OP0042 NORMAL CREATINE KINASE IN IDIOPATHIC INFLAMMATORY MYOPATHIES-DISEASE CHARACTERISTICS AND OUTCOMES
Authors: S. Keret, L. Kaly, T. Chandra, R. Lomanto Silva, E. Gkiaouraki, N. Pongtarakulpanit, S. Sriram, S. Moghadam-Kia, C. V. Oddis, R. Aggarwal
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Creatine kinase (CK) is considered an important biomarker for the diagnosis and monitoring of Idiopathic Inflammatory Myopathies (IIM). However, in some cases, CK levels might exhibit only minor elevation or remain within the normal range, even in the setting of active muscle disease. The data regarding normal CK in IIM are limited. <h3>Objectives:</h3> To characterize IIM patients with normal CK levels, and to investigate the CK level in association with demographic and clinical phenotypes as well as with various aspects of disease activity and outcomes. <h3>Methods:</h3> Data were collected from the Rituximab in Myositis (RIM) study, a large prospective multicenter, randomized, double-blind, placebo-controlled trial. Enrolled participants included patients with dermatomyositis (DM) or polymyositis (PM) with refractory disease despite the use of glucocorticoids and at least one other immunosuppressive treatment. Data were collected on all core set measures (CSMs), including CK, manual muscle testing (MMT), physician-global disease activity (physician-global) and patient-global disease activity (patient-global), extra-muscular disease activity, and Health Assessment Questionnaire- Disability Index (HAQ-DI). These CSMs were recorded at baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, and 44. For standardization purposes, CK levels were expressed as a multiple of their lab upper limits of normal [ULN]). "Normal" CK including near normal CK was defined based on a serum level within twice the ULN as per the laboratory reference range, whereas "elevated" CK was determined by levels surpassing this threshold. "Definition of improvement" (DOI) was based on the International Myositis Assessment and Clinical Studies Group (IMACS) preliminary validated response criterion of a ≥ 20% improvement in 3 of any 6 CSMs, with no more than 2 worsening by ≥ 25%. <h3>Results:</h3> 143 patients were analyzed, including 67 patients with normal/near normal CK and 76 with an elevated CK. The former group had a higher prevalence of Caucasians (84% vs. 59%, p=0.001), females (84% vs. 67%, p=0.023), and DM (64% vs. 37%, p=0.001), while the latter group exhibited a tendency toward increased age, although this trend did not achieve statistical significance (p=0.056). At baseline, the elevated CK group had a worse (lower) MMT score (101± 20 vs. 108±16, p=0.021), more active muscle disease (VAS 5.77± 2.01 vs. 4.28± 1.90, p&lt;0.001), and less extra-muscular global disease activity (VAS 2.38± 2.11 vs. 3.35±1.70, p=0.001). Disease activity (both patient and physician assessed) was higher in the elevated CK group (p=0.024 and p&lt;0.001, respectively). However, the HAQ-DI, patient-global disease damage assessment, and achievement of DOI, were similar between groups (<b>Table 1</b>). At baseline, in the elevated CK group, there was a clear association between CK levels and physician-global assessment (p=0.018) as well as muscle disease activity (p=0.005). Conversely, in patients with normal CK levels, no associations were observed between CK levels and other CSMs at baseline. Employing a linear mixed model with adjustment for age, sex, and race, CK levels exhibited a significant correlation (p&lt;0.001) during the follow-up period with various parameters, including MMT, patient-global, physician-global, muscle disease activity, and extra-muscular disease activity. This correlation was strong regardless of baseline CK status (normal vs. elevated) or myositis sub-type (DM vs. PM) (<b>Figure 1</b>). <h3>Conclusion:</h3> Normal CK levels are frequently noted in IIM, and do not exclude the presence of active muscle disease. Patients with normal CK levels exhibit distinct demographic and clinical characteristics. CK levels demonstrate a strong longitudinal correlation with other CSMs, irrespective of baseline CK levels or myositis sub-type, highlighting the importance of CK as a biomarker for monitoring disease activity in all IIM patients. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Shiri Keret: None declared, Lisa Kaly: None declared, Tanya Chandra: None declared, Raisa Lomanto Silva: None declared, Eugenia Gkiaouraki: None declared, Nantakarn Pongtarakulpanit: None declared, Shreya Sriram: None declared, Siamak Moghadam-Kia: None declared, Chester V Oddis: None declared, Rohit Aggarwal 1. Actigraph: Consultant, 2. Alexion: Consultant, 3. ANI Pharmaceuticals: Consultant, 4. Argenx: Consultant, 5. AstraZeneca: Consultant, 6. Boehringer-Ingelheim: Consultant, 7. Bristol Myers-Squibb: Consultant, 8. CabalettaBio: Consultant, 9. Capella Bioscience: Consultant, 10. Corbus: Consultant, 11. CSL Behring: Consultant, 12. EMD Serono: Consultant, 13. Galapagos: Consultant, 14. Horizon Therapeutics: Consultant, 15. I-Cell: Consultant, 16. Janssen: Consultant, 17. Kezar: Consultant, 18. Kyverna: Consultant, 19. Merck: Consultant, 20. Novartis: Consultant, 21. Nuvig Therapeutics: Consultant, 22. Octapharma: Consultant, 23. Pfizer: Consultant, 24. Regeneron: Consultant, 25. Roivant: Consultant, 26. Sanofi: Consultant, 27. Teva: Consultant, 28. Artsome: Consultant, 29. Capstanx: Consultant, 30. Manta: Consultant, 1. Boehringer Ingelheim (BI): 2. Bristol Myers-Squibb, 3. EMD Serono, 4. Janssen, 5. Mallinckrodt, 6. Pfizer, 7. Q32.