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Objective To perform a systematic literature review on definitions and instruments used to measure remission, relapse and disease activity in polymyalgia rheumatica (PMR), to inform an OMERACT project to endorse instruments for these outcomes. Methods A search of Pubmed/MEDLINE, EMBASE, CINAHL, Cochrane and Epistemonikos was performed May 2021 and updated August 2023. Qualitative and quantitative studies published in English were included if they recruited people with isolated PMR regardless of treatment. Study selection and data extraction was performed independently by two investigators and disagreement was resolved through discussion. Data extracted encompassed definitions of disease activity, remission and relapse, and details regarding the instruments used to measure these outcomes. Results From the 5718 records, we included 26 articles on disease activity, 36 on remission and 53 on relapse; 64 studies were observational and 15 interventional, and none used qualitative methods. Some heterogeneity was found regarding definitions and instruments encompassing the domains pain, stiffness, fatigue, laboratory markers (mainly acute phase reactants), and patient and physician global assessment of disease activity. However, instruments for clinical signs were often poorly described. Whilst measurement properties of the polymyalgia rheumatica activity score (PMR-AS) have been assessed, data to support its use for measurement of remission and relapse are limited. Conclusion Remission, relapse and disease activity have been defined heterogeneously in clinical studies. Instruments to measure these disease states still need to be validated. Qualitative research is needed to better understand the concepts of remission and relapse in PMR. Review registration PROSPERO identification: CRD42021255925. [ABSTRACT FROM AUTHOR]

The authors discuss the article "Prevalence, characteristics, and outcome of subclinical vasculitis in polymyalgia rheumatica: a retrospective cohort study" by L. Moreel and colleagues, published in the issue. Topics include the idea of an overlap between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), scan findings of patients with isolated PMR symptoms, and comparison of the key study characteristics for Morreel and colleagues and E. De Miguel and colleagues.

The article focuses on the evolving understanding and management of polymyalgia rheumatica (PMR), highlighting advancements in diagnosis, including the use of imaging techniques, and the shift towards incorporating steroid-sparing agents and disease-modifying antirheumatic drugs (DMARDs) in treatment. Topics include the diagnostic work-up for PMR, management approaches for newly diagnosed and relapsing disease, and the potential role of biologic agents in transforming PMR management.

The impact of modern imaging in uncovering the underlying pathology of PMR cannot be understated. Long dismissed as an inflammatory syndrome with links to the large vessel vasculitis giant cell arteritis (GCA), a pathognomonic pattern of musculotendinous inflammation is now attributed to PMR and may be used to confirm its diagnosis. Among the available modalities, 18F-fluorodeoxyglucose (18F-FDG) PET/CT is increasingly recognized for its high sensitivity and specificity, as well as added ability to detect concomitant large vessel GCA and exclude other relevant differentials like infection and malignancy. This atlas provides a contemporary depiction of PMR's pathology and outlines how this knowledge translates into a pattern of findings on whole body 18F-FDG PET/CT that can reliably confirm its diagnosis. [ABSTRACT FROM AUTHOR]

Aim: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) correlate with disease activity in several rheumatic diseases; however, their utility in polymyalgia rheumatica (PMR) remains unclear. This study evaluated their relationship with disease activity and glucocorticoid resistance in PMR. Method: Data for disease activity (PMR‐AS) and full blood examination was obtained from a prospective observational cohort comprising newly diagnosed, steroid‐naïve PMR patients treated with low‐dose glucocorticoid therapy. Glucocorticoid resistance was defined as non‐response to prednisolone 15 mg/d or initial response followed by flare (PMR‐AS ≥ 9.35 or ∆ ≥6.6) upon weaning to 5 mg/d. Univariable Bayesian linear regression analysis of the relationship between PMR‐AS (baseline and mean) and NLR and PLR was performed. Predictors of glucocorticoid resistance were identified using a multivariable outcome model, with variables derived from Bayesian model selection. Results: Of the 32 included patients, 16 (50%) fulfilled the primary outcome measure of glucocorticoid resistance. These participants were older, typically female, and had higher baseline C‐reactive protein than their glucocorticoid‐responsive counterparts. A statistically significant relationship was identified between PMR‐AS and both NLR (odds ratio [OR] 28.1; 95% CI 1.6‐54.7) and PLR (OR 40.6; 95% CI 10.1‐71.4) at baseline, with PLR also found to correlate with disease activity during follow‐up (OR 15.6; 95% CI 2.7‐28.2). Baseline NLR proved a statistically significant predictor of glucocorticoid‐resistant PMR (OR 14.01; 95% CI 1.49‐278.06). Conclusion: Baseline NLR can predict glucocorticoid resistance in newly diagnosed PMR patients. Both NLR and PLR may be reliable biomarkers of disease activity in PMR. [ABSTRACT FROM AUTHOR]

Objectives: To characterize 18F-fluorodeoxyglucose (18F-FDG) uptake on whole-body PET/CT in PMR, and identify its precise anatomic correlate using MRI. Methods: Patients with newly diagnosed PMR according to the 2012 EULAR/ACR classification criteria were prospectively recruited. Participants with GCA were excluded. A whole-body 18F-FDG PET/CT scan was performed in all untreated patients. Qualitative and semiquantitative [standardized uptake value maximum (SUVmax)] scoring of abnormal 18F-FDG uptake was undertaken. MRI of the pelvis, knee and wrist and hand was performed in three representative patients with anatomical correlation of FDG-avid sites carried out using Medview fusion software. Results: Twenty-two patients with PMR were recruited. Their mean age was 68.3 years (s.d. 6.3) and 13/22 were male. On whole-body PET/CT, 18F-FDG uptake adjacent to the ischial tuberosities was observed in 21 participants (95.4%) and recorded the highest mean SUVmax value [3.6 (s.d. 1.7)]. A high frequency of posteromedial knee (61.9%) and wrist and/or hand involvement (66.7%) was also appreciated. MRI of the pelvis revealed high T2 signal surrounding the proximal hamstring tendon origins of both semimembranosus and the conjoint tendon of the semitendinosus and biceps femoris. At the knee, peritendonitis at the distal insertion of the semimembranosus was observed. PET/MRI fusion at the pelvis and knee confirmed semimembranosus peritendonitis as the anatomical correlate of 18F-FDG uptake adjacent to the ischial tuberosities and of posteromedial knee structures. Conclusion: Hamstring peritendonitis is a common and distinctive manifestation of PMR on whole-body PET/CT. Trial registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au, ACTRN1261400696695. [ABSTRACT FROM AUTHOR]

Polymyalgia rheumatica is a common inflammatory condition but can be difficult to diagnose. Treatment is warranted in all cases to manage disabling symptoms. Low-moderate doses of oral corticosteroids are highly effective. Once symptoms improve they can often be gradually reduced over months, but most patients require either prolonged or continuous treatment. Despite their effectiveness, corticosteroids cause disproportionate damage in polymyalgia rheumatica compared to other rheumatic diseases. The therapeutic aim is to prescribe the minimum possible dose required for symptom control. There is a lack of definitive evidence for steroid-sparing drugs in polymyalgia rheumatica. Methotrexate is typically used for relapsing disease. Leflunomide and tocilizumab are being investigated, but further research is needed. [ABSTRACT FROM AUTHOR]

Objective: An unmet need exists for glucocorticoid-sparing treatments for patients with polymyalgia rheumatica (PMR). The antibody-drug conjugate ABBV-154 comprises adalimumab conjugated to a glucocorticoid receptor modulator. We evaluated ABBV-154 versus placebo in patients with glucocorticoid-dependent PMR., Methods: In this phase 2, randomized, double-blind, placebo-controlled, dose-ranging study, eligible patients had confirmed PMR, glucocorticoid response and ≥2 unequivocal PMR flares while tapering glucocorticoids and still on ≥ 5 mg daily prednisone equivalent. Randomized patients received subcutaneous placebo or ABBV-154 40, 150, or 340 mg once every other week. The primary efficacy endpoint was time to flare. The sponsor voluntarily terminated the study early., Results: Overall, 181 patients were randomized (placebo, n = 50; ABBV-154: 40 mg, n = 42; 150 mg, n = 45; 340 mg, n = 44) and 67.4% completed study drug at week 24 Time to flare was longer for patients receiving ABBV-154 than those receiving placebo, with Kaplan-Meier estimate of 24-week flare-free rate being lower for placebo. The hazard ratios of ABBV-154 vs placebo (95% confidence interval) were 0.49 (0.27, 0.88), P = 0.017 for 40 mg; 0.44 [0.25, 0.79], P = 0.006 for 150 mg; 0.20 [0.09, 0.42], P < 0.001 for 340 mg. Incidences of treatment-emergent adverse events were similar between groups, and the most common across ABBV-154 cohorts was COVID-19 (16.0%)., Conclusion: Treatment effects were observed for ABBV-154 cohorts compared with placebo for time to flare. ABBV-154 was generally well tolerated. Due to early study termination, results should be interpreted with caution., Clinicaltrials: gov identifier: NCT04972968., (This article is protected by copyright. All rights reserved.)

Polymyalgia rheumatica (PMR) immune-related adverse events (ICI-PMRs) represent a novel, distinct entity, despite many clinical, laboratory, and imaging similarities to classical PMR. Important questions remain in differentiating ICI-PMR from classical PMR, as well as other immune-related adverse events and PMR mimics. Despite this, ICI-PMR currently takes treatment cues from classical PMR, albeit with considerations relevant to cancer immunotherapy. Comparisons between ICI-PMR and classical PMR may provide further bidirectional insights, especially given that important questions remain unanswered about both diseases. The cause of classical PMR remains poorly understood, and ICI-PMR may represent a model of induced PMR, with important therapeutic implications., Competing Interests: Disclosure No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the study described in this article. D.F.L. Liew and R.R.C. Buchanan declare no relevant interests. C.E. Owen declares: consultancy and advisory board participation for Abbvie; speaking honoraria from Abbvie, Janssen, Novartis, and Roche. A. Tison declares consulting fees from Galapagos, speakers bureaus from Bristol-Myers Squibb, congress fees: Sanofi and Abbvie. S.L. Mackie reports: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, and Pfizer; Investigator on clinical trials for Sanofi, GSK, and Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis, and AbbVie; chief investigator on STERLING-PMR trial, funded by the National Institute for Health and Care Research (NIHR); patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. S.L. Mackie is supported in part by the NIHR Leeds Biomedical Research Center. The views expressed in this article are those of the authors and not necessarily those of the NIHR, the NIHR Leeds Biomedical Research Center, the National Health Service or the UK Department of Health and Social Care. M. Yates reports advisory board fees for BioGen. S.E. Sattui is by the Bristol Myers Squibb Foundation Robert A. Winn Diversity in Clinical Trials Career Development Award. S.E. Sattui has received research funding from AstraZeneca and GlaxoSmithKline (clinical trials) and participated in consulting and advisory boards for Sanofi and Amgen (funds toward research support). S.E. Sattui has received speaker fees from Fresenius Kabi (funds toward research support). D.F.L. Liew conceptualized the article, and wrote the original draft. All authors were responsible for drafting, reviewing, and editing the final article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The impact of modern imaging in uncovering the underlying pathology of PMR cannot be understated. Long dismissed as an inflammatory syndrome with links to the large vessel vasculitis giant cell arteritis (GCA), a pathognomonic pattern of musculotendinous inflammation is now attributed to PMR and may be used to confirm its diagnosis. Among the available modalities, 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/CT is increasingly recognized for its high sensitivity and specificity, as well as added ability to detect concomitant large vessel GCA and exclude other relevant differentials like infection and malignancy. This atlas provides a contemporary depiction of PMR's pathology and outlines how this knowledge translates into a pattern of findings on whole body 18 F-FDG PET/CT that can reliably confirm its diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)