Janus kinase (JAK) Inhibitors are the latest drug class of disease-modifying medication to emerge for the treatment of rheumatoid arthritis (RA). They are a small molecule-targeted treatment and are the first oral option to compare favourably to existing biologic disease-modifying anti-rheumatic drugs (DMARDs). Tofacitinib, baricitinib and upadacitinib are the first 3 JAK inhibitors to become commercially available in the field and are the core focus of this review. To date, they have demonstrated comparable efficacy to tumour necrosis factor (TNF) inhibitors in terms of American College of Rheumatology (ACR) response rates and disease activity (DAS28) scores with similar cost to the benchmark adalimumab. This narrative review article aims to synthesise and distil the key available trial data on JAK inhibitor efficacy and safety, along with their place in the ACR and European League Against Rheumatism (EULAR) guidelines for RA. The novel mechanism of action of the JAK/STAT pathway is highlighted along with the potential effects of modulating each pathway. The rapid onset of action, role in attenuation of central pain processing and effect on structural damage and radiographic progression are also all examined in detail. We also explore the latest meta-analyses and comparative performance of each of the 3 available JAKs in an effort to determine which is most efficacious and which has the most favourable safety profile. Post marketing concerns regarding thromboembolism risk and herpes zoster infection are also discussed. Additionally, we review the cost-benefit analyses of the available JAK inhibitors and address some of the pharmacoeconomic considerations for real-world practice in the UK and US by detailing the raw acquisition cost and the value they provide in comparison to the benchmark biologic adalimumab and the anchor DMARD methotrexate.

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Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) are a feature of the idiopathic inflammatory myopathies (IIM), but are also seen in other rheumatic diseases, and in individuals with no clinical symptoms. The aim of this study was to assess the clinical utility of MSA and MAA and in particular the clinical relevance of weakly positive results. We included all patients at our institution who had at least one positive result on the Immunoblot EUROLINE myositis panel over a 6-year period (2015–2020). Associations with clinical features and final diagnosis were evaluated. Eighty-seven of 225 (39%) myositis panel tests met the inclusion criteria. There were 52 strong positives and 35 weak positives for one or more MSA/MAAs. Among the strong positive group, 15% (8/52) were diagnosed with IIM, 34.6% (18/52) with interstitial lung disease, 7.7% (4/52) with anti-synthetase syndrome, 25% (13/52) with connective tissue disease, and others accounted for 25% (13/52). In weak-positive cases, only 14% (5/35) had connective tissue disease and none had IIM. 60% (21/35) of weak-positive cases were not associated with a specific rheumatic disease. A significant number of positive myositis panel results, particularly weak positives, are not associated with IIM or CTD.

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Rheumatoid arthritis (RA) is a common systemic rheumatic disease. While the most visible manifestation of RA is articular involvement, it is a true systemic disease with the potential to affect multiple organs. Methotrexate (MTX) is the most commonly used medication to treat RA. MTX pneumonitis (MTX-pneu) is a rare disease entity reported in MTX users. It usually develops acutely or subacutely in the first year of treatment. MTX-pneu presents with cough, dyspnoea, and often fever. Pre-existing lung disease is a major risk factor and the clinical diagnosis is based on MTX exposure, symptoms, and laboratory and imaging findings. Treatment involves MTX cessation and high-dose glucocorticoids. Interstitial lung disease (ILD) is a common manifestation of RA with clinical RA-ILD affecting up to 10% of patients. RA-ILD tends to be a more indolent process than MTX-pneu and frequently develops over years but can also be acute. Similar to MTX-pneu, RA-ILD presents with cough, dyspnoea, and often fever. Risk factors include age, male sex, disease activity, seropositivity, and smoking. Treatment is aimed at optimal control of RA disease and within this strategy there may be particular roles for rituximab, tocilizumab, and abatacept. Antifibrotics may also have a role. Given the distinct pathologies, the differentiation of these two entities is crucial. The treatment approach differs significantly and what is beneficial for one may be harmful for the other. In this paper, the authors discuss and contrast contemporary knowledge of MTX-pneu and RA-ILD.