inhibitor: the RESET Trial. J. Rheumatol. 38, 2548–2556 (2011).

    CAS  PubMed  Google Scholar 

  50. 50

    Emery, P. et al. 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. 54, 1390–1400 (2006).

    CAS  PubMed  Google Scholar 

  51. 51

    Emery, P. et al. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX Inadequate Responders (SERENE)). Ann. Rheum. Dis. 69, 1629–1935 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52

    Mease, P. J. et al. Efficacy and safety of retreatment in patients with rheumatoid arthritis with previous inadequate response to tumor necrosis factor inhibitors: results from the SUNRISE trial. J. Rheumatol. 37, 917–927 (2010).

    CAS  PubMed  Google Scholar 

  53. 53

    Edwards, J. C. et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572–2581 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54

    Hadjinicolaou, A. V., Nisar, M. K., Parfrey, H., Chilvers, E. R. & Ostor, A. J. Non-infectious pulmonary toxicity of rituximab: a systematic review. Rheumatology (Oxford) 51, 653–662 (2012).

    CAS  Google Scholar 

  55. 55

    Keir, G. J. et al. Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy. Eur. Respir. J. 40, 641–648 (2012).

    CAS  PubMed  Google Scholar 

  56. 56

    Matteson, E. L. et al. Open-label, pilot study of the safety and clinical effects of rituximab in patients with rheumatoid arthritis-associated interstitial pneumonia. Open J. Rheumatol. Autoimmune Dis. 2, 53–58 (2012).

    Google Scholar 

  57. 57

    Becerra, E. & Leandro, M. J. Safety and efficacy of rituximab in patients with rheumatoid arthritis and lung involvement [abstract 502]. Arthritis Rheum. 64 (Suppl. S10), S220 (2012).

    Google Scholar 

  58. 58

    Dass, S. et al. Safety of rituximab in patients with rheumatoid arthritis and concomitant lung disease [abstract 205]. Rheumatology (Oxford) 50 (Suppl. 3), iii121 (2011).

    Google Scholar 

  59. 59

    Weinblatt, M. E. 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. 40, 787–797 (2013).

    CAS  PubMed  Google Scholar 

  60. 60

    US Food and Drug Administration. Abatacept for moderate to severe rheumatoid arthritis [online], (2005).

  61. 61

    Nishimoto, N. et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 50, 1761–1769 (2004).

    CAS  PubMed  Google Scholar 

  62. 62

    Smolen, J. S. 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 371, 987–997 (2008).

    CAS  PubMed  Google Scholar 

  63. 63

    Nishimoto, N. 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. 19, 12–19 (2009).

    CAS  PubMed  Google Scholar 

  64. 64

    Gabay, C. et al. Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 318, 1541–1550 (2013).

    Google Scholar 

  65. 65

    US Food and Drug Administration. Tocilizumab for moderate to severe rheumatoid arthritis [online], (2009).

  66. 66

    European Medicines Agency. RoActemra, tocilizumab: authorisation details 16/01/2009 [online], (2009).

  67. 67

    Periodic Safety Update Report 1053705 (Roche Products Limited, 2012).

  68. 68

    Yamanaka, H. et al. Efficacy and tolerability of tocilizumab in rheumatoid arthritis patients seen in daily clinical practice in Japan: results from a retrospective study (REACTION study). Mod. Rheumatol. 21, 122–133 (2011).

    CAS  PubMed  Google Scholar 

  69. 69

    Mohr, M. & Jacobi, A. M. Interstitial lung disease in rheumatoid arthritis: response to IL-6R blockade. Scand. J. Rheumatol. 40, 400–401 (2011).

    CAS  PubMed  Google Scholar 

  70. 70

    Koike, T. et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann. Rheum. Dis. 70, 2148–2151 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Smolen, J. S., van der Heijde, D., Machold, K. P., Aletaha, D. & Landewe, R. Proposal for a new nomenclature of disease-modifying antirheumatic drugs. Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2013-204317.

  72. 72

    US Food and Drug Administration. Xeljanz (Tofacinitib) approval for moderate to severe rheumatoid arthritis [online], (2012).

  73. 73

    van Vollenhoven, R. F. et al. Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. N. Engl. J. Med. 367, 508–519 (2012).

    CAS  PubMed  Google Scholar 

  74. 74

    Fleischmann, R. et al. Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. N. Engl. J. Med. 367, 495–507 (2012).

    CAS  PubMed  Google Scholar 

  75. 75

    Stenton, C. The MRC breathlessness scale. Occup. Med. (Lond.) 58, 226–227 (2008).

    Google Scholar 

  76. 76

    Danoff, S. K., Terry, P. B. & Horton, M. R. A clinician's guide to the diagnosis and treatment of interstitial lung diseases. South. Med. J. 100, 579–587 (2007).

    PubMed  Google Scholar 

  77. 77

    Egan, J. J., Martinez, F. J., Wells, A. U. & Williams, T. Lung function estimates in idiopathic pulmonary fibrosis: the potential for a simple classification. Thorax 60, 270–273 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Ley, B. et al. A multidimensional index and staging system for idiopathic pulmonary fibrosis. Ann. Intern. Med. 156, 684–691 (2012).

    PubMed  Google Scholar 

  79. 79

    Latsi, P. I. et al. Fibrotic idiopathic interstitial pneumonia: the prognostic value of longitudinal functional trends. Am. J. Respir. Crit. Care Med. 168, 531–537 (2003).

    PubMed  Google Scholar 

  80. 80

    Raghu, G. 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. 183, 788–824 (2011).

    PubMed  PubMed Central  Google Scholar 

  81. 81

    Hamblin, M. J. & Horton, M. R. Rheumatoid arthritis-associated interstitial lung disease: diagnostic dilemma. Pulm. Med. 2011, 872120 (2011).

    PubMed  PubMed Central  Google Scholar 

  82. 82

    Flaherty, K. R. et al. Radiological versus histological diagnosis in UIP and NSIP: survival implications. Thorax 58, 143–148 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Kim, E. J. et al. Usual interstitial pneumonia in rheumatoid arthritis-associated interstitial lung disease. Eur. Respir. J. 35, 1322–1328 (2010).

    CAS  PubMed  Google Scholar 

  84. 84

    Wells, A. U. & Hogaboam, C. M. Update in diffuse parenchymal lung disease 2007. Am. J. Respir. Crit. Care Med. 177, 580–584 (2008).

    CAS  PubMed  Google Scholar 

  85. 85

    Goh, N. S. et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am. J. Respir. Crit. Care Med. 177, 1248–1254 (2008).

    PubMed  Google Scholar 

  86. 86

    Sathi, N., Urwin, T., Desmond, S. & Dawson, J. K. Patients with limited rheumatoid arthritis-related interstitial lung disease have a better prognosis than those with extensive disease. Rheumatology (Oxford) 50, 620 (2011).

    Google Scholar 

  87. 87

    Mann, D. L. et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation 109, 1594–1602 (2004).

    CAS  PubMed  Google Scholar 

  88. 88

    Kwon, H. J., Cote, T. R., Cuffe, M. S., Kramer, J. M. & Braun, M. M. Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann. Intern. Med. 138, 807–811 (2003).

    PubMed  Google Scholar 

  89. 89

    Saketkoo, L. A. et al. Developing an index for disease activity and therapeutic response in connective tissue disease related interstitial lung disease: results from a Delphi exercise: delivering a consensus on domains. Arthritis Rheum. 64, 1713 (2012).

    Google Scholar 

  90. 90

    Cottin, V., Capron, F., Grenier, P. & Cordier, J. F. Diffuse idiopathic interstitial pneumonias. International multidisciplinary consensus classification by the American Thoracic Society and the European Respiratory Society, principal clinico-pathological entities, and diagnosis [French]. Rev. Mal. Respir. 21, 299–318 (2004).

    CAS  PubMed  Google Scholar 

  91. 91

    Collard, H. R. et al. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 168, 538–542 (2003).

    PubMed  Google Scholar 

  92. 92

    Bottomley, A., Jones, D. & Claassens, L. Patient-reported outcomes: assessment and current perspectives of the guidelines of the Food and Drug Administration and the reflection paper of the European Medicines Agency. Eur. J. Cancer. 45, 347–353 (2009).

    PubMed  Google Scholar 

  93. 93

    Speight, J. & Barendse, S. M. FDA guidance on patient reported outcomes. BMJ 340, c2921 (2010).

    PubMed  Google Scholar 

  94. 94

    Pope, J. Measures of systemic sclerosis (scleroderma): Health Assessment Questionnaire (HAQ) and Scleroderma HAQ (SHAQ), physician- and patient-rated global assessments, Symptom Burden Index (SBI), University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Scale (UCLA SCTC GIT) 2.0, Baseline Dyspnea Index (BDI) and Transition Dyspnea Index (TDI) (Mahler's Index), Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), and Raynaud's Condition Score (RCS). Arthritis Care Res. (Hoboken) 63, S98–S111 (2011).

    Google Scholar 

  95. 95

    Minnock, P., Kirwan, J. & Bresnihan, B. Fatigue is a reliable, sensitive and unique outcome measure in rheumatoid arthritis. Rheumatology (Oxford) 48, 1533–1536 (2009).

    Google Scholar 

  96. 96

    Boers, M., Brooks, P., Strand, C. V. & Tugwell, P. The OMERACT filter for outcome measures in rheumatology. J. Rheumatol. 25, 198–199 (1998).

    CAS  PubMed  Google Scholar 

  97. 97

    Makol, A., Wright, K. & Matteson, E. L. Safe use of antirheumatic agents in patients with comorbidities. Rheum. Dis. Clin. North Am. 38, 771–793 (2012).

    PubMed  Google Scholar 

  98. 98

    Zink, A. et al. European biologicals registers: methodology, selected results and perspectives. Ann. Rheum. Dis. 68, 1240–1246 (2009).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank J. Ryu for reviewing the draft manuscript before submission. M. Jani is a Medical Research Council (MRC) Clinical Training Fellow supported by the North West England MRC Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the MRC (grant number G1000417/94,909), with additional financial support from ICON, GSK, AstraZeneca and the Medical Evaluation Unit. W. G. Dixon acknowledges research funding from the MRC (Clinician Scientist Fellowship; G0902272).

Author information

Affiliations

Authors

Contributions

M. Jani and W. G. Dixon contributed to all stages of the preparation of the manuscript for submission, N. Hirani and E. L. Matteson made substantial contributions to discussion of content and review/editing of the manuscript before submission.

Corresponding author

Correspondence to William G. Dixon.

Ethics declarations

Competing interests

M. Jani has received reimbursement for attending symposia from UCB and Pfizer. N. Hirani has received reimbursement for attending symposia from Boehringer-Ingelheim and has received research funding from the AstraZeneca. E. L. Matteson and W. G. Dixon declare no competing interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jani, M., Hirani, N., Matteson, E. et al. The safety of biologic therapies in RA-associated interstitial lung disease. Nat Rev Rheumatol 10, 284–294 (2014). https://doi.org/10.1038/nrrheum.2013.197

Download citation

Further reading