Comparison of patients with axial PsA and patients with axSpA and concomitant psoriasis: an analysis of the German register RABBIT-SpA

BackgroundPsoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) show certain overlaps: A subset of patients with PsA can develop axial involvement (axial PsA, axPsA), while a subset of patients with axSpA presents with psoriasis (axSpA+pso). Treatment strategy for axPsA is mostly based on axSpA evidence.ObjectivesTo compare demographic and disease-specific parameters of axPsA and axSpA+pso.MethodsRABBIT-SpA is a prospective longitudinal cohort study. AxPsA was defined based on (1) clinical judgement by rheumatologists; (2) imaging (sacroiliitis according to modified New York criteria in radiographs or signs of active inflammation in MRI or syndesmophytes/ankylosis in radiographs or signs of active inflammation in spine MRI). axSpA was stratified into axSpA+pso and axSpA without pso.ResultsPsoriasis was documented in 181/1428 axSpA patients (13%). Of 1395 PsA patients, 359 (26%) showed axial involvement. 297 patients (21%) fulfilled the clinical definition and 196 (14%) the imaging definition of axial manifestation of PsA. AxSpA+pso differed from axPsA regardless whether clinical or imaging definition was used. axPsA patients were older, more often female and less often HLA-B27+. Peripheral manifestations were more often present in axPsA than in axSpA+pso, whereas uveitis and inflammatory bowel disease were more common in axSpA+pso. Burden of disease (patient global, pain, physician global) was similar among axPsA and axSpA+pso patients.ConclusionsAxPsA differs from axSpA+pso in its clinical manifestations, irrespective of whether axPsA is defined clinically or by imaging. These findings support the hypothesis that axSpA and PsA with axial involvement are distinct entities, so extrapolation of treatment data from randomised controlled trials in axSpA should be performed with caution

National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD

Objectives: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. Methods Using an online questionnaire (www.COVID19-rheuma.de.), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. Results Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males;63 females;1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. Conclusions: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic

Clinical health services research in breast cancer

Ein Ziel der klinischen Versorgungsforschung ist es, die Versorgungsrealität abzubilden und zu analysieren. In dieser kumulativen Habilitationsschrift werden sechs Arbeiten vorgestellt, die mit unterschiedlichen Methoden der Versorgungsforschung klinisch relevante Fragestellung der Therapie des Mammakarzinoms behandeln. Das metastasierte Mammakarzinom zeichnet sich durch einen extrem heterogenen Verlauf aus. Wir haben deshalb zunächst das Ziel gehabt, eine prognostische Einschätzung der Patienten zu dem Zeitpunkt der Sicherung einer Fernmetastasierung mit möglichst einfachen Faktoren zu ermöglichen. In der ersten Arbeit wurde hierzu mithilfe einer Cox- Regressionsanalyse ein Score entwickelt, mit dem die Patienten drei Risikogruppen zugeteilt werden können. Dieser sogenannte B2-Score ermöglicht eine sehr gute Diskriminierung der Patienten bzgl. ihrer Prognose. Als signifikante Faktoren wurden das metastasenfreie Intervall (MFI), die Lokalisation der Metastasen sowie der Hormonrezeptorstatus ermittelt. Die zweite Arbeit stellt ein erstes Anwendungsbeispiel unseres B2-Scores dar. Es wurde der umstrittenen Frage nachgegangen, ob das Gesamtüberleben der Patientinnen mit MBC sich im Verlauf der letzten Jahrzehnte verändert hat. Hier zeigt sich, dass das Gesamtüberleben ab Metastasierung in den Zeitkohorten 1980-94, 1995-99 und 2000-2009 unverändert blieb. Allerdings veränderte sich in den Kohorten die Risikostruktur der Patientinnen signifikant mit einer Zunahme der prognostisch negativen Faktoren in den jüngeren Zeitkohorten. Eine mögliche Erklärung hierfür könnte die effektivere adjuvante Behandlung sein, die quasi eine Negativ-Selektion der Patienten bewirkt, die trotz der konsequenten adjuvanten Therapie eine Metastasierung entwickeln. Wir schlussfolgern daraus, dass die gleichbleibende Prognose bei höherem Risiko als ein indirektes Zeichen einer Verbesserung der Therapie des MBC gewertet werden kann. Es ist weiterhin eine kontroverse Frage, für welche Patientin mit Hormonrezeptor positivem Mammakarzinom eine Chemotherapie zusätzlich zur endokrinen Therapie in der adjuvanten Situation notwendig ist und bei wem eine alleinige ET ausreichend ist. In der dritten Arbeit wurde deshalb der Einfluss der Höhe des ER auf das RFS und die Wirksamkeit einer adjuvanten Hormontherapie an einem Brustkrebsregister mit 3971 Patientinnen mit primärem Mammakarzinom untersucht. Wie zu erwarten, zeigte sich ein signifikanter Einfluss auf das rezidiv-freie Überleben mit der günstigsten Prognose für die ER hoch-exprimierenden und der schlechtesten Prognose für die ER-negativen Tumoren. In der Gruppe der ER-hoch exprimierenden Tumoren zeigte sich zudem kein Zusatznutzen für die Chemo-ET-Kombination im Vergleich zur alleinigen ET. Durch eine quantitative Betrachtung der Hormonrezeptoren im Gegensatz zur (üblichen) rein dichotomen Darstellung (positiv vs. negativ) konnte ein weiterer Hinweis für die Therapieentscheidung gewonnen werden. In der vierten und fünften hier vorgestellten Publikation werden seltene aber klinisch meist dramatisch verlaufende Metastasierungsformen des Mammakarzinoms analysiert. Die Evidenzlage solch seltener Verlaufsformen ist naturgemäß schlecht, klinische Studien sind meist nicht durchführbar, deshalb bilden Kasuistiken und Fallsammlungen häufig die einzige Evidenzquelle. Bei der Mammakarzinom-induzierten thrombotischen Mikroangiopathie handelt es sich um ein Syndrom, welches durch eine Thrombozytopenie in Kombination mit einer mikroangiopathischen hämolytischen Anämie gekennzeichnet ist. Unsere Fallserie zeigt weitere Hinweise auf eine Assoziation mit einer Knochenmarkkarzinose sowie auf die Wirksamkeit und Durchführbarkeit einer fraktionierten Polychemotherapie. Die Analyse der Patientinnen mit Meningeosis carcinomatosa verstärkte die Hinweise, dass eine systemische Therapie in dieser Situation indiziert ist. In der letzten der hier eingeschlossenen eigenen Arbeiten, werden internationale LL zur Behandlung des Mammakarzinoms, die eine hohe methodische Qualität aufweisen, miteinander hinsichtlich der Therapieempfehlungen der adjuvanten Situation verglichen. Es zeigten sich nur geringe Unterschiede zwischen den LL: Dies liegt unseres Erachtens v.a. daran, dass die LL sich auf die gleichen – meist internationalen – Therapiestudien beziehen. Zudem fielen gegenseitige LL-Zitate in den einzelnen LL auf. Eine kritische Hinterfragung der gängigen Praxis der Generierung von LL auf nationaler Ebene sollte deshalb erfolgen. Da die LL-Erstellung eine sehr zeit- und kostenintensive Aufgabe darstellt, sollte eine verstärkte internationale Kooperation (z. B. auf europäischer Ebene) erwogen werden.One of the main goals of clinical health services research is to analyze real world data in order to improve daily clinical care. Six different publications on breast cancer are included in this thesis. Metastatic breast cancer is extremely heterogeneous. In the first publication we developed a clinical score to judge the prognosis of patients at the onset of metastatic disease. We then showed an usage example of our risk score. The subject of the next publication is the influence of the quantity of hormone receptor expression on recurrence free survival in early breast cancer. We also analyzed very rare complications in breast cancer. In the last publication we compared different international clinical practice guidelines of breast cancer in regard of their treatment recommendations

Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID-19 hospitalisation in patients with inflammatory rheumatic and musculoskeletal diseases

Introduction Whether patients with inflammatory rheumatic and musculoskeletal diseases (RMD) are at higher risk to develop severe courses of COVID-19 has not been fully elucidated. Aim of this analysis was to describe patients with RMD according to their COVID-19 severity and to identify risk factors for hospitalisation.Methods Patients with RMD with PCR confirmed SARS-CoV-2 infection reported to the German COVID-19 registry from 30 March to 1 November 2020 were evaluated. Multivariable logistic regression was used to estimate ORs for hospitalisation due to COVID-19.Results Data from 468 patients with RMD with SARS-CoV-2 infection were reported. Most frequent diagnosis was rheumatoid arthritis, RA (48%). 29% of the patients were hospitalised, 5.5% needed ventilation. 19 patients died. Multivariable analysis showed that age >65 years (OR 2.24; 95% CI 1.12 to 4.47), but even more>75 years (OR 3.94; 95% CI 1.86 to 8.32), cardiovascular disease (CVD; OR 3.36; 95% CI 1.5 to 7.55), interstitial lung disease/chronic obstructive pulmonary disease (ILD/COPD) (OR 2.79; 95% CI 1.2 to 6.49), chronic kidney disease (OR 2.96; 95% CI 1.16 to 7.5), moderate/high RMD disease activity (OR 1.96; 95% CI 1.02 to 3.76) and treatment with glucocorticoids (GCs) in dosages >5 mg/day (OR 3.67; 95% CI 1.49 to 9.05) were associated with higher odds of hospitalisation. Spondyloarthritis patients showed a smaller risk of hospitalisation compared with RA (OR 0.46; 95% CI 0.23 to 0.91).Conclusion Age was a major risk factor for hospitalisation as well as comorbidities such as CVD, ILD/COPD, chronic kidney disease and current or prior treatment with GCs. Moderate to high RMD disease activity was also an independent risk factor for hospitalisation, underlining the importance of continuing adequate RMD treatment during the pandemic

No difference in clinical parameters and drug retention in PsA patients receiving b/tsDMARD monotherapy versus combination with methotrexate: data from the RABBIT-SpA registry

Background The potential benefit of methotrexate (MTX) in combination with biologic (b) and targeted synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) is still a matter of debate.Objectives To compare clinical and patient reported characteristics as well as drug retention rates in PsA patients receiving b/tsDMARD monotherapy or in combination with MTX.Methods RABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients. In this analysis, PsA patients were stratified into two groups: starting b/tsDMARD as monotherapy or in combination with MTX. Treatment retention was compared by drug survival analysis.Results 69% of the patients (n=900) started b/tsDMARD as monotherapy while 31% were treated in combination with MTX (n=405). At baseline, clinical domains like skin, nail and joint affection, dactylitis, enthesitis and axial involvement were similar between the groups. Only the patients’ satisfaction concerning tolerability of the previous treatment was significantly better in the combination group at treatment start. Drug retention rates did not differ between the groups (p=0.4). At 6/12 months, 66%/48% of patients in monotherapy and 67%/48% in the combination group were still on their original treatment.Conclusions We did not identify any clinical parameters with notable influence on the choice of b/tsDMARD mono or MTX-combination therapy in PsA. Drug retention rates are similar between mono and combination therapy. It seems that the decision to continue MTX at initiation of b/tsDMARDs is mostly based on the subjective tolerability of MTX treatment

Characteristics associated with poor COVID-19 outcomes in people with psoriasis, psoriatic arthritis and axial spondyloarthritis:data from the COVID-19 PsoProtect and Global Rheumatology Alliance physician-reported registries

Funding The study received support from the American College of Rheumatology (ACR) and European Alliance of Associations for Rheumatology (EULAR).OBJECTIVES: To investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression. RESULTS: Of 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25-2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39-2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42-0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19. CONCLUSION: Older age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.publishersversionepub_ahead_of_prin

Characteristics and outcomes of SARS-CoV-2 breakthrough infections among double-vaccinated and triple-vaccinated patients with inflammatory rheumatic diseases

Objective To analyse the clinical profile of SARS-CoV-2 breakthrough infections in at least double-vaccinated patients with inflammatory rheumatic diseases (IRDs).Methods Data from the physician-reported German COVID-19-IRD registry collected between February 2021 and July 2022 were analysed. SARS-CoV-2 cases were stratified according to patients’ vaccination status as being not vaccinated, double-vaccinated or triple-vaccinated prior to SARS-CoV-2 infection and descriptively compared. Independent associations between demographic and disease features and outcome of breakthrough infections were estimated by multivariable logistic regression.Results In total, 2314 cases were included in the analysis (unvaccinated n=923, double-vaccinated n=551, triple-vaccinated n=803, quadruple-vaccinated n=37). SARS-CoV-2 infections occurred after a median of 151 (range 14–347) days in patients being double-vaccinated, and after 88 (range 14–270) days in those with a third vaccination. Hospitalisation was required in 15% of unvaccinated, 8% of double-vaccinated and 3% of triple-vaccinated/quadruple-vaccinated patients (p<0.001). Mortality was 2% in unvaccinated, 1.8% in the double-vaccinated and 0.6% in triple-vaccinated patients. Compared with unvaccinated patients, double-vaccinated (OR 0.43, 95% CI 0.29 to 0.62) and triple-vaccinated (OR 0.13, 95% CI 0.08 to 0.21) patients showed a significant lower risk of COVID-19-related hospitalisation. Using multivariable analysis, the third vaccination was significantly associated with a lower risk for COVID-19-related death (OR 0.26; 95% CI 0.01 to 0.73).Conclusions Our cross-sectional data of COVID-19 infections in patients with IRD showed a significant reduction of hospitalisation due to infection in double-vaccinated or triple-vaccinated patients compared with those without vaccination and even a significant reduction of COVID-19-related deaths in triple-vaccinated patients. These data strongly support the beneficial effect of COVID-19 vaccination in patients with IRD.Trial registration number EuDRACT 2020-001958-21