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Background and Objectives: Ocular myasthenia gravis (OMG) causes disabling ocular symptoms of ptosis and diplopia, but a validated disease-specific patient-reported outcome measure (PROM) has not been reported. We sought to validate a novel PROM for OMG, OMG Rating Scale Questionnaire (OMGRate-q), as a measure of visual functioning to support patient-centered care., Methods: This was a prospective study of patients aged 18 years and older with OMG receiving care at 3 medical centers (January 2022-October 2023). The 10-item OMGRate-q was administered, and response data were analyzed using exploratory factor analysis followed by Andrich rating scale model fitting. Poorly fitting items were eliminated, and the model was refit to produce the final items, item locations, and thresholds. Latent scores (theta) were estimated, test-retest reliability was established with repeat measures, and correlation with other myasthenia gravis PROMs was measured., Results: Of the 134 patients included in the study, 45 (33.6%) were women, 99 (73.9%) were White, and the median age (interquartile range [IQR]) was 64.6 years (52.6-73.9 years). A ptosis-related item showed significant item-trait deviation ( p < 0.001) and was kept as a separate factor from the remaining diplopia-related items. After excluding this item, there were no misfitting items. Theta estimation for the diplopia scale ranged from -3.47 to 5.51 with median = -0.53 (IQR -2.33, 0.72). Test-retest reliability of the OMGRate-q diplopia subscale was high (intraclass correlation coefficient = 0.95 [95% CI 0.90-0.98]) and of the ptosis item was good (weighted κ = 0.56). No significant differences were observed in OMGRate-q diplopia subscale scores or the ptosis item between the 3 sites (diplopia p = 0.44; ptosis p = 0.32). OMGRate-q scores were moderately to highly correlated with the Myasthenia Gravis Quality of Life 15 questionnaire (n = 122; diplopia: r = 0.68, p < 0.001; ptosis: r = 0.48, p < 0.001) and Myasthenia Gravis Impairment Index (n = 130; diplopia: r = 0.76, p < 0.001; ptosis: r = 0.77, p < 0.001). OMGRate-q length was acceptable to most participants (125/130 [96.2%]), and the questionnaire was completed in 80.7 (±45.2) seconds., Discussion: The OMGRate-q is a valid and reliable disease-specific PROM for OMG that may be used to facilitate patient-centered research and care. However, the OMGRate-q emphasizes the impact of diplopia on visual functioning with a single separate item measuring ptosis. Future studies are needed to determine OMGRate-q responsiveness to disease-state changes and how to add measures of ptosis to this scale or whether a separate measure is needed.

Competing Interests: Competing interests: D.P. has received research support from AbbVie, Eli Lilly, MSD, Novartis, Pfizer, consulting fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer and UCB, and speaker fees from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer and UCB, and is a member of the Assessment of SpondyloArthritis International Society executive committee and of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis steering committee.

Objective: Axial spondyloarthritis (axSpA) is an inflammatory disease in which overactive interleukin (IL)-17A-producing cells are implicated in a central role. Therapeutically, biologics that target IL-17A, such as secukinumab, have demonstrated improved clinical outcomes. Despite this translational success, there is a gap in understanding why some patients with axSpA do not respond to IL-17A-blocking therapy. Our study aims to discriminate immune profiles between secukinumab responders (SEC-R) and nonresponders (SEC-NR)., Methods: Peripheral blood mononuclear cells were collected from 30 patients with axSpA before and 24 weeks after secukinumab treatment. Frequency of CD4+ subsets were compared between SEC-R and SEC-NR using flow cytometry. Mature CD45RO+CD45RA-CD4+ T cells were fluorescent-activated cell sorting sorted, and RNA was measured using NanoString analysis., Results: SEC-NR had an increased frequency of IL-17A-producing RORγt+CD4+ T cells compared to healthy controls before secukinumab treatment (P < 0.01). SEC-NR had a significant increase of CXCR3+ CD4+ T cells before secukinumab treatment compared to SEC-R (P < 0.01). Differentially expressed gene analysis revealed up-regulation of type 1 interferon (IFN)-regulated genes in SEC-NR patients compared to SEC-R patients after receiving the biologic. SEC-R patients had an up-regulated cytotoxic CD4+ T cell gene signature before receiving secukinumab treatment compared to SEC-NR patients., Conclusion: The increased frequency of IL-17A-producing cells in SEC-NR patients suggests a larger inflammatory burden than SEC-R patients. With treatment, SEC-NR patients have a more pronounced type 1 IFN signature than SEC-R patients, suggesting a mechanism contributing to this larger inflammatory burden. The results point toward more immune heterogeneity in axSpA than has been recognized and highlights the need for precision therapeutics in this disease., (© 2024 American College of Rheumatology.)