CO:09:3 | Effectiveness and safety of nintedanib in autoimmune systemic diseases: real life data from an Italian multicentre study (Island group) of the Italian Society of Rheumatology

Corrado Campochiaro¹, Paola Conigliaro², Gianluca Sambataro³, Marco Matucci-Cerinic¹, Marco Sebastiani⁴, Gianluca Bajocchi⁵, Angelo Fassio⁶, Elena Treppo⁷, Elisabetta Zanatta⁸, Elena Bartolini⁹, Francesco Ferro¹⁰, Chiara Bazzini¹¹, Nicoletta Del Papa¹², Gemma Lepri¹³, Andrea Lo Monaco¹⁴, Marta Favero¹⁵, Annamaria Iuliano¹⁶, Francesca Li Gobbi¹⁷, Maria Sole Chimenti², Giuseppe Muscato¹⁸, Giacomo De Luca¹, Francesca Cozzini⁴, Lucia Dardani⁵, Francesco Pollastri⁶, Alessandro Gattron⁷, Beatrice Moccaldi⁸, Caterina Antonini⁹, Gaetano La Rocca¹⁰, Ilaria Cavazzana¹¹, Andreina Manfredi^5|19. | ¹IRCCS San Raffaele Hospital, Vita-Salute San Raffaele, Milano; ²U.O.C. Reumatologia Dipartimento di Medicina dei Sistemi Università di Roma-Tor Vergata, Roma; ³Università Kore, Enna; ⁴University of Parma, Azienda Ospedaliera di Piacenza; ⁵UOC Reumatologia, AUSL IRCCS Reggio Emilia; ⁶UOC Reumatologia Università degli Studi di Verona; ⁷Dipartimento di Medicina, Clinica di Reumatologia, Università degli Studi di Udine; ⁸UOC Reumatologia, Dipartimento di Medicina DIMED, Azienda Ospedale Università di Padova; ⁹SC Interaziendale di Reumatologia, Dipartimento di Medicina e Chirurgia, Università di Perugia, Azienda Integrata Università; ¹⁰Dipartimento di Medicina Clinica e Sperimentale UO Reumatologia-Universitaria AOU Pisa; ¹¹U.O. Reumatologia e Immunologia Clinica ASST Spedali Civili di Brescia; ¹²Clinica Reumatologica, Milano; ¹³S.O.D. di Reumatologia AOU Careggi, Firenze; ¹⁴UOC Reumatologia Azienda Ospedaliero-Universitaria Sant'Anna, Ferrara; ¹⁵Internal Medicine I, Department of Medicine, Ca' Foncello Hospital, AULSS2 Marca Trevigiana, Treviso; ¹⁶UOC Reumatologia, AO San Camillo Forlanini, Roma; ¹⁷Rheumatology Unit, S.Giovanni di Dio Hospital, Firenze; ¹⁸Department of Clinical and Experimental Medicine, Regional Referral Center for Rare Lung Disease, Policlinico, Catania; ¹⁹Università degli Studi di Modena e Reggio Emilia, Italy

Background. Nintedanib (NTD) has been shown to be useful to slow functional decline of progressive fibrosing interstitial lung disease also in Autoimmune Systemic Diseases (ASDs) beside systemic sclerosis (SSc) and rheumatoid arthritis (RA) after the positive results of the INBUILD trial. Here we describe the effectiveness and safety of NTD in ASDs in a real-life setting.

Materials and Methods. The clinical data of ASDs patients with ILD (excluded SSc and RA) treated with NTD from 17 Italian centres were retrospectively evaluated at 12 months prior to NTD introduction; at baseline, and at 12 months after NTD introduction. The following parameters were recorded: ASD clinical features, NTD tolerability, pulmonary function tests (PFTs). Progressors were defined as a drop in %pFVC >= 5 and/or %pDLCO >= 10 within 12 months.

Results. 114 ASD-ILD patients (46.5% male, mean age 69 ± 10 years, median disease duration 5.5 (2-12) years) treated with NTD were identified. Disease features are summarized in Table 1. The most common ASD was anti-synthetase syndrome (31, 27.2%) and the most common antibody was anti-Ro52 (44, 38.6%), most (57.9%) had been previously treated with immunosuppressants. At baseline, 107 (93.9%) patients were on immunosuppressants (see Table 1), with 74 (64.9%) patients on steroid with a median dose of 5 (1.25 – 7.5). Baseline HRCT was available in 109 patients and it showed an UIP pattern in 43 (39.4%) and a NSIP pattern in 66 (60.6%) patients. A significant decline in %pFVC and in %pDLCO was observed in the 12 months prior to NTD introduction (82.4 ± 21 versus 71 ± 16, p <0.001 and 51 ± 17 versus 44 ± 13, p <0.001, respectively) with 54 (69%) being classified as progressors. At 12 months after NTD introduction, follow-up data were available for 54 patients and they showed an improvement in both %pFVC (72 ± 15 to 75 ± 17, p < 0.001) and %pDLCO (43 ± 15 to 45 ± 17; p < 0.001); moreover, the percentage of progressors was significantly lower (69% versus 26%, p < 0.001). The dosage of NTD was reduced to 100 mg BID in 44 (38.6%) patients after a median time of 5 (3 – 9) months, and suspended in 19 (16.7%) patients after a median time of 3 (1-8) months, see Figure 1. During the follow-up, 10 (8.8%) patients died.

Conclusions. In a real-life clinical scenario, NTD, in combination with immunosuppressants, may improve lung function in patients with ASDs. NTD seems to be well-tolerated and the rate of drug suspension is low. Our data support early evaluation of ILD in wide range of ASDs in order to identify patients eligible for antifibrotic drug in association to immunosuppressants.