ObjectivesTo assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early rheumatoid arthritis (RA) inception cohorts with a focus on methotrexate (MTX) exposure.DesignMulticentre prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN).SettingSecondary care, ERAS nine centres, ERAN 23 centres in England, Wales and Ireland.ParticipantsPatients with new diagnosis of RA, n=2701. Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3–6 months, at 12 months and annually thereafter.Primary and secondary outcome measuresPrimary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA-specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis.ResultsOf 92 eligible ILD cases, 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases. The primary analysis of RA-ILD cases only developing after any conventional synthetic disease-modifying antirheumatic drug treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and a non-significant trend for delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004) and longer time to ILD diagnosis (OR 0.41, 95% CI 0.23 to 0.75, p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.ConclusionsMTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary, evidence suggested that MTX may delay the onset of ILD.
Current literature addressing the pharmacological principles guiding glucocorticoid (GC) administration in ARDS is scant. This paucity of information may have led to the heterogeneity of treatment protocols and misinterpretation of available findings. GCs are agonist compounds that bind to the GC receptor (GR) producing a pharmacological response. Clinical efficacy depends on the magnitude and duration of exposure to GR. We updated the meta-analysis of randomized trials investigating GC treatment in ARDS, focusing on treatment protocols and response. We synthesized the current literature on the role of the GR in GC therapy including genomic and non-genomic effects, and integrated current clinical pharmacology knowledge of various GCs, including hydrocortisone, methylprednisolone and dexamethasone. This review addresses the role dosage, timing of initiation, mode of administration, duration, and tapering play in achieving optimal response to GC therapy in ARDS. Based on RCTs’ findings, GC plasma concentration–time profiles, and pharmacodynamic studies, optimal results are most likely achievable with early intervention, an initial bolus dose to achieve close to maximal GRα saturation, followed by a continuous infusion to maintain high levels of response throughout the treatment period. In addition, patients receiving similar GC doses may experience substantial between-patient variability in plasma concentrations affecting clinical response. GC should be dose-adjusted and administered for a duration targeting clinical and laboratory improvement, followed by dose-tapering to achieve gradual recovery of the suppressed hypothalamic–pituitary–adrenal (HPA) axis. These findings have practical clinical relevance. Future RCTs should consider these pharmacological principles in the study design and interpretation of findings. Electronic supplementary material The online version of this article (10.1007/s00134-020-06289-8) contains supplementary material, which is available to authorized users.
Physical and mental illnesses are driven by ethnicity, social, environmental and economic determinants. Novel theoretical frameworks in rheumatoid arthritis (RA) focus on links and adverse interactions between and within biological and social factors. This review aimed to summarise associations between socioeconomic status (SES) and RA disease activity, and implications for future research. Articles studying the association between SES and RA disease activity were identified, from 1946 until March 2021. The research question was: Is there an association between social deprivation and disease activity in people with RA? Articles meeting inclusion criteria were examined by one author, with 10% screened at abstract and full paper stage by a second author. Disagreements were resolved with input from a third reviewer. Information was extracted on definition/measure of SES, ethnicity, education, employment, comorbidities, disease activity and presence/absence of association between SES and disease activity. Initially, 1750 articles were identified, with 30 articles ultimately included. SES definition varied markedly—10 articles used a formal scale and most used educational attainment as a proxy. Most studies controlled for lifestyle factors including smoking and body mass index, and comorbidities. Twenty-five articles concluded an association between SES and RA disease activity; two were unclear; three found no association. We have demonstrated the association between low SES and worse RA outcomes. There is a need for further research into the mechanisms underpinning this, including application of mixed-methods methodology and consideration of syndemic frameworks to understand bio–bio and bio–social interactions, to examine disease drivers and outcomes holistically.
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