ANCA-associated vasculitis with muscle involvement mimicking polymyalgia rheumatica.

We report a case of a woman in her early 80s with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented as myalgia mimicking polymyalgia rheumatica (PMR). She had positive results for the Neer and Hawkins-Kennedy impingement tests, and a normal serum creatine kinase (CK) concentration. At first, we suspected PMR; however, the patient did not strictly meet the classification criteria. Electromyography revealed an abnormal myogenic pattern, and muscle MRI revealed intramuscular and fascial hyperintensity. Moreover, chest CT revealed interstitial lung disease, and test results for ANCAs were positive. We diagnosed the patient with ANCA-associated vasculitis based on the criteria and treated her with corticosteroids and rituximab. Thus, ANCA-associated vasculitis can cause muscle involvement without elevation of the CK concentration and mimic PMR.

Investigational agents for polymyalgia rheumatica treatment: assessing the critical needs for future development.

INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disorder characterized by pain and stiffness in the shoulder and pelvic girdles, constitutional symptoms, and elevated acute-phase reactants. Glucocorticoids (GCs) remain the first-choice treatment for PMR, but relapses are common. Identification of steroid-sparing agents is therefore of utmost importance. AREAS COVERED: The efficacy of conventional immunosuppressive drugs is controversial. The use of interleukin (IL)-6 receptor inhibitors proved to be effective and safe in treating PMR patients. Currently, there are 12 ongoing clinical trials exploring potential treatments such as leflunomide, low-dose IL-2, rituximab, abatacept, secukinumab, Janus kinase inhibitors, and selective inhibitors like SPI-62 and ABBV 154. EXPERT OPINION: The high efficacy of IL-6 R receptor inhibitors as well as the numerous drug trials currently recruiting suggest that several therapeutic options will be available in the near future. Accurate diagnosis and early stratification of PMR patients according to the giant cell arteritis-PMR Spectrum Disease 'GPSD' and potential risk factors for relapsing disease or GC-related adverse events are crucial to identify patients who would benefit most from GC-sparing agents. The development of internationally accepted definitions for remission and relapse is urgently needed. Early referral strategies to specialist settings would improve disease stratification and personalized treatment.

Polymyalgia rheumatica shows metabolomic alterations that are further altered by glucocorticoid treatment: Identification of metabolic correlates of fatigue.

OBJECTIVE: In polymyalgia rheumatica (PMR), glucocorticoids (GCs) relieve pain and stiffness, but fatigue may persist. We aimed to explore the effect of disease, GCs and PMR symptoms in the metabolite signatures of peripheral blood from patients with PMR or the related disease, giant cell arteritis (GCA). METHODS: Nuclear magnetic resonance spectroscopy was performed on serum from 40 patients with untreated PMR, 84 with new-onset confirmed GCA, and 53 with suspected GCA who later were clinically confirmed non-GCA, and 39 age-matched controls. Further samples from PMR patients were taken one and six months into glucocorticoid therapy to explore relationship of metabolites to persistent fatigue. 100 metabolites were identified using Chenomx and statistical analysis performed in SIMCA-P to examine the relationship between metabolic profiles and, disease, GC treatment or symptoms. RESULTS: The metabolite signature of patients with PMR and GCA differed from that of age-matched non-inflammatory controls (R2 > 0.7). There was a smaller separation between patients with clinically confirmed GCA and those with suspected GCA who later were clinically confirmed non-GCA (R2 = 0.135). In PMR, metabolite signatures were further altered with glucocorticoid treatment (R2 = 0.42) but did not return to that seen in controls. Metabolites correlated with CRP, pain, stiffness, and fatigue (R2 ≥ 0.39). CRP, pain, and stiffness declined with treatment and were associated with 3-hydroxybutyrate and acetoacetate, but fatigue did not. Metabolites differentiated patients with high and low fatigue both before and after treatment (R2 > 0.9). Low serum glutamine was predictive of high fatigue at both time points (0.79-fold change). CONCLUSION: PMR and GCA alter the metabolite signature. In PMR, this is further altered by glucocorticoid therapy. Treatment-induced metabolite changes were linked to measures of inflammation (CRP, pain and stiffness), but not to fatigue. Furthermore, metabolite signatures distinguished patients with high or low fatigue.

Rheumatology: What You May Have Missed in 2023.

Many patients with rheumatologic conditions receive care from physicians other than rheumatologists. Here we note key findings from 6 studies in rheumatology published in 2023 that offer valuable insights for internal medicine specialists and subspecialists outside of rheumatology. The first study investigated the effect of low-dose glucocorticoids on patients with rheumatoid arthritis (RA) over 2 years and challenged existing perceptions about the risks of glucocorticoids in this setting. The second study focused on the updated guideline for preventing and treating glucocorticoid-induced osteoporosis. With the chronic and widespread use of glucocorticoids, the American College of Rheumatology emphasized the importance of assessing fracture risk and initiating pharmacologic therapy when appropriate. The third study explored the potential use of methotrexate in treating inflammatory hand osteoarthritis, suggesting a novel approach to managing this challenging and common condition. The results of the fourth article we highlight suggest that sarilumab has promise as an adjunct treatment of polymyalgia rheumatica relapse during glucocorticoid dosage tapering. The fifth study evaluated sublingual cyclobenzaprine for fibromyalgia treatment, noting both potential benefits and risks. Finally, the sixth article is a systematic review and meta-analysis that assessed the therapeutic equivalence of biosimilars and reference biologics in the treatment of patients with RA. Knowledge of this recent literature will be useful to clinicians regardless of specialty who care for patients with these commonly encountered conditions.

Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.

OBJECTIVE: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR). METHODS: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts. RESULTS: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6). CONCLUSION: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Immune Checkpoint Inhibitor-induced Polymyalgia Rheumatica.

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.

Concordance and agreement between different activity scores in polymyalgia rheumatica.

OBJECTIVE: The C reactive protein polymyalgia rheumatica activity score (CRP-PMR-AS) is a composite index that includes CRP levels and was developed specifically for PMR. As treatments such as interleukin-6 antagonists can normalise CRP levels, the erythrocyte sedimentation rate (ESR) of PMR-AS, the clinical (clin)-PMR-AS and the imputed-CRP (imp-CRP)-PMR-AS have been developed to avoid such bias. Our primary objective was to measure the correlation of these activity scores. Our secondary objective was to evaluate the concordance between different cutoffs of the PMR-ASs. METHOD: Data from the Safety and Efficacy of tocilizumab versus Placebo in Polymyalgia rHeumatica With glucocORticoid dEpendence (SEMAPHORE) trial, a superiority randomised double-blind placebo-controlled trial, were subjected to post hoc analysis to compare the efficacy of tocilizumab versus placebo in patients with active PMR. The CRP-PMR-AS, ESR-PMR-AS, clin-PMR-AS and imp-CRP-PMR-AS were measured at every visit. The concordance and correlation between these scores were evaluated using kappa correlation coefficients, Bland-Altman correlations, intraclass correlation coefficients (ICCs) and scatter plots. RESULTS: A total of 101 patients were included in the SEMAPHORE trial, and 100 were analysed in this study. The correlation between the PMR-ASs was excellent, as the ICC and kappa were >0.85 from week 4 until week 24 (CRP-PMR-AS ≤10 or >10). Bland-Altman plots revealed that the differences between the CRP-PMR-AS and the other threescores were low. The cut-off values for the clin-PMR-AS were similar to those for the CRP-PMR-AS 86% of the time. CONCLUSION: The correlation between all the PMR-ASs was excellent, reflecting the low weight of CRP. In clinical trials using drugs that have an impact on CRP, the derived activity scores can be used. TRIAL REGISTRATION NUMBER: NTC02908217.

The usefulness of 18F-FDG-PET/CT in detecting musculoskeletal and vascular involvement in patients with polymyalgia rheumatica receiving glucocorticoids.

OBJECTIVE: Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT is a promising diagnostic tool for polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV). PET/CT performance is recommended before the onset of steroid therapy because glucocorticoids (GC) may decrease the intensity of FDG uptake. However, this is not always possible in clinical practice. Our aim was to assess if PET/CT could be also useful to detect musculoskeletal and vascular involvement in patients receiving GC. METHODS: Single-center study of patients with PMR diagnosis based on 2012 EULAR/ACR criteria who underwent a PET/CT scan due to LVV suspicion. We compared the musculoskeletal and vascular FDG uptake between two groups: (a) steroid-naïve and (b) steroid-resistant patients. A sub-analysis was conducted in patients who were receiving GC to discern if the cumulative prednisone dose influences the FDG uptake. RESULTS: We evaluated 75 patients (27 men/ 48 women); mean age±SD: 68.2 ± 10.7 years. PET/CT was performed in 14 steroid-naïve and 61 steroid-resistant patients. Patients under GC had received a median cumulative prednisone dose of 1.8 [0.6-3.9] g. The pattern of musculoskeletal FDG uptake was similar in steroid-naïve and steroid-resistant patients. FDG uptake in the vessel wall was more frequently detected in steroid-naïve patients. However, PET/ CT was also useful to detect LVV in 62.3 % of the patients who were receiving GC. The percentage of patients who had positive PET/CT scans tended to decrease with higher cumulative prednisone doses. CONCLUSION: Even though GC therapy may decrease the 18-FDG uptake, PET/CT continues to be a useful tool to detect musculoskeletal and LVV involvement in PMR.

[Polymyalgia rheumatica-A challenge in geriatrics : Interdisciplinary presentation of diagnostics and treatment]. / Polymyalgia rheumatica ­ eine Herausforderung in der Altersmedizin : Diagnostik und Therapie interdisziplinär dargestellt.

Polymyalgia rheumatica is the second most frequent inflammatory rheumatic disease in people aged over 50 years, after rheumatoid arthritis. It is characterized by pain and morning stiffness in the region of the shoulders, hip girdle and neck. It can be associated with giant cell arteritis (CGA). Treatment with glucocorticoids is indispensable. The duration of treatment varies and often exceeds 1 year. The additive administration of methotrexate is an option for saving glucocorticoids. The biologicals tocilizumab or secukinumab are very promising alternatives. The course of treatment should be closely monitored for inflammation parameters, glucocorticoid side effects, pain, visual acuity, depression, activities of daily living and especially related to functions of the upper extremities. The geriatric assessment plays an important role in the management of this condition.

Review of phase 2/3 trials in polymyalgia rheumatica and giant cell arteritis.

INTRODUCTION: GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) are two overlapping inflammatory rheumatic conditions that are seen exclusively in older adults, sharing some common features. GCA is a clinical syndrome characterized by inflammation of the medium and large arteries, with both cranial and extracranial symptoms. PMR is a clinical syndrome characterized by stiffness in the neck, shoulder, and pelvic girdle muscles. Both are associated with constitutional symptoms. AREAS COVERED: In this review, we assess the established and upcoming treatments for GCA and PMR. We review the current treatment landscape, completed trials, and upcoming trials in these conditions, to identify new and promising therapies. EXPERT OPINION: Early use of glucocorticoids (GC) remains integral to the immediate management of PMR and GCA but being aware of patient co-morbidities that may influence treatment toxicity is paramount. As such GC sparing agents are required in the treatment of PMR. Currently there are limited treatment options available for PMR and GCA, and significant unmet needs remain. Newer mechanisms of action, and hence therapeutic options being studied include CD4 T cell co-stimulation blockade, IL-17 inhibition, IL-12/23 inhibition, GM-CSF inhibition, IL-1ß inhibition, TNF-α antagonist and Jak inhibition, among others, which will be discussed in this review.

Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases?

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.

Evidence on treat to target strategies in polymyalgia rheumatica and giant cell arteritis: a systematic literature review.

OBJECTIVES: To inform an international task force about current evidence on Treat to Target (T2T) strategies in PMR and GCA. METHODS: A systematic literature research (SLR) was conducted in Medline, EMBASE, Cochrane Library, clinicaltrials.gov from their inception date to May 2022, and in the EULAR/ACR abstract database (2019-2021). Randomised clinical trials (RCTs) and non-randomised interventional studies published in English and answering at least one of the eleven PICO questions on T2T strategies, treatment targets and outcomes, framed by the taskforce, were identified. Study selection process, data extraction and risk of bias assessment were conducted independently by two investigators. RESULTS: Of 7809 screened abstracts, 397 were selected for detailed review and 76 manuscripts were finally included (31 RCTs, eight subgroup/exploratory analyses of RCTs and 37 non-randomised interventional studies). No study comparing a T2T strategy against standard of care was identified. In PMR RCTs, the most frequently applied outcomes concerned treatment (90.9% of RCTs), particularly the cumulative glucocorticoids (GC) dose and GC tapering, followed by clinical, laboratory and safety outcomes (63.3% each). Conversely, the most commonly reported outcomes in RCTs in GCA were prevention of relapses (72.2%), remission as well as treatment-related and safety outcomes (67.0% each). CONCLUSIONS: This SLR provides evidence and highlights the knowledge gaps on T2T strategies in PMR and GCA, informing the task force developing T2T recommendations for these diseases.

Treatment of Polymyalgia Rheumatica by Rheumatology Providers: Analysis from the American College of Rheumatology RISE Registry.

OBJECTIVE: This study describes the demographics, comorbidities, and treatment patterns in a national cohort of patients with polymyalgia rheumatica (PMR) who received care from rheumatology providers. METHODS: Patients with PMR were identified in the American College of Rheumatology Rheumatology Informatics System for Effectiveness registry from 2016 to 2022. Use of glucocorticoids and immunomodulatory antirheumatic medications used as steroid-sparing agents were examined overall and in a subgroup of patients new to rheumatology practices, the majority with presumed new-onset PMR. In these new patients, multivariate logistic regressions were performed to identify factors associated with persistent glucocorticoid and steroid-sparing agent use at 12 to 24 months. RESULTS: A total of 26,102 patients with PMR were identified, of which 16,703 new patients were included in the main analysis. Patients were predominantly female (55.8%) and White (46.7%), with a mean age of 72.0 years. Hypertension (81.2%), congestive heart failure (52.4%), hyperlipidemia (41.3%), and ischemic heart disease (36.0%) were the most prevalent comorbidities. At baseline, 92.3% of patients were on glucocorticoids, and only 13.1% were on a steroid-sparing agent. At 12 to 24 months, most patients remained on glucocorticoids (63.8%). Although there was an increase in use through follow-up, antirheumatic medications were prescribed only to a minority (39.0%) of patients with PMR. CONCLUSION: In this large US-based study of patients with PMR receiving rheumatology care, only a minority of patients were prescribed steroid-sparing agents during the first 24 months of follow-up; most patients remained on glucocorticoids past one year. Further identification of patients who would benefit from steroid-sparing agents and the timing of steroid-sparing agent initiation is needed.

Risk Factors for Relapse and/or Prolonged Glucocorticoid Therapy in Polymyalgia Rheumatica: Multicenter Study in 185 Patients.

BACKGROUND: In polymyalgia rheumatica (PMR) relapses and long-term GC dependency are common. We assessed risk factors for higher relapse rate and/or prolonged glucocorticoid therapy in PMR patients. METHODS: A multicenter and observational study (chart review) of PMR patients seen between 2006 and 2021 who had at least a 3-month follow-up period after starting GCs was performed. Results were expressed as median and interquartile range 25th-75th or mean ± standard deviation for numerical variables and percentage for categorical ones. Relapse versus nonrelapse groups were compared using Cox proportional analysis. Hazards ratios (HRs) with 95% confidence intervals (CIs) are reported. In all cases, a p value <0.05 was considered to indicate statistical significance. RESULTS: We included 185 patients (69.1% female). The median follow-up time was 17.1 months (interquartile range, 6.8-34.7). Incidence of relapses was 1.2 per 100 persons/month. In univariate analysis, PMR patients with a previous history of dyslipidemia had a lower risk of relapse (HR, 0.55; 95% CI, 0.33-0.94; p = 0.03); high-dose GC (HR, 2.35; 95% CI, 1.42-3.87; p = 0.001) and faster GC dose reduction had higher risk of relapse (HR, 3.04; 95% CI, 1.77-5.21; p = 0.001). In multivariate analysis, a previous history of dyslipidemia had a lower risk of relapse (HR, 0.54; 95% CI, 0.32-0.92; p = 0.023), and high dose of GC (HR, 2.46; 95% CI, 1.49-4.08; p = 0.001) remained the only risk factors for relapse. CONCLUSIONS: Lower doses of corticosteroids and a slow rate of reduction are critical to avoid relapse in PMR. Risk factors for higher relapse rate rely on therapy more than clinical characteristics of the patients at the time of diagnosis of PMR.

Combining immune-checkpoint inhibitors with tocilizumab to treat a lung adenocarcinoma patient with pre-existing polymyalgia rheumatica: A case report.

Immune-checkpoint inhibitors (ICIs) have changed the management of advanced cancers. However, patients with pre-existing autoimmune diseases (ADs) have usually been excluded from clinical trials of ICIs due to concerns about exacerbation of AD. Here, we combined ICIs with selective immunosuppressant treatment in a metastatic lung adenocarcinoma patient with active pre-existing polymyalgia rheumatica (PMR). Remarkably, the strategy led to durable response and no exacerbation of PMR. Thus, we provide the first clinical evidence of treating metastatic cancer with ICIs and concomitant use of tocilizumab and hydroxychloroquine for active pre-existing PMR.