EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update.

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Differences in phenology, daily timing of activity, and associations of temperature utilization with survival in three threatened butterflies.

We used observational data collected during a mark-recapture study that generated a total of 7503 captures of 6108 unique individuals representing three endangered butterfly species to quantify inter-and intraindividual variation in temperature utilization and examine how activity patterns vary according to season, time of day, and ambient temperature. The Marsh Fritillary, the Apollo, and the Large Blue differed in utilized temperatures and phenology. Their daily activity patterns responded differently to temperature, in part depending on whether they were active in the beginning, middle or end of the season, in part reflecting interindividual variation and intraindividual flexibility, and in part owing to differences in ecology, morphology, and colouration. Activity temperatures varied over the season, and the Apollo and the Large Blue were primarily active at the highest available ambient temperatures (on the warmest days and during the warmest part of the day). The Marsh Fritillary was active early in the season and decreased activity during the highest temperatures. The relationship between individual lifespan and the average temperature was qualitatively different in the three species pointing to species-specific selection. Lifespan increased with an increasing range of utilized temperatures in all species, possibly reflecting that intra-individual flexibility comes with a general survival benefit.