Infictieuze complicaties van biologicals bij de behandeling van reumatoïde artritis

De behandeling van reumatoïde artritis heeft een revolutie ondergaan sinds de introductie van biologicals. Een bekende complicatie van deze middelen is een verhoging van het risico op ernstige infecties, wat in verschillende mate bij de verschillende klassen voorkomt. Doordat TNF-alfaremmers onder andere granuloomvorming tegengaan, vormen ze een belangrijke risicofactor voor de reactivatie van latente tuberculose (tbc). Tocilizumab remt interleukine-6. Abatacept remt de T-celcostimulatie, waardoor een robuuste T-celrespons wordt tegengegaan. Rituximab, een monoclonaal dat CD20-positieve B-cellen depleteert, heeft als belangrijk risico reactivatie van hepatitis B-virus. Ook hepatitis C-virus- en JC-virusreactivatie zijn bij rituximab beschreven. Het risico op overige ernstige infecties lijkt bij alle biologicals ongeveer even hoog. Een bijzondere categorie zijn de Janus-kinase (JAK)-remmers, die zorgen voor een verminderde expressie van pro-inflammatoire genen. Van deze middelen is bekend dat ze waarschijnlijk een sterk verhoogd risico op herpes zoster geven. Onderzoek naar de invloed van deze middelen op het microbioom staat nog in de kinderschoenen: alleen van TNF-alfaremming is onderzocht wat dit doet op de darmkolonisatie

Infections in Biological and Targeted Synthetic Drug Use in Rheumatoid Arthritis:Where do We Stand? A Scoping Review and Meta-analysis

Introduction: The advent of biological and targeted synthetic therapies has revolutionized rheumatoid arthritis (RA) treatment. However, this has come at the price of an increased risk of infections. The aim of this study was to present an integrated overview of both serious and non-serious infections, and to identify potential predictors of infection risk in RA patients using biological or targeted synthetic drugs. Methods: We systematically reviewed available literature from PubMed and Cochrane and performed multivariate meta-analysis with meta-regression on the reported infections. Randomized controlled trials and prospective and retrospective observational studies including patient registry studies were analyzed, combined as well as separately. We excluded studies focusing on viral infections only. Results: Infections were not reported in a standardized manner. Meta-analysis showed significant heterogeneity that persisted after forming subgroups by study design and follow-up duration. Overall, the pooled proportions of patients experiencing an infection during a study were 0.30 (95% CI, 0.28–0.33) and 0.03 (95% CI, 0.028–0.035) for any kind of infections or serious infections only, respectively. We found no potential predictors that were consistent across all study subgroups. Conclusions: The high heterogeneity and the inconsistency of potential predictors between studies show that we do not yet have a complete picture of infection risk in RA patients using biological or targeted synthetic drugs. Besides, we found non-serious infections outnumbered serious infections by a factor 10:1, but only a few studies have focused on their occurrence. Future studies should apply a uniform method of infectious adverse event reporting and also focus on non-serious infections and their impact on treatment decisions and quality of life.</p

Test, trace, isolate:Evidence for declining SARS-CoV-2 PCR sensitivity in a clinical cohort

Real-time reverse transcription-polymerase chain reaction (RT-PCR) on upper respiratory tract (URT) samples is the primary method to diagnose SARS-CoV-2 infections and guide public health measures, with a supportive role for serology. We reinforce previous findings on limited sensitivity of PCR testing, and solidify this fact by statistically utilizing a firm basis of multiple tests per individual. We integrate stratifications with respect to several patient characteristics such as severity of disease and time since onset of symptoms. Bayesian statistical modelling was used to retrospectively determine the sensitivity of RT-PCR using SARS-CoV-2 serology in 644 COVID-19-suspected patients with varying degrees of disease severity and duration. The sensitivity of RT-PCR ranged between 80% − 95%; increasing with disease severity, it decreased rapidly over time in mild COVID-19 cases. Negative URT RT-PCR results should be interpreted in the context of clinical characteristics, especially with regard to containment of viral transmission based on ‘test, trace and isolate’

Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >= 2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.Peer reviewe

Re-emergence of enterovirus D68 in Europe after easing the COVID-19 lockdown, September 2021

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe

Burden of non-serious infections during biological use for rheumatoid arthritis

INTRODUCTION: Biologicals have become a cornerstone in rheumatoid arthritis (RA) treatment. The increased risk of serious infections associated with their use is well-established. Non-serious infections, however, occur more frequently and are associated with a high socioeconomic burden and impact on quality of life but have not received the same attention in the literature to date. The aim of this study was to gain insight into the various non-serious infections reported in RA patients using biologicals and their experienced burden.MATERIALS AND METHODS: The Dutch Biologic Monitor was a prospective observational study that included adults with rheumatoid arthritis and biological use who answered bimonthly questionnaires on the adverse drug reactions (ADRs) they experienced from their biological and reported the associated impact score (ranging from 1, no impact, to 5, very high impact). ADRs were assigned a MedDRA code by pharmacovigilance experts and labeled as definite, probable, possible or no infection by infectious disease professionals. Descriptive statistics were performed using medians and interquartile ranges.RESULTS: A total of 586 patients were included in the final analysis. Eighty-five patients (14.5%) reported a total of 421 ADRs labeled as probable or definite infections by the experts. Patient-assigned burden was ADR-specific. Upper respiratory tract infections were most frequently reported and had a high rate of recurrence or persistence, with a median impact score of 3.0 (IQR 2.0-3.0) which remained stable over time.DISCUSSION: Non-serious infections significantly outnumbered serious infections in this real-life cohort of RA patients using biologicals (77.1 non-serious infections and 1.3 serious infections per 100 patient years, respectively). Infections in the upper respiratory tract were rated as having an average burden, which remained constant over a long period of time. Awareness of the impact of recurrent and chronic non-serious infections may enable healthcare professionals to timely treat and maybe even prevent them, which would lessen the associated personal and socioeconomic burden.</p

The Impact of SARS-CoV-2 Immune Status and Societal Restrictions in Controlling COVID-19 across the World

To control the COVID-19 pandemic, many countries implemented vaccination and imposed societal restrictions both at the national level and for international travel. As a check of corona status, COVID passes have been issued. A COVID pass could be obtained when either fully vaccinated against COVID-19, or after recovering from a documented COVID-19 episode, or after a recent (24–48 h) negative SARS-CoV-2 antigen test. A global analysis of SARS-CoV-2 immune status determined by past infection and/or vaccination, vaccination rates, as well as societal restrictions in controlling the COVID-19 pandemic is presented. The data show that across the world, vaccination was more effective in reducing SARS-CoV-2 infections with the delta variant than the omicron variant. Strict societal restrictions could control spread of the virus, but relief of the restrictions was associated with an increase in omicron infections. No significant difference in SARS-CoV-2 infections were found when comparing countries or territories which did or did not implement a COVID pass

Infictieuze complicaties van biologicals bij de behandeling van reumatoïde artritis

De behandeling van reumatoïde artritis heeft een revolutie ondergaan sinds de introductie van biologicals. Een bekende complicatie van deze middelen is een verhoging van het risico op ernstige infecties, wat in verschillende mate bij de verschillende klassen voorkomt. Doordat TNF-alfaremmers onder andere granuloomvorming tegengaan, vormen ze een belangrijke risicofactor voor de reactivatie van latente tuberculose (tbc). Tocilizumab remt interleukine-6. Abatacept remt de T-celcostimulatie, waardoor een robuuste T-celrespons wordt tegengegaan. Rituximab, een monoclonaal dat CD20-positieve B-cellen depleteert, heeft als belangrijk risico reactivatie van hepatitis B-virus. Ook hepatitis C-virus- en JC-virusreactivatie zijn bij rituximab beschreven. Het risico op overige ernstige infecties lijkt bij alle biologicals ongeveer even hoog. Een bijzondere categorie zijn de Janus-kinase (JAK)-remmers, die zorgen voor een verminderde expressie van pro-inflammatoire genen. Van deze middelen is bekend dat ze waarschijnlijk een sterk verhoogd risico op herpes zoster geven. Onderzoek naar de invloed van deze middelen op het microbioom staat nog in de kinderschoenen: alleen van TNF-alfaremming is onderzocht wat dit doet op de darmkolonisatie