Critical illness and intensive care unit admission are common occurrences in the immune-mediated inflammatory disease (IMID) patient cohort. This article specifically focuses on inflammatory rheumatic musculoskeletal disease within IMIDs. Understanding the aetiology, risk factors, co-morbidities, and management of these conditions in critical care are the key points discussed here. We have compiled the most common anti-rheumatic therapeutics in this article for management in these situations.

Background People with rheumatoid arthritis experience foot and lower limb pain due to active synovitis, resulting in impaired lower limb function. Earlier intervention may help with prevention of functional decline. The aims of this research were to develop and evaluate a new gait rehabilitation intervention for people with early rheumatoid arthritis, evaluate its feasibility, and to test whether or not gait rehabilitation plus usual care is more clinically and cost-effective than usual care alone. Design and methods We undertook a single-arm, repeated-measures, pre- and post-intervention, mixed-methods feasibility study with embedded qualitative components. We planned to undertake a pragmatic, two-arm, multicentre, superiority randomised controlled trial, with health economic evaluation, process evaluation and internal pilot. Setting and participants Participants with early rheumatoid arthritis (< 2 years post diagnosis) were identified from early arthritis and rheumatology outpatient clinics and referred for intervention in either podiatry or physiotherapy clinics. Intervention(s) Participants were randomised to a gait rehabilitation programme (Gait Rehabilitation Early Arthritis Trial Strides) involving a six-task gait circuit. Sessions were underpinned by motivational interviewing to facilitate behaviour change, supported by trained physiotherapists or podiatrists for a minimum of two sessions. Both groups received their normal usual care from the rheumatology multidisciplinary team. Main outcome measures Outcome measures for the feasibility study were intervention acceptability, adherence using the Exercise Adherence Rating Scale and fidelity using the Motivational Interviewing Treatment Integrity Scale. The main outcome measure for the internal pilot/randomised controlled trial was the Foot Function Index disability subscale. Outcomes were measured at baseline, 3 months, 6 months and 12 months. Other outcomes: intervention acceptability questionnaire, Exercise Adherence Rating Scale, exercise treatment beliefs via the Theory of Planned Behaviour Questionnaire, intervention fidelity (Motivational Interviewing Treatment Integrity Scale), health-related quality of life (EuroQol-5 Dimensions, five-level score). Results Thirty-five participants were recruited for feasibility and 23 (65.7%) completed 12-week follow-up. Intervention acceptability was excellent: 21/23 were confident that it could help and would recommend it and 22/23 indicated it made sense to them. Adherence was good, with a median (interquartile range) Exercise Adherence Rating Scale score of 17/24 (12.5–22.5). Twelve participants’ and nine therapists’ interviews confirmed intervention acceptability, identified perceptions of benefit, but highlighted some barriers to completion. Motivational Interviewing Treatment Integrity Scale scores demonstrated good fidelity. The trial did not progress from internal pilot to full main trial as a result of low recruitment and high attrition, after 53 participants were recruited from 9 sites over 12 months. Process evaluation confirmed good intervention acceptability and adherence, and fair fidelity. Evaluation of clinical and cost-effectiveness was not possible. Limitations Significant delays were experienced with the impact of coronavirus disease 2019, regulatory approvals, contracts and site readiness, resulting in few sites opening in time and low recruitment capacity. Foot and/or ankle pain prevalence was lower than anticipated, resulting in a low potential participant pool and a low conversion rate from screening to enrolment. Conclusions The Gait Rehabilitation Early Arthritis Trial Strides intervention was acceptable to people with early rheumatoid arthritis and intervention clinicians, safe, with good levels of adherence by participants, and fair intervention fidelity. The randomised controlled trial stopped early following failure to meet recruitment targets. Gait Rehabilitation Early Arthritis Trial Strides is a promising intervention that could be adapted for future evaluations. A definitive trial of the Gait Rehabilitation Early Arthritis Trial Strides gait rehabilitation intervention still needs to be done. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 15/165/04.

Background: Upadacitinib (UPA) is an oral, reversible, JAK inhibitor approved for treatment of moderate to severe rheumatoid arthritis (RA) and currently under evaluation for treatment of psoriatic arthritis (PsA). Objectives: To assess the efficacy and safety of UPA versus placebo (PBO) in patients (pts) with PsA and prior inadequate response or intolerance to ≥1 biologic disease-modifying anti-rheumatic drug (bDMARD). Methods: In SELECT-PsA-2, pts were randomized 1:1:1 to once daily UPA 15 mg (UPA15), UPA 30 mg (UPA30), or PBO. Pts were stratified by baseline DMARD use, number of prior failed bDMARDs, and extent of psoriasis. The primary endpoint was the proportion of pts achieving ACR20 response at Wk 12. Multiplicity controlled secondary endpoints included change in HAQ-DI, FACIT-Fatigue (FACIT-F), and SF-36 Physical Component Summary (PCS) at Wk 12; static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline, PASI75, and change in Self-Assessment of Psoriasis Symptoms (SAPS) at Wk 16; and proportion of pts achieving MDA at Wk 24. Additional key secondary endpoints were ACR50 and ACR70 at Wk 12, and ACR20 at Wk 2. Treatment-emergent adverse events (TEAEs) are reported for pts who received ≥1 dose of study drug. Results: 641 pts were randomized and received study drug; 54.3% were female with mean age of 53.4 years, and mean duration since PsA diagnosis of 10.1 years. 61% of pts failed 1 bDMARD, 18% failed 2 bDMARDs, and 13% failed ≥3 bDMARDs. 543 (84.6%) pts completed Wk 24 study drug. At Wk 12, a significantly greater proportion of pts receiving UPA15 and UPA30 vs PBO achieved ACR20 (56.9% and 63.8% vs 24.1%; p < .0001 for both comparisons). Statistically significant improvements were observed in the UPA15 and UPA30 arms vs PBO in all multiplicity controlled secondary endpoints, including ΔHAQ-DI (PBO, -0.10; UPA15, -0.30; UPA30, -0.41), ΔSF-36 PCS (PBO, 1.6; UPA15, 5.2; UPA30, 7.1), ΔFACIT-F (PBO, 1.3; UPA15, 5.0; UPA30, 6.1), and ΔSAPS (PBO, -1.5; UPA15, -24.4; UPA30, -29.7; p < .0001 for all endpoints; Figure 1 ). In addition, a greater proportion of pts achieved ACR50 and ACR70 at Wk 12 with UPA vs PBO. Generally, TEAEs were reported at similar frequencies in the PBO and UPA15 arms and at a higher frequency in the UPA30 arm ( Figure 2 ). Numerically higher rates of serious AEs were reported in the UPA arms. Herpes zoster was more frequent with UPA30. Three malignancies occurred in each of the UPA arms. One adjudicated non-fatal myocardial infarction and one adjudicated pulmonary embolism were reported with UPA15. Conclusion: In this bDMARD-IR PsA population, UPA15 and UPA30 demonstrated significant improvements across PsA domains including improvements in joint and skin signs and symptoms vs PBO through Wk 24 with improvement observed by Wk 2. A greater percentage of pts treated with UPA achieved MDA and ACR50/70, stringent composite measures of disease control. No new safety signals were identified compared to what has been observed with UPA in RA. Disclosure of Interests: Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Apinya Lertratanakul Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jaclyn Anderson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kim Papp Grant/research support from: AbbVie, Amgen, Astellas, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Takeda, UCB, and Valeant., Consultant of: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, Speakers bureau: AbbVie, Amgen, Astellas, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa-Hakko Kirin, Leo Pharma, MedImmune, Merck-Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Stiefel, Sun Pharma, Takeda, UCB, and Valeant, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Filip van den Bosch Consultant of: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Speakers bureau: AbbVie, Celgene Corporation, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer, and UCB, Shigeyoshi Tsuji Grant/research support from: Eli Lilly, Speakers bureau: AbbVie, Asahi Kasei, Chugai, Daiichi Sankyo, Eli Lilly, Eisai, Mitsubishi Tanabe, Celgene, and Novartis Pharma K.K., Eva Dokoupilova Grant/research support from: Eli Lilly, AbbVie, Novartis, MAURO KEISERMAN Speakers bureau: Pfizer, Abbott, Actelion, AstraZeneca, Amgen, Roche, Bristol Myers Squibb, and Janssen and has received clinical trial honoraria from Pfizer, Amgen, AstraZeneca, Anthera Pharmaceuticals, Bristol-Myers Squibb, Biogen Idec Inc, Celltrion Inc., Eli Lilly, Human Genome Sciences, Novartis, Roche, Sanofi, UCB Inc., xin wang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Sheng Zhong Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Patrick Zueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Compounds that target interleukin (IL)−6 pathways include antibodies against the IL-6 receptor or ligand, and inhibitors of IL-6 signal transduction. The anti-IL-6 receptor (IL-6R) monoclonal antibody tocilizumab has been licensed for several years; data from multiple studies demonstrate its efficacy and tolerability in rheumatoid arthritis as monotherapy or in combination with methotrexate. In addition, another anti-IL-6R monoclonal antibody, sarilumab, has recently been approved in both the US and EU. Anti-IL-6 monoclonal antibodies include olokizumab and clazakizumab, which both have data from phase II studies, as well as sirukumab which has completed phase III trials but may not be brought to the market. Comparative data for olokizumab versus tocilizumab intervention in rheumatoid arthritis suggest no difference in efficacy between blocking the receptor or the ligand. Head-to-head studies are needed to determine whether inhibition of the Janus kinase pathway is similar in its overall efficacy to direct inhibition of IL-6 or its receptor. The IL-6 inhibitors appear to be more effective when combined with methotrexate. However, they have shown superiority to tumour necrosis factor inhibitors when used as monotherapy, and may have an advantage in patients who cannot use methotrexate or any other conventional synthetic disease modifying anti-rheumatic drug. Regarding disease activity assessment, CDAI is a more appropriate measure than DAS28 when looking at the effect of IL-6 inhibition, as these agents interfere with the acute phase response, which is heavily weighted in the formula of DAS28.

The cytokine interleukin (IL)−6 performs a diverse portfolio of functions in normal physiology and disease. These functions extend beyond the typical role for an inflammatory cytokine, and IL-6 often displays hormone-like properties that affect metabolic processes associated with lipid metabolism, insulin resistance, and the neuroendocrine system. Consequently, the biology of IL-6 is complex. Recent advances in the field have led to novel interpretations of how IL-6 delivers immune homeostasis in health and yet drives disease pathology during infection, autoimmunity, and cancer. Various biological drugs that target IL-6 are in clinical practice or emerging in clinical trials and pre-clinical development programmes. The challenge is knowing how and when to apply these therapies. In this review, we will explore the biology behind IL-6 directed therapies and identify some key hurdles for future investigation.