AB0868 IMMUNE Checkpoint Inhibitor-Associated Myopathy

Acknowledgements: NIL. Disclosure of Interests: Hikaru Hirose: None declared, Tomoaki Higuchi: None declared, Kae Takagi: None declared, Akiko Tochimoto: None declared, Yasushi Kawaguchi: None declared, Masayoshi Harigai Speakers bureau: AbbVie Japan GK; AstraZeneca K.K.; Ayumi Pharmaceutical Co.; Boehringer Ingelheim Japan Inc.; Bristol Myers Squibb Co., Ltd.; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Eli Lilly Japan K.K.; GlaxoSmithKline K.K.; Gilead Sciences Inc.; Janssen Pharmaceutical K.K.; Kissei Pharmaceutical Co., Ltd.; Nippon Kayaku Co., Ltd.; Nippon Shinyaku Co., Ltd.; Novartis Japan; Pfizer Japan Inc.; CIMIC Holdings Co., Ltd.; Mitsubishi Tanabe Pharma Co.; Teijin Pharma Ltd.; and UCB Japan Co. Ltd., Consultant of: AbbVie; Boehringer-Ingelheim; Bristol Myers Squibb Co.; Kissei Pharmaceutical Co., Ltd.; and Teijin Pharma Ltd., Grant/research support from: AbbVie Japan GK; Asahi Kasei Corp.; Astellas Pharma Inc.; Ayumi Pharmaceutical Co.; Boehringer Ingelheim Japan, Inc.; Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc., Eisai Co., Ltd.; Kaken Pharmaceutical Co., Ltd.; Kissei Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Co.; Nippon Kayaku Co., Ltd.; Sekisui Medical; Taisho Pharmaceutical Co., Ltd.; and Teijin Pharma Ltd. DOI: 10.1136/annrheumdis-2023-eular.1745 AB0867 LOW STARTING DOSE AND TITRATION OF NINTEDANIB FOR SSC-ILD: ANALYSIS OF TOLERABILITY IN A SINGLE-CENTER COHORT Keywords: Systemic sclerosis, Real-world evidence, Lungs E. Fiorentini1, F. Bonomi1, L. Cometi1, G. Lepri1, S. Bellando-Randone1, S. Guiducci1. 1Careggi University Hospital, Rheumatology, Firenze, Italy Background: Interstitial lung disease (SSc-ILD) is a common manifestation of Systemic Sclerosis (SSc) and to date few therapies are available [1]. Nintedanib (NTD) is a promising drug, but its use is often limited by intolerance, mainly by gastrointestinal adverse events (GI AEs). As reported in the SENSCIS trial [2] GI AEs related to NTD treatment (150mg bid) occur in >70% of cases, in particular diarrhea (75.7%), nausea (36.7%), vomit (24.7%), weight loss (11.8%), abdominal pain (11.5%) and alterations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (13.9%). Objectives: We investigated the safety and tolerability of an up-titration strategy of NTD until the maximum tolerated dose (max 150mg bid) in our cohort of SScILD patients. Methods: Evaluation of SSc patients followed at our Rheumatology Unit, treated with NTD according to clinical indication with a dose escalation regimen: 100mg die for 7 days, then 100mg bid for 7 days, then 150mg + 100mg/die for 7 days, and finally 150mg bid. At baseline, demographic, clinical and disease features were collected. NTD GI tolerability was clinically evaluated at 1 (T1), 3 (T3) and 6 (T6) months from the beginning of the treatment. Results: 12 SSc-ILD patients were enrolled, all females, with a mean age of 62.5 ± 12.7 years and disease duration of 9.2 ± 6.8 years (from the first non-Raynaud symptom). The more frequent disease specific antibody was anti-topoisomerase I (50%) followed by anti-centromere (8.3%). ILD pattern at HRCT was non-specific interstitial pneumonia (NSIP) in 25% of the patients, fibrosing NSIP in 50% and usual interstitial pneumonia (UIP) in 25%. The mean FVC % predicted was 71.2% (± 15.9%) and the mean DLCO 50.4% (± 14.4%). Indications for NTD prescription were fibrosis >10% (25%), FVC decline 5-10% + clinical or imaging worsening (33.3%), clinical and/or imaging worsening (41.7%). GI involvement due to SSc at baseline was present in 75% of patients: gastrointestinal reflux in 66.7%, dysmotility, vomit, and dyspepsia in 8.3% each. Table 1 shows GI AEs at T1, T3 and T6 from NTD beginning. At T6 50% of patients had nausea, 50% diarrhea, 37.5% abdominal pain and 25% referred weight loss. No one showed vomit and AST/ALT alterations. Only 3 patients reached 150mg bid (Figure 1), while 4 got at least to 100 mg bid and 1 patient suspended the drug after 3 months due to vomit. Conclusion: These data, although limited to a small cohort, suggest that a gradual dose escalation of NTD in SSc-ILD may improve the tolerability of the drug, with a lower incidence of GI AEs (≤50%) and AST/ALT elevation. Although only 3 patients reached the maximum dose, most of the cohort managed to do at least 100 mg bid. This approach can be a good compromise in the management of ILD in SSc patients, knowing that the dose reduction to 100 mg bid does not significantly compromise the efficacy of NTD in reducing disease progression [3]–[5]. Studies of larger populations are needed to support these data. REFERENCES: [1] P. Khedoe et al. Front Immunol, 2020, doi: 10.3389/fimmu.2020.01990 [2] O. Distler et al, N Engl J Med, 2019, doi: 10.1056/NEJMoa1903076 [3] L. Richeldi et al. N Engl J Med, 2014, doi: 10.1056/NEJMoa1402584 [4] B. Crestani et al. Lancet Respir Med, 2019, doi: 10.1016/ S2213-2600(18)30339-4 [5] L. Richeldi et al. N Engl J Med, 2011, doi: 10.1056/NEJMoa1103690 1647 Table 1. GI AEs during NTD treatment Nausea, n (%) Not present New onset Stable Improved Worsened Vomit, n (%) Not present New onset Stable Improved Worsened Diarrhea, n (%) Not present New onset Stable Improved Worsened Abdominal pain, n (%) Not present New onset Stable Improved Worsened AST/ALT elevation, n (%) Weight loss, n (%) T1 (n=12) T3 (n=12) T6 (n=8) 9 (75%) 3 (25%) 7 (58.3%) 2 (16.7%) 1 (8.3%) 4 (50%) 2 (25%) 1 (12.5%) 1 (12.5%) 2 (16.7%) 10 (83.4%) 2 (16.6%) 9 (75%) 1 (8.3%) 8 (100%) 2 (16.7%) 1 2 (100%) 11 (91.6%) 1 (8.3%) 4 (50%) 3 (37.5%) 1 (12.5%) 9 (75%) 3 (25%) 9 (75%) 1 (8.3%) 1 (8.3%) 1 (8.3%) 0 0 0 2 (16.7%) 5 (62.5%) 1 (12.5%) 1 (12.5%) 1 (12.5%) 0 2 (≠ from the T3) (25%) Figure 1. NTD dosages Acknowledgements: NIL. Disclosure of Interests: None Declared. DOI: 10.1136/annrheumdis-2023-eular.1762 AB0868 IMMUNE CHECKPOINT INHIBITOR-ASSOCIATED MYOPATHY Keywords: Myositis, Targeted synthetic drugs M. Pavía Pascual1, N. De La Torre Rubio1, M. Machattou1, P. Navarro Palomo1, C. Navarro Joven1, M. Alonso de Francisco1, C. Barbadillo Mateos1, C. Merino Argumánez1, H. Godoy1, M. Fernandez Castro1, B. Garcia-Magallon1, J. Sanz1, L. F. De Villa1, J. L. Andréu Sánchez1, J. Campos Esteban1. 1Hospital Universitario Puerta de Hierro Majadahonda, Rheumatology, Madrid, Spain Background: In recent decades, immunotherapy has changed the management and prognosis of cancer patients. Immune checkpoint inhibitors, such as those targeting PD-1 and PD-L1, are used for some types of cancer; however, their use has been associated with the appearance of immune-mediated adverse events. Among these, those related to the field of rheumatology are relatively frequent, joint involvement being the most common, followed by muscle involvement (myalgias 4%, myositis 1%). Objectives: To describe oncologic patients who developed immune checkpoint inhibitors- related myositis. Methods: All patients from the oncology department of a tertiary hospital, referred to rheumatology and diagnosed with immune-mediated myositis due to immune checkpoint inhibitors were collected. A descriptive analysis was performed. Results: Five patients were analyzed, 60% male, with a mean age of 65.8 years (56-78 years). The types of cancer were: melanoma (n=2), gastroesophageal Ann Rheum Dis: first published as 10.1136/annrheumdis-2023-eular.2384 on 30 May 2023. Downloaded from http://ard.bmj.com/ on February 17, 2024 by guest. Protected by copyright. Scientific Abstracts Scientific Abstracts junction cancer (n=1), cavum cancer (n=1) and pancreatic cancer (n=1); all in advanced stages with lymph node and/or metastatic involvement. The immunotherapy employed was: Nivolumab (PD-1 inhibitor) in three patients, Pembrolizumab (PD-1 inhibitor) in one patient and Darvalumab (PD-L1 inhibitor) in one patient; all at standard doses. Mean time from onset of symptoms was 4 months from drug initiation (1-10 months). In all 5 cases, the drug was discontinued with the onset of clinical symptoms and oral prednisone was prescribed at a dose between 10 and 20 mg per day. The symptom present in all patients was pain and weakness of proximal limbs (100%). In addition, one patient had ankle arthritis and another had dermatomyositis with typical cutaneous involvement (heliotrope erythema, V sign). In 3 patients there was an elevation of CK levels that resolved one month after discontinuation of the drug. Also, 3 patients, developed myositis-specific antibodies (AntiPM75 and Anti MI2, anti-PL7 and anti-TIF1gamma) that disappeared with drug withdrawal. One patient had anti-Ro52 and Ro60 antibodies that remain positive. Two patients underwent muscle MRI: one showed fatty infiltration in the gluteal musculature and atrophy with fatty infiltration in the right rectus femoris (image); in the other patient, signs of inflammatory myositis in the bilateral adductor group and in the right gluteus medius and gluteus minimus and fibrosing myositis in the iliac muscle was described. In both cases, the signs of myositis had disappeared in the control PET scan 5 months after drug discontinuation. In 4 patients, symptoms subsided in less than one month. One patient required the association of methotrexate to achieve corticosteroid withdrawal. Conclusion: In our hospital, a total of 5 patients undergoing oncological treatment with immune checkpoint inhibitors have developed, in a mean time of 4 months from the start of the drug, a myopathy associated in 60% with the appearance of myositis-specific antibodies. This represents 1.8% of the total number of patients treated with these three drugs in our hospital. Withdrawal of the drug and treatment with prednisone at intermediate doses allowed clinical remission and normalization of laboratory and imaging tests. Objectives: The aim of the study is to study the level of major autoantibodies in patients with systemic scleroderma who are positive for anti-U1ribonucleoprotein. Methods: The study included 55 patients (48 women and 7 men, mean age 41.5±11.5 years), positive for anti-U1ribonucleoprotein and meeting the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2013 classification criteria for systemic scleroderma. Defined autoantibodies (AT): rheumatoid factor (RF), antibodies to cyclic citrullinated peptide (ACCP), anticentromeric antibodies (ACA), antibodies to the nonhistone chromosomal protein Scl-70 (anti-Scl-70), antibodies to RNA polymerase III (anti-RNAP III), antibodies to cytoplasmic antigen (anti-Ro), antibodies to cytoplasmic antigen SS-B (La) associated with RNA polymerase III (anti-La), antibodies against DNA (anti-DNA), antibodies to U1-, U2-, U4-ribonucleoproteins (anti-Sm (Smith)), antibodies to cardiolipin (AKL), anti-synthetase antibodies to cytoplasmic antigen (anti-Jo1). After 2 years of complex therapy, these patients were examined. Results: In patients of the study group, the clinical picture was dominated by inflammatory lesions of the joints and muscles, and skin manifestations were not very pronounced. Interstitial lung disease was detected in 47% of cases. Intersections with diseases (rheumatoid arthritis, systemic lupus erythematosus) were detected in 23% of cases and a combination with Sjögren’s syndrome in 21.3%. Other antibodies were often detected: RF (27%), anti-Ro (31%), anti-DNA (32%), rarely - anti-Sm (13%), ACCP (7%), anti-La (5%), ACA (7%), anti-Scl70 (4%), ACL (3%). Anti-Jo1 and anti-RNAP-III were not detected in any of the patients. In patients with systemic scleroderma, highly positive for anti-U1RNP (more than two upper limits of normal) compared with low positive, RF, anti-Ro, anti-DNA were significantly more common (p=0.00). In dynamics after 2 years, high titers of anti-U1RNP persisted in 65% of patients, while other autoantibodies were detected with the same frequency. In patients with an initially low titer of anti-U1RNP, their disappearance was noted. Conclusion: In patients with systemic scleroderma and overproduction of antiU1RNP, inflammatory musculoskeletal manifestations predominate and are often associated with Sjögren’s syndrome and overlap syndrome. High positivity for antiU1RNP was accompanied by a persistent increase in the levels of RF, anti-Ro, and anti-DNA. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None Declared. DOI: 10.1136/annrheumdis-2023-eular.2631 AB0870 ANTI-HMGCR AUTOANTIBODY LEVELS IN THE FOLLOW-UP OF STATIN-INDUCED IMMUNE-MEDIATED NECROTIZING MYOPATHY. MULTICENTRIC STUDY OF 24 PATIENTS Keywords: Myositis, Autoantibodies, Diagnostic Tests D. Martínez-López1, D. Prieto-Peña2, C. Corrales-Selaya2, P. Szczęsny3,4, A. Notarnicola5,6,7, M. López Hoyos8, R. Blanco2, I. E. Lundberg5,6,7, M. Dastmalchi5,6,7. 1Hospital de Sierrallana, Rheumatology, Torrelavega, Spain; 2 Hospital Universitario Marqués de Valdecilla, Rheumatology, Santander, Spain; 3National Institute of Geriatrics, Rheumatology and Rehabilitation, Rheumatology, Warsaw, Poland; 4Medical University of Warsaw, Neurology, Warsaw, Poland; 5Department of Medicine, Karolinska Institute, Rheumatology, Stockholm, Sweden; 6Karolinska University Hospital, Department of Gastro, Dermatology and Rheumatology, Stockholm, Sweden; 7Karolinska Institutet, Center for Molecular Medicine, Stockholm, Sweden; 8Hospital Universitario Marqués de Valdecilla, Immunology, Santander, Spain Image 1. MRI: SPAIR technique and fat suppression. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None Declared. DOI: 10.1136/annrheumdis-2023-eular.2384 AB0869 ANTI-NUCLEAR AUTOANTIBODIES IN ANTI-U1RNP POSITIVE SYSTEMIC SCLERODERMA PATIENTS Keywords: Systemic sclerosis S. Dahmani1, N. Zhuravleva2, T. Smirnova3, V. Diomidova3. 1Morocco,“Rahmani” Pharmacy, Casablanca, Morocco; 2Russia,“Chuvash State University named after I. N. Ulyanov”, Cheboksary, Russian Federation; 3“Chuvash State University named after I. N. Ulyanov”,“Chuvash State University named after I. N. Ulyanov”, Cheboksary, Russian Federation Background: In patients with systemic scleroderma (SSD) with overproduction of anti-U1ribonucleoprotein, there are features in the clinical picture and course of the disease. Background: Statin-induced immune-mediated necrotizing myopathy (IMNM) is associated with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies. It is characterized by elevated creatine kinase (CK) levels, and severe muscle weakness. Measuring disease activity is problematic, since it is challenging to differentiate it from damage. The utility of the quantitative analysis of anti-HMGCR autoantibodies during the follow-up has not been thoroughly studied. Objectives: To assess the usefulness of measuring the levels of anti-HMGCR autoantibodies in relation to response to treatment. Methods: We included patients all consecutive patients diagnosed with statin-induced IMNM according to the definition of the European Neuromuscular International Workshop 2016 (1) and positivity for anti-HMGCR autoantibodies in two centers from Spain and Sweden from January 2017 to November 2022. All patients were followed for at least 3 months to be included. Clinical data was extracted retrospectively from the patients’ clinical records. Remission was defined as no disease activity assessed by expert rheumatologists according to 2016 ACR/EULAR response criteria in myositis. Moderate and high disease activity was defined when physician global activity score was higher than 2 or 3 (on a Likert scale) respectively [2,3]. Anti-HMGCR autoantibodies level was measured at the time of diagnosis and at a variable period of time after treatment. Ann Rheum Dis: first published as 10.1136/annrheumdis-2023-eular.2384 on 30 May 2023. Downloaded from http://ard.bmj.com/ on February 17, 2024 by guest. Protected by copyright. 1648