Early differentiation between infection and aseptic inflammation is difficult and is a challenge often faced in the rheumatology practice. Procalcitonin (PCT) is a biomarker that is preferentially induced in patients with bacterial infections, and a growing body of evidence supports its use for improving diagnosis of bacterial infections and guiding antibiotic therapy. In this article, we review the evidence for the use of PCT measurement in rheumatology practice. Several studies have examined the use of PCT to assist in the differentiation between septic and non-septic arthritis in patients with an inflamed joint and found it to be a sensitive and specific marker of infection. A number of studies in patients with diverse inflammatory rheumatic diseases have provided useful information regarding the usefulness of PCT in these patients. In summary, PCT when used in the appropriate clinical setting can be a useful adjunct to currently available laboratory infection markers, though further studies are warranted. Furthermore, PCT results should be interpreted in parallel with the clinical assessment.
Rheumatology teams care for patients with diverse, systemic autoimmune diseases who are often immunosuppressed and at high risk of infections. The current COVID-19 pandemic has presented particular challenges in caring for and managing this patient group. The office of the chief medical officer (CMO) for England contacted the rheumatology community to provide expert advice on the identification of extremely vulnerable patients at very high risk during the COVID-19 pandemic who should be 'shielded'. This involves the patients being asked to strictly self-isolate for at least 12 weeks with additional funded support provided for them to remain at home. A group of rheumatologists (the authors) have devised a pragmatic guide to identifying the very highest risk group using a rapidly developed scoring system which went live simultaneous with the Government announcement on shielding and was cascaded to all rheumatologists working in England.
Background Current rheumatoid arthritis therapies target immune inflammation and are subject to ceiling effects. Seliciclib is an orally available cyclin-dependent kinase inhibitor that suppresses proliferation of synovial fibroblastscells not yet targeted in rheumatoid arthritis. Part 1 of this phase 1b/2a trial aimed to establish the maximum tolerated dose of seliciclib in patients with active rheumatoid arthritis despite ongoing treatment with TNF inhibitors, and to evaluate safety and pharmacokinetics. Methods Phase 1b of the TRAFIC study was a non-randomised, open-label, dose-finding trial done in rheumatology departments in five UK National Health Service hospitals. Eligible patients (aged ≥18 years) fulfilled the 1987 American College of Rheumatology (ACR) or the 2010 ACR-European League Against Rheumatism classification criteria for rheumatoid arthritis and had moderate to severe disease activity (a Disease Activity Score for 28 joints [DAS28] of ≥3•2) despite stable treatment with anti-TNF therapy for at least 3 months before enrolment. Participants were recruited sequentially to a maximum of seven cohorts of three participants each, designated to receive seliciclib 200 mg, 400 mg, 600 mg, 800 mg, or 1000 mg administered in 200 mg oral capsules. Sequential cohorts received doses determined by a restricted, one-stage Bayesian continual reassessment model, which determined the maximum tolerated dose (the primary outcome) based on a target dose-limiting toxicity rate of 35%. Seliciclib maximum concentration (C max) and area under the plasma concentration time curve 0-6 h (AUC 0-6) were measured. This study is registered with ISRCTN, ISRCTN36667085.
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