Background: Systemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of skin and internal organs (1,2). One of the most common and severe SSc manifestations is interstitial lung disease (ILD) (3).

Objectives: Evaluate tolerability and safety profile of Nintedanib in patients with SSc-related ILD.

Methods: We enrolled 11 consecutive patients (6 female, 5 male, Mean age 62.7 ± 8 SD, disease duration (from the first Non-Raynaud symptom) 8 years (± 7SD) who referred to our Scleroderma Units during the last twelve months. Patients fulfilled EULAR/ACR classification criteria (4) for SSc. Patient was assessed by means of clinical evaluation (baseline and every three months), High Resolution computed tomography (every six month, or sooner), respiratory function test (every three to six months), laboratory work up, nailfold videocapillaroscopy, echocardiogram, and clinical questionnaires (BORG and mMRC).

Results: NSIP was the most frequent HRCT pattern (5 pts, 45%), followed by UIP and UIP/NSIP pattern (respectively 3 pts & 3 pts, 27%). 9 patients showed more than 20% of HRCT pulmonary fibrosis involvement. Only 1 patient had a history of smoking. mRSS was 9.23 (±10SD) points with any significant improvement during the twelve months follow-up (10 ±10SD). 8 pts were on Micophenolate Mophetil (MMF) (7 of them on MMF + steroids), 8 patients were on steroids (mean dose 5 mg/day of Prednisone or equivalent), 3 on rituximab. Main FVC was 2347 ml [+/- 1051 ml] (61.3% predicted) remaining stable. The mmRC decrased from 2.36 at baseline to 2.27 at the end of the follow up and Borg ameliorated from 7.27 at baseline to 6. Two patients were on oxygen therapy (O2 3l/min) with any significant airflow adjustment. Three patients reported irrepressible diarrhea, one patient had a partial intestinal obstruction, one had pulmonary arterial hypertension worsening with an immediate drug withdraw, one patient presented nausea, one irritability. Three patients had a clinical irrelevant weight loss (less than 2 Kg).

Conclusion: we report a preliminary real-life experience on the use of Nintedanib in SSc-related patients, focusing in particular to its tolerability and safety profile. Nintedanib is well tolerated with a low rate of definitive discontinuation due to SAE. Diarrhea is a very frequent adverse event (approximately 5 episodes a day) and had led to dose reduction and/or treatment re-challenge in the majority of patients. Diarrhea seems to ameliorate reducing daily dose of MMF (1 gram/day) or precribing loperamide along with diosmectite and probiotics. FVC, mRSS, HRCT and capilalroscopy pattern remained stable. Further studies are desirable to confirm the usefulness of Nintedanib in progressive ILD, but based on our experience we support the combined use of the anti-fibrotic therapy plus immunomodulatory drugs in early stages of SSc-related ILD

REFERENCES:

[1]LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol [Internet] 1988 [cited 2015 Nov 19];15:202-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3361530

[2]TUFFANELLI DL, WINKELMANN RK. Systemic scleroderma, A clinical study of 727 cases. Arch Dermatol [Internet] 1961 [cited 2016 May 23];84:359-71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/13778561

[3]Hoffmann-Vold AM, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol Lancet Publishing Group; 2020;2:e71-83.

[4]Van Den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: An American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis BMJ Publishing Group; 2013;72:1747-55.

Disclosure of Interests: None declared