Multidimensional improvement in connective tissue disease-associated interstitial lung disease: Two courses of pulse dose methylprednisolone followed by low-dose prednisone and tacrolimus
Corresponding Author
Yasuhiko Yamano
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Correspondence: Yasuhiko Yamano, Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi 489-8642, Japan. Email: [email protected]Search for more papers by this authorHiroyuki Taniguchi
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Search for more papers by this authorYasuhiro Kondoh
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Search for more papers by this authorMasahiko Ando
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
Search for more papers by this authorKensuke Kataoka
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Search for more papers by this authorTaiki Furukawa
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Search for more papers by this authorTakeshi Johkoh
Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Health Teachers, Itami, Japan
Search for more papers by this authorJunya Fukuoka
Department of Laboratory of Pathology, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorKoji Sakamoto
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Search for more papers by this authorYoshinori Hasegawa
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Search for more papers by this authorCorresponding Author
Yasuhiko Yamano
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Correspondence: Yasuhiko Yamano, Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi 489-8642, Japan. Email: [email protected]Search for more papers by this authorHiroyuki Taniguchi
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Search for more papers by this authorYasuhiro Kondoh
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Search for more papers by this authorMasahiko Ando
Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan
Search for more papers by this authorKensuke Kataoka
Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan
Search for more papers by this authorTaiki Furukawa
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Search for more papers by this authorTakeshi Johkoh
Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public Health Teachers, Itami, Japan
Search for more papers by this authorJunya Fukuoka
Department of Laboratory of Pathology, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorKoji Sakamoto
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Search for more papers by this authorYoshinori Hasegawa
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
Search for more papers by this authorABSTRACT
Background and objective
Corticosteroids and immunosuppressive agents are considered mainstays of therapy for connective tissue disease-related interstitial lung disease (CTD-ILD); however, tacrolimus with corticosteroid therapy has not been fully investigated. Our objectives were to examine the multidimensional therapeutic benefit and tolerability of the combined therapy for the initial treatment of patients with CTD-ILD.
Methods
In this retrospective case series, we identified consecutive CTD-ILD patients treated with tacrolimus plus intravenous (i.v.) methylprednisolone (1000 mg i.v. 3 days a week for 2 weeks) followed by low-dose prednisolone (10 mg/day). We assessed the multidimensional therapeutic benefit and tolerability including lung physiology, exercise capacity, exercise oxygen desaturation, modified Medical Research Council (MMRC) and St George's Respiratory Questionnaire (SGRQ).
Results
A total of 26 ILD patients with the underlying CTD diagnoses included 11 with rheumatoid arthritis, 9 with dermatomyositis, 4 with Sjögren's syndrome and 2 others. From baseline to 12 months, the combined therapy significantly improved forced vital capacity (FVC; 77.8% to 94.6%, P < 0.001), diffusing capacity of the lung for carbon monoxide (DLCO; 66.1% to 75.1%, P < 0.001), 6-min walk distance (6MWD; 530 to 568 m, P = 0.02), lowest oxygen saturation on pulse oximetry (SpO2; 85% to 89%, P = 0.01), MMRC (1.3 to 0.8, P = 0.01) and SGRQ (38 to 21, P < 0.001). During the study period, only one patient's therapy was discontinued due to an adverse event and none had a life-threatening adverse event attributed to the combined therapy.
Conclusion
In our cohort of CTD-ILD, two courses of pulse dose methylprednisolone therapy followed by prednisone and oral tacrolimus appeared to be well tolerated, and to have multidimensional efficacy.
Supporting Information
| Filename | Description |
|---|---|
| resp13365-sup-0001-suppinfo.docWord document, 188.5 KB |
Figure S1 Flow chart of patients. Figure S2 Annual change from baseline over time in peripheral muscle forces. Table S1 Baseline characteristics and annual change from baseline over time in outcome measures. |
| resp13365-sup-0002-visualabstract.pptxWord document, 288.5 KB |
Visual Abstract Multidimensional improvement in CTD-ILD. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Fischer A, du Bois R. Interstitial lung disease in connective tissue disorders. Lancet 2012; 380: 689–98.
- 2Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M et al. Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. 2006; 354: 2655–66.
- 3Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir. Med. 2016; 4: 708–19.
- 4Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Ther. Drug Monit. 1995; 17: 584–91.
- 5Suzuki K, Saito K, Tsujimura S, Nakayamada S, Yamaoka K, Sawamukai N, Iwata S, Nawata M, Nakano K, Tanaka Y. Tacrolimus, a calcineurin inhibitor, overcomes treatment unresponsiveness mediated by P-glycoprotein on lymphocytes in refractory rheumatoid arthritis. J. Rheumatol. 2010; 37: 512–20.
- 6Garcia-Carrasco M, Mendoza-Pinto C, Macias Diaz S, Vera-Recabarren M, Vazquez de Lara L, Mendez Martinez S, Soto-Santillan P, Gonzalez-Ramirez R, Ruiz-Arguelles A. P-glycoprotein in autoimmune rheumatic diseases. Autoimmun. Rev. 2015; 14: 594–600.
- 7Nagano J, Iyonaga K, Kawamura K, Yamashita A, Ichiyasu H, Okamoto T, Suga M, Sasaki Y, Kohrogi H. Use of tacrolimus, a potent antifibrotic agent, in bleomycin-induced lung fibrosis. Eur. Respir. J. 2006; 27: 460–9.
- 8Wilkes MR, Sereika SM, Fertig N, Lucas MR, Oddis CV. Treatment of antisynthetase-associated interstitial lung disease with tacrolimus. Arthritis Rheum. 2005; 52: 2439–46.
- 9Witt LJ, Demchuk C, Curran JJ, Strek ME. Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease. Pulm. Pharmacol. Ther. 2016; 36: 46–52.
- 10Kurita T, Yasuda S, Oba K, Odani T, Kono M, Otomo K, Fujieda Y, Oku K, Bohgaki T, Amengual O et al. The efficacy of tacrolimus in patients with interstitial lung diseases complicated with polymyositis or dermatomyositis. Rheumatology (Oxford) 2015; 54: 39–44.
- 11Saketkoo LA, Matteson EL, Brown KK, Seibold JR, Strand V; Connective Tissue Disease-Related Interstitial Lung Disease Special Interest Group. Developing disease activity and response criteria in connective tissue disease-related interstitial lung disease. J. Rheumatol. 2011; 38: 1514–8.
- 12Saketkoo LA, Mittoo S, Huscher D, Khanna D, Dellaripa PF, Distler O, Flaherty KR, Frankel S, Oddis CV, Denton CP et al.; CTD-ILD Special Interest Group. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax 2014; 69: 428–36.
- 13Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2010; 62: 2569–81.
- 14Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS et al.; European Study Group on Classification Criteria for Sjögren's Syndrome. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann. Rheum. Dis. 2002; 61: 554–8.
- 15Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N. Engl. J. Med. 1975; 292: 344–7.
- 16Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis sine myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J. Am. Acad. Dermatol. 2006; 54: 597–613.
- 17van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE et al. 2013 Classification criteria for systemic sclerosis: an American College of Rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2013; 65: 2737–47.
- 18Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA et al.; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. 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.
- 19Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P et al. Standardisation of spirometry. Eur. Respir. J. 2005; 26: 319–38.
- 20Macintyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur. Respir. J. 2005; 26: 720–35.
- 21 ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am. J. Respir. Crit. Care Med. 2002; 166: 111–7.
- 22Mahler DA, Wells CK. Evaluation of clinical methods for rating dyspnea. Chest 1988; 93: 580–6.
- 23Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. Am. Rev. Respir. Dis. 1992; 145: 1321–7.
- 24National Isometric Muscle Strength Database Consortium. Muscular weakness assessment: use of normal isometric strength data. Arch. Phys. Med. Rehabil. 1996; 77: 1251–5.
- 25Khanna D, Mittoo S, Aggarwal R, Proudman SM, Dalbeth N, Matteson EL, Brown K, Flaherty K, Wells AU, Seibold JR et al. Connective tissue disease-associated interstitial lung diseases (CTD-ILD) – report from OMERACT CTD-ILD Working Group. J. Rheumatol. 2015; 42: 2168–71.
- 26Swigris JJ, Wamboldt FS, Behr J, du Bois RM, King TE, Raghu G, Brown KK. The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important difference. Thorax 2010; 65: 173–7.
- 27Swigris JJ, Brown KK, Behr J, du Bois RM, King TE, Raghu G, Wamboldt FS. The SF-36 and SGRQ: validity and first look at minimum important differences in IPF. Respir. Med. 2010; 104: 296–304.
- 28Suzuki A, Kondoh Y, Swigris JJ, Ando M, Kimura T, Kataoka K, Yamano Y, Furukawa T, Numata M, Sakamoto K et al. Performance of the St George's Respiratory Questionnaire in patients with connective tissue disease-associated interstitial lung disease. Respirology 2018; 23: 851–859.
- 29Mok CC, Ying KY, Yim CW, Siu YP, Tong KH, To CH, Ng WL. Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up. Ann. Rheum. Dis. 2016; 75: 30–6.
- 30Watanabe N, Sakamoto K, Taniguchi H, Kondoh Y, Kimura T, Kataoka K, Ono K, Fukuoka J, Nishiyama O, Hasegawa Y. Efficacy of combined therapy with cyclosporin and low-dose prednisolone in interstitial pneumonia associated with connective tissue disease. Respiration 2014; 87: 469–77.
- 31Harigai M, Hara M, Kamatani N, Kashiwazaki S. Nation-wide survey for the treatment with cyclosporin A of interstitial pneumonia associated with collagen diseases. Ryumachi 1999; 39: 819–28.
- 32Dumont FJ. FK506, an immunosuppressant targeting calcineurin function. Curr. Med. Chem. 2000; 7: 731–48.
- 33Webster AC, Woodroffe RC, Taylor RS, Chapman JR, Craig JC. Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data. BMJ 2005; 331: 810.
- 34Haddad EM, McAlister VC, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database Syst. Rev. 2006; 4: CD005161.
- 35Staab-Weijnitz CA, Fernandez IE, Knuppel L, Maul J, Heinzelmann K, Juan-Guardela BM, Hennen E, Preissler G, Winter H, Neurohr C et al. FK506-binding protein 10, a potential novel drug target for idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2015; 192: 455–67.
- 36Chartrand S, Fischer A. Management of connective tissue disease-associated interstitial lung disease. Rheum. Dis. Clin. North Am. 2015; 41: 279–94.
- 37Suh GY, Kang EH, Chung MP, Lee KS, Han J, Kitaichi M, Kwon OJ. Early intervention can improve clinical outcome of acute interstitial pneumonia. Chest 2006; 129: 753–61.
- 38 Idiopathic Pulmonary Fibrosis Clinical Research Network, Raghu G, Anstrom KJ, King TE Jr, Lasky JA, Martinez FJ. Prednisone, azathioprine, and N-acetylcysteine for pulmonary fibrosis. N. Engl. J. Med. 2012; 366: 1968–77.
- 39Flaherty KR, Colby TV, Travis WD, Toews GB, Mumford J, Murray S, Thannickal VJ, Kazerooni EA, Gross BH, Lynch JP 3rd et al. Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease. Am. J. Respir. Crit. Care Med. 2003; 167: 1410–5.
- 40Song JW, Do KH, Kim MY, Jang SJ, Colby TV, Kim DS. Pathologic and radiologic differences between idiopathic and collagen vascular disease-related usual interstitial pneumonia. Chest 2009; 136: 23–30.
- 41Hanada M, Sakamoto N, Ishimatsu Y, Kakugawa T, Obase Y, Kozu R, Senjyu H, Izumikawa K, Mukae H, Kohno S. Effect of long-term treatment with corticosteroids on skeletal muscle strength, functional exercise capacity and health status in patients with interstitial lung disease. Respirology 2016; 21: 1088–93.
- 42Ge Y, Zhou H, Shi J, Ye B, Peng Q, Lu X, Wang G. The efficacy of tacrolimus in patients with refractory dermatomyositis/polymyositis: a systematic review. Clin. Rheumatol. 2015; 34: 2097–103.
