140 research outputs found
Characteristics and outcomes of SARS-CoV-2 breakthrough infections among double-vaccinated and triple-vaccinated patients with inflammatory rheumatic diseases
No full textObjective 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.German Society for Rheumatolog
Biologics registers in rheumatology as modern instruments of pharmacovigilance
No full textDie an randomisierten klinischen (Zulassungs-)studien teilnehmenden Patienten werden nach strengen Ein- und Ausschlusskriterien selektiert und bilden somit nur einen kleinen Teil der im klinischen Alltag behandelten Patienten ab. Ziel dieser Habilitationsschrift war es, anhand der Daten des RABBIT Registers, die Bedeutung sogenannter Biologikaregister als Instrumente der Pharmakovigilanz darzulegen, sowie deren Schwächen und Limitationen aufzuzeigen.
In den insgesamt sieben Arbeiten wird das Risiko unterschiedlicher unerwünschter Ereignisse unter verschiedenen Therapien verglichen. Es wird das erhöhte Risiko für das Auftreten eines Herpes zoster vor allem unter Therapie mit den monoklonalen TNF-Antikörpern Adalimumab und Infliximab im Vergleich zur konventionellen Standardtherapie (csDMARD) vorgestellt und in einer weiteren Arbeit das ebenfalls signifikant erhöhte Risiko für schwerwiegende bakterielle Infektionen unter Biologika (bDMARDs), das aber im Kontext mit weiteren konkurrierenden Risiken gesehen werden muss. Hinsichtlich der Entwicklung einer Sepsis oder Mortalität zeigte sich ein signifikant positiver Effekt, der mit bDMARD Therapie assoziiert war. Es wird das erhöhte Risiko für Perforationen des unteren Darmtraktes unter Tocilizumab aufgezeigt, sowie die unter dieser Therapie untypische klinische Symptomatik beschrieben. Bei der Untersuchung des Risikos für inzidente und rekurrente Malignome unter bDMARDs zeigte sich kein Unterschied im Vergleich zur konventionellen Standardtherapie. In den beiden letzten vorgestellten Arbeiten, die das Auftreten des Myokardinfarkts und vorzeitige Mortalität untersuchen, wird der signifikante Einfluss hoher inflammatorischer Aktivität auf das Auftreten dieser Ereignisse verdeutlicht.
Im Rahmen dieser Arbeit werden die Schwierigkeiten aufgezeigt, die sich bei der Auswertung von Längsschnittdaten und Beobachtungsstudien ergeben, aber auch mögliche Lösungsansätze diskutiert. Die Ergebnisse zeigen ein insgesamt positives Sicherheitsprofil der bislang zur Behandlung der rheumatoiden Arthritis eingesetzten bDMARD Therapien. Durch die adäquate Anwendung geeigneter statistischer Methoden war es möglich, über die ursprünglich im Fokus stehenden Risiken der medikamentösen Therapie hinaus, auch weitere mit dem Auftreten unerwünschter Ereignisse assoziierte Risikofaktoren zu identifizieren.Patients participating in randomized clinical (approval) studies are selected according to strict inclusion and exclusion criteria and thus represent only a small proportion of the patients treated in everyday practice. The aim of this thesis was to use the data of the RABBIT register to illustrate the importance of biologics registers as instruments of pharmacovigilance as well as to discuss their weaknesses and limitations.
Seven papers in this thesis compare the risk of distinct adverse events under different therapies. The increased risk for the occurrence of herpes zoster especially under treatment with monoclonal TNF-antibodies (Adalimumab and Infliximab) compared to the conventional standard therapy (csDMARD) is presented. In a further work the significantly increased risk for serious bacterial infections under biologics, which however must be seen in the context of further concurrent risks, is also presented. With regard to the development of sepsis or mortality, a significantly positive effect associated with bDMARD therapy was found. The increased risk for perforations of the lower intestinal tract under tocilizumab is presented, as well as the clinical symptoms atypical of this therapy. The examination of the risk for incident/recurrent malignancies under bDMARDs showed no difference compared to the conventional standard therapy. The two last papers of this thesis examine the risks for myocardial infarction and premature mortality. They show the significant influence of high inflammatory activity on the occurrence of these events.
In this work, difficulties with the assessment and interpretation of longitudinal data and observational studies are pointed out and different strategies how to deal with those limitations are discussed. The results show an overall positive safety profile of the bDMARD therapies used to date for the treatment of rheumatoid arthritis. Through the adequate application of suitable statistical methods, it was possible to identify risk factors associated with the occurrence of adverse events in addition to the risks of drug treatment, which were originally the focus of attention
Interstitial lung disease in rheumatoid arthritis: incidence, prevalence and related drug prescriptions between 2007 and 2020
No full textOBJECTIVE: To investigate prevalence, incidence and medication of interstitial lung disease (ILD) among German individuals with rheumatoid arthritis (RA). METHODS: Nationwide BARMER claims data from 2007 to 2020 were used. RA-ILD was identified by diagnosis codes, prescription of disease-modifying antirheumatic drugs (DMARDs) and lung diagnostics. ILD was assigned as incident or prevalent relative to the year of the first diagnosis. We identified prescriptions of glucocorticoids, conventional synthetic (cs), biological (b) and targeted synthetic (ts)DMARDs, antifibrotics and rheumatology and/or pulmonology care. RESULTS: Among all persons with RA (40 686 in 2007 to 85 175 in 2020), 1.7%–2.2%/year had ILD with a slight decline since 2013. Incident ILD was 0.13%–0.21% per year and remained stable over time. ILD was more common in seropositive RA, in men and in the elderly (mean age 72 years in 2020). Glucocorticoids (84% to 68%), csDMARD (83% to 55%) and non-steroidal anti-inflammatory drug use (62% to 38%) declined, while bDMARDs (16% to 24%) rose. In 2020, 7% received tsDMARDs, 3% antifibrotics, 44% analgesics and 30% opioids. DMARD therapy was more common if a rheumatologist was involved and antifibrotics if a pulmonologist was involved. Opioid use was highest if no specialist was involved (39%) but also common in rheumatology care (32%) and less frequent in pulmonology care (21%). CONCLUSIONS: RA-ILD is rare and mainly affects elderly persons. No trend in incidence was observed but treatment strategies have enlarged. Specialist care is necessary to provide disease-specific therapies. The continuing high analgesic and opioid demand shows unmet needs in these patients
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