Michael J. Nissen

Description:Objective: In patients with axial spondyloarthritis (axSpA) initiating secukinumab (SEC), we aimed to identify baseline (treatment start) predictors of achieving low disease activity (LDA) after 6 months, as measured by the Axial Spondyloarthritis Disease Activity Score using C-reactive protein (ASDAS-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), as well as treatment continuation after 12 months. Methods: From 11 European registries, patients with axSpA who initiated SEC treatment in routine care, with available data on 6-month ASDAS-CRP and BASDAI assessments were included. Logistic regression analyses on multiply imputed baseline data were performed; potential baseline predictors included demographic, diagnosis, lifestyle, clinical, and patient-reported variables. Results: In a pooled cohort of 1174 patients with axSpA, 5 of 19 potential assessed variables were mutually predictive for achieving LDA by ASDAS-CRP and BASDAI: higher physician global assessment score, noncurrent smoking, lack of prior exposure to biologic/targeted synthetic disease-modifying antirheumatic drugs, and lower Health Assessment Questionnaire scores and BASDAI scores. Moreover, radiographic axSpA and CRP ≤ 10 mg/L were associated with achieving ASDAS-CRP LDA, and HLA-B27 positivity and history of psoriasis with achieving BASDAI LDA, whereas earlier time of secukinumab initiation (2015-2017) was associated with treatment continuation. Conclusions: In this European real-world study of patients with axSpA initiating SEC, predictors of achieving LDA by ASDAS-CRP and BASDAI at 6 months and remaining on treatment at 12 months included both clinical, patient-reported, and lifestyle factors, underscoring the complex mechanisms of real-world drug effectiveness.

Description:Clinical progression and medium-long term morbidity from myocarditis following mRNA COVID-19 vaccinations remains an important but undefined public health concern. We conducted prospective follow-up of individuals with either confirmed or probable myocarditis following monovalent Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccination between 21 April 2021 and 5 July 2022 in Australia. Of 256 individuals who consented to follow up, mostly males following a second dose, 60% (133/221) had ongoing symptoms at 3-6 months and 35% (81/231) at 12-18 months. Self-reported ongoing exercise restrictions, medication requirements, and hospital re-presentations were associated with ongoing symptoms, as was a lower self-reported health status and quality of life. Clinical severity remained mild, with low hospitalisation rates and no deaths in the follow-up period and health-related quality of life improved over time. These findings support ongoing use of mRNA COVID-19 vaccines in at-risk individuals to prevent disease caused by SARS-CoV-2 infection.

Description:Objective: Anti-CD74 antibodies (Abs) have been proposed as a diagnostic biomarker in axial spondyloarthritis (axSpA). The aims of this study were to evaluate the association of these Abs with disease activity parameters in axSpA and to assess their predictive value for tumour necrosis factor inhibitor (TNFi) treatment effectiveness. Methods: Patients diagnosed with axSpA in the Swiss Clinical Quality Management registry with available biosamples and a measurement of IgA anti-CD74 Abs were included in this cohort study. We used a cut-off of 15 U/ml to define anti-CD74 Abs elevation. Associations of important disease characteristics with anti-CD4 Abs elevation and anti-CD74 Abs levels were evaluated using logistic and linear regression, respectively. For patients with an available biosample before TNFi initiation, we evaluated drug retention and estimated the hazard ratio of treatment discontinuation depending on anti-CD74 Abs elevation. Results: Elevated IgA anti-CD74 Abs were found in 383/722 (53%) patients with axSpA and were significantly associated with older age, male sex, and elevated C-reactive protein (CRP). Among 310 patients starting TNFi treatment, no significant difference in drug retention was found between patients with and without elevated anti-CD74 Abs (HR 0.91, 95% CI 0.66 to 1.25). An increased Bath Ankylosing Spondylitis Disease Activity Index was found to be associated with a reduced TNFi retention whereas an elevated CRP was associated with a prolonged retention. Conclusions: Although elevated IgA anti-CD74 Abs are associated with CRP elevation, we could not demonstrate an additional value of this biomarker for predicting response to treatment with TNFi beyond CRP measurement.

Description:Background: To investigate a patient-level single imputation approach for patient reported outcomes (PROs) that express similar contents or associated PROs, where a PRO whose value is missing at a particular timepoint is substituted by another PRO whose value is available at the same timepoint. Methods: We performed a simulation study on registry-based spondyloarthritis data to explore the potential interchangeability between the patient pain (PPA) and fatigue (PFA) assessment scores and relevant Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) individual questions, and between PPA, PFA and patient global assessment (PGA). Performance was assessed per imputation method in terms of relative bias and coverage. Sample size, level of missingness and missing data pattern were included as parameters in the simulations. Results: All applied scenarios to interchange PPA with BASDAI question 2 (axial pain), BASDAI question 3 (peripheral joint pain/swelling) or their average failed. Interchangeability between PFA and BASDAI question 1 (fatigue/tiredness) was acceptable for partially (up to 50%) missing data. When interchanging patient assessment scores (PPA, PFA and PGA), we observed inconsistent results in terms of performance. The performance of the applied methods depended on the sample size and the level of missingness, but not heavily on the underlying missing data pattern. Conclusions: Interchanging PFA and the BASDAI fatigue question was justified for partially missing data, while interchangeability between PPA, PFA and PGA, and between PPA and the BASDAI pain questions was not advised. Our findings suggest that registering patient assessment scores and BASDAI questions is recommended.

Description:Background: Studies on national policies for biologics are warranted. Objective: To map and compare national healthcare set-ups for prescription, start, switch, tapering, and discontinuation of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with psoriatic arthritis and axial spondyloarthritis across Europe, and assess the healthcare set-ups in relation to countries' socio-economic status. Methods: An electronic survey was developed to collect and compare information on national healthcare systems. The relationship between the cumulative score of biologic/targeted synthetic DMARD regulations, socioeconomic indices, and biologic originator costs were assessed by linear regression. Results: National healthcare set-ups differed considerably across the 15 countries, with significantly fewer regulations with increasing socioeconomic status measured by GDP/current health expenditure/human development index, and with increasing biologic originator costs. In most countries, the biologic/targeted synthetic DMARD prescribing doctor was required to adhere to country and/or hospital recommendations, and about a third of countries had a national/regional tender process. Prescription regulations for biologic/targeted synthetic DMARDs, including pre-treatment and disease activity requirements, varied substantially. Approximately a third of countries had criteria for discontinuation and tapering, whereas only few had for switching. Notably, two countries disallowed biologic/targeted synthetic DMARD retrials, and one imposed limit on the maximum number of biologic/targeted synthetic DMARDs permitted. Conclusions: The findings highlight substantial variability in healthcare set-ups for biologic/targeted synthetic DMARD use in psoriatic arthritis and axial spondyloarthritis across Europe and their association with socioeconomic status and drug costs. These insights provide a basis for rheumatology societies, policymakers, and stakeholders to evaluate and potentially optimize healthcare policies.