Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration.

BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

Rapid dereplication of microbial isolates using matrix-assisted laser desorption ionization time-of-flight mass spectrometry: A mini-review.

Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) has become one of the most popular methods for the rapid, cost-effective and accurate classification and characterization of cultivable microorganisms. Due to its simple sample preparation and short measurement time, MALDI-TOF MS is an excellent choice for the high-throughput study of microbial isolates from rhizospheres or plants grown under diverse environmental conditions. While clinical isolates have a higher identification rate than environmental isolates due to the focus of commercial mass spectral libraries on the former, no identification is necessary in the dereplication step of large environmental studies. The grouping of large sets of isolates according to their intact protein profiles can be performed without knowledge of their taxonomy. Thus, this method is easily applicable to environmental samples containing microorganisms from yet undescribed phylogenetic origins. The main strategies applied to achieve effective dereplication are, first, expanding existing mass spectral libraries and, second, using an additional statistical analysis step to group measured mass spectra and identify unique isolates. In this review, these aspects are addressed. It closes with a prospective view on how MALDI-TOF MS-based microbial characterisation can accelerate the exploitation of plant-associated microbiota.

Partner Choice Patterns Among the Descendants of Turkish Immigrants in Europe.

We examine the partner choice patterns of second-generation Turks in 13 European cities in seven countries. We not only compare intermarriage versus endogamous marriage, but also explicitly include the choice of a second-generation partner of the same origin and of a partner of other migrant origin as important alternatives. In Europe, populations are made up increasingly of migrants and their descendants resulting in new alternative partner options not open before. Findings suggest that second-generation Turks who choose a second-generation partner seem to be located between the partner choice of a first-generation and native partner in terms of family values and contact to non-coethnic peers. The choice of a partner of other migrant origin hardly differs in these characteristics from the choice of a native partner. Context variables such as group size and type of integration policies seem to play a role for the likelihood of having a first-generation versus a second-generation partner of Turkish origin but not for the likelihood of exogamous partner choice. A second-generation partner is the most popular choice in Germany but represents a minor option in the other countries. Furthermore, a partner of other migrant origin is more common among men but is in some countries more popular than a native partner among Turkish second-generation men and women.