Methotrexate (MTX), an antifolate drug, is the first-line disease-modifying agent for the treatment of rheumatoid arthritis (RA) worldwide. MTX has excellent long-term efficacy, tolerability and safety. Early initiation of MTX in patients with RA controls joint destruction and slows progression of disease. However, the clinical response to MTX and frequency of adverse effects from the drug exhibit marked interpatient variability. Over the past decade, there has been a quest to identify genetic markers that reliably predict MTX efficacy and toxicity and help optimize MTX therapy in RA; that is, the field of MTX pharmacogenetics. This review will summarize key pharmacogenetic studies examining SNPs in the genes encoding enzymes in the MTX cellular pathway and their association with MTX response in RA. As evident from this review, MTX pharmacogenetics in RA remains a muddled field, mostly due to inconsistent results from several small underpowered studies.
Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vs 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset.Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2.
BackgroundThe application and appropriate use of imaging-based scoring instruments is usually based on passive learning from published manuscripts while real-time interaction with instrument developers is often non-feasible. Moreover, most instruments lack knowledge transfer tools that would facilitate attainment of pre-specified performance targets for reader reliability.Objectives1. To develop a web-based calibration module for the SPARCC MRI SIJ Inflammation Score based on consensus scores from these instrument developers, experiential game psychology, and real-time iterative feedback. 2. To test the feasibility and attainment of pre-specified performance targets for reader reliability.MethodsThe scoring of inflammatory lesions of the SIJ on MRI using the SPARCC method is based on SIJ quadrants and the calibration module is comprised of 50 DICOM cases, each with scans from baseline and 12 weeks after the start of TNF inhibitor therapy. Scans are scored blinded-to-time-point. Continuous visual real-time feedback regarding concordance/discordance of scoring per SIJ quadrant with expert readers is provided by a color-coding scheme. Reliability is additionally assessed by real-time intra-class correlation coefficient with the first ICC data being provided after 20 cases. Accreditation for SPARCC BME score is achieved with status and change score ICC of >0.8 and>0.7 and is based on the final 20 cases. 26 readers scored the SPARCC BME module (7 rheumatology fellows, 2 chiropracters, 1 undergraduate, 8 rheumatologists, 8 radiologists) with 21 having no prior experience. Feasibility was assessed by 8-item survey.ResultsThe majority of readers achieved accreditation for SPARCC BME score on the basis of sufficient reliability with instrument developers for both status and change scores, irrespective of prior experience (table 1). All readers who completed the module a second time, 6 months after the first exposure, achieved accreditation for SPARCC BME score. All readers rated the modules as easy and intuitive with average time for reading each case for SPARCC BME being 8 min.Abstract FRI0597 – Table 1*Proficiency targets for reader reliability**7 rheumatology fellows, 2 chiropractors, 1 undergraduateConclusionsExperiential web-based learning is an effective and feasible calibration tool to achieve proficiency targets in the scoring of MRI scans for SIJ inflammatory lesions.Disclosure of InterestW. Maksymowych Shareholder of: CaRE Arthritis, S. Krabbe: None declared, D. Biko: None declared, P. Weiss: None declared, M. Maksymowych: None declared, J. Cheah: None declared, G. Kröber: None declared, U. Weber: None declared, K. Danebod: None declared, P. Bird: None declared, P. Chiowchanwisawakit: None declared, J. Moeller: None declared, M. Francavilla: None declared, J. Stimec: None declared, T. Kogay: None declared, V. Zubler: None declared, M. Battish: None declared, N. Winn: None declared, D. Rumsey: None declared, R. Guglielmi: None declared, S. Pedersen: None declared, H. Boutrup: None declared, S. Shafer: None declare...
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