POS0071 IS ANTI-NXP2 AUTOANTIBODY A RISK FACTOR FOR CALCINOSIS AND POOR OUTCOME IN JUVENILE DERMATOMYOSITIS PATIENTS?
Authors: N. Toplak, P. P. Chavan, S. Rosina, T. Dallos, R. Semo Oz, C. Aguiar, R. Khubchandani, A. Ravelli, A. Patwardhan
Journal: Annals of the Rheumatic Diseases (2021)

Background: It has been published that the presence of NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. Objectives: To investigate the incidence of calcinosis and response to the treatment in NXP2 positive JDM patients with calcinosis. Methods: The study design is a retrospective, multinational, multicenter study. Data on gender, race, age at disease onset and age at disease diagnosis, age at inclusion in the study, clinical presentation, muscle function tests, laboratory results, imaging, data on treatment and outcome of disease were collected Results: we collected 26 patients (19 F, 7 M) with JDM and positive NXP2 antibodies. Fourteen patients were white, eight asian, three black and one Hispanic ethnicity. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5- 27 months). Patients were divided in two groups (A and B) based on the presence of calcinosis. Eleven patients (42%) developed calcinosis (group A) in the course of the disease, 10 females and 1 male. Four patients already had calcinosis at presentation, 1 developed after 4 months, and 6 developed calcinosis later in disease course (median 2 years, range 0,8- 7,8). Four patients developed lipodystrophy in group A (1 in group B). In group A, 3 patients developed skin ulcerations (1 in group B), 2 patients had polyarthritis (1 in group B), 2 patients had gut involvement (1 in group B) and 1 patient had lung involvement (2 in group B). The mean age at disease presentation (5.2 / 7.5 y) and mean CK level (1548.6 / 1811.6 U/L) were lower in group A. The platelet count (306.5 / 258 10 9 /L), and mean values of AST (111.4 / 103.8 U/L), ALT (72.2 / 50.8 U/L), LDH (1048.3 / 808 IU/L), and IgG (11.8 / 9.9 g/L) were higher in group A. However, the differences were not statistically significant. ANA antibodies were positive in 9/11 in group A and 12/15 in group B. One patient in group A was also positive for anti-MDA5 antibody. The data on muscle strength measurement (MMT/CMAS) were available only in a few patients. Treatments used for patients with calcinosis includes, methotrexate and glucocorticosteroids (GCS) (all patients), hydroxychloroquine (9), IVIG (7), cyclosporine (4), bisphosphonate (4), MMF (5), rituximab (4), cyclophosphamide (1), abatacept (1) and TNF alpha blocker (1). Disease outcome (by evaluation of the treating physician) was excellent in 4, good in 2, stable in 2 and poor in 3 patients. None of the patients from group B had a poor disease outcome. Patients with excellent disease outcomes from group A were treated with GCS and methotrexate (4), hydroxychloroquine (3), IVIG (1) and cyclosporine (1). Out of two patients who had good outcomes, one was additionally treated with MMF, bisphosphonates and rituximab and the second was treated with cyclophosphamide and rituximab. One patient with calcinosis at the presentation (age 4 years) was treated also with anti-TNF alpha therapy which not only stopped progression but partially dissolved the calcinosis. However, after 2 years of anti-TNF alpha therapy the calcinosis start to progress and the therapy was changed to MMF and rituximab, which stopped the progression of calcinosis. Conclusion: Our preliminary results showed that calcinosis occurred in 42% of NXP2 positive JDM patients. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and in one case, for limited time of 2 years, anti-TNF alpha agent, were used successfully. References: [1]Chung MP, Richardson C, Kirakossian D, Orandi AB, Saketkoo LA, et al. Calcinosis biomarkers in adult and juvenile dermatomyositis. Autoimmun Rev 2020; 19(6):102533. Disclosure of Interests: Natasa Toplak: None declared, Pallavi Pimpale Chavan: None declared, Silvia Rosina: None declared, Tomas Dallos Consultant of: Abbvie, Novartis, Rotem Semo Oz: None declared, Cassyanne Aguiar: None declared, Raju Khubchandani: None declared, Angelo Ravelli: None declared, Anjali Patwardhan: None declared.