Results of a 1-year randomised double-blind placebo-controlled trial with methotrexate 25 mg/week in recently diagnosed polymyalgia rheumatica.

To evaluate the usefulness of the polymyalgia rheumatica (PMR) activity score (PMR-AS) in guiding adjustment of glucocorticoid (GC) dosage. Rheumatologists prospectively included patients receiving GC therapy for PMR. At each visit, they assessed disease activity using a visual analog scale for physician's global assessment (VASph) and recorded whether a flare was diagnosed and/or the GC dosage was changed. In each patient, the PMR-AS was calculated using the formula of Leeb and Bird: C-reactive protein (mg/dl) + VAS pain score (0 to 10) + VASph (0 to 10) + (morning stiffness in min × 0.1) + elevation of upper limbs (0-3). We evaluated the correlation between PMR-AS and GC dosage changes in the group already treated with GC. We included 89 patients (mean age 74.6 ± 6.2 yrs; disease duration 1.6 ± 2.2 yrs), who had a total of 149 visits. PMR-AS was available for 137 visits. Of those, 124 involved patients already treated with GC, and 13 patients who started GC treatment. The Spearman correlation coefficient between PMR-AS values and GC dosage change was 0.58 (p < 0.001). In the group already treated with GC, when the PMR-AS was higher than 20, GC dosages were never decreased. When the PMR-AS was between 10 and 20, GC dosages were decreased in 4 patients, unchanged in 4, and increased by < 5 mg in 4 patients. When PMR-AS was < 10, GC dosages were generally decreased. The PMR-AS is helpful for diagnosing flares of PMR and may also assist in everyday practice to decide how to change the GC dosage.

Background:Polymyalgia rheumatica (PMR) is a debilitating, immune-mediated, chronic inflammatory condition of unknown etiology. It is characterized by symmetrical pain and morning stiffness of the shoulders, neck, and pelvic girdle [1-2]....

<h3>Background</h3> Treatment with glucocorticoid (GC) is the preferred therapy for polymyalgia rheumatica (PMR), but half of the PMR patients experience a flare-up(s) of disease activity upon GC tapering or discontinuation....

BackgroundTreatment with glucocorticoid (GC) is the preferred therapy for polymyalgia rheumatica (PMR), but half of the PMR patients experience a flare-up(s) of disease activity upon GC tapering or discontinuation. In...

Background: Polymyalgia rheumatica (PMR) is the most common inflammatory disease in the elderly. The 2015 EULAR/ACR recommendations indicate that the management of PMR should be started with glucocorticoids (GCs) and if needed, followed by addition of methotrexate (MTX). The anti-interleukin-6 (IL-6) receptor antibody, tocilizumab (TCZ), has been shown to be effective for PMR. Objectives: To determine the efficacy and safety of TCZ in patients with refractory PMR who were resistant to or intolerant of GCs plus MTX and characterize the clinical profile of patients who need TCZ. Methods: Patients were diagnosed with PMR by the 2012 EULAR/ACR provisional classification criteria and treated according to the 2015 aCR/EULAR recommendations for the management of PMR. TCZ was further added to the patients who were GC plus MTX (GC/MTX)-resistant or -intolerant. The efficacy of treatment was determined by measuring the disease activity with PMR activity score (PMR-AS). We statistically analyzed the differences in clinical indicators between GC-responders, GC/MTX-responders, and GC/MTX-non-responders who need TCZ therapy. Results: Ninety-three patients (53 females and 40 males) were the average of 72.1 ± 9.4 years old, serum CRP 63 ± 42 mg/L, ESR 84 ± 34 mm/hr and blood platelet counts 331 ± 86 ×103/μl, at the first visit, and had been followed up for 25.4±19.6 months. All of them were treated first with prednisolone (PSL) (15.7± 4.3 mg/day). Relapses occurred in 43 patients (46.2%), at the PSL dose of 6.0 ± 5.6 mg/day, after 8.8 ± 6.7 month-GC treatment. GC was increased in 7 patients, and MTX (8.6 ± 2.9 mg/week) was added in 36 patients. Thirteen patients successfully discontinued GC, while 23 patients (24.7%) were resistant to or intolerant of GC/MTX. Ten of 23 patients agreed with TCZ therapy. Before TCZ addition, they were treated with PSL of 6.0 ± 2.2 mg/day plus MTX of 6.0 ± 3.8 mg/week, and serum CRP 9.7 ± 9 mg/L, blood platelet counts 271 ± 32 ×103/μl and PMR-AS 15.5 ±13.5. After 7.3 ± 4.2 month-TCZ treatment, PSL and MTX were reduced to 1.3 ± 1.6 mg/day and 2.2 ± 3.0 mg/week, and CRP, blood platelet counts and PMR-AS decreased to Conclusion: TCZ may provide a therapeutic option for patients with refractory PMR who were resistant to or intolerant of GC/MTX. Our retrospective results suggest that patients with severe PMR, who show thrombocytosis and need high dose GC for initial therapy, may be considered for early induction of TCZ. Disclosure of interests: None declared

Objective:To evaluate the validity and reliability of the polymyalgia rheumatica (PMR) activity score (PMR-AS) for relapse diagnosis by general practitioners (GPs) who manage a large proportion of patients with PMR.Methods:Seven...

BackgroundDetermination of disease activity in polymyalgia rheumatica (PMR) is challenging due to the subjective nature of symptoms and prevalence of concurrent musculoskeletal complaints in an elderly population. Traditionally the non...

1-year results of treatment with rituximab in polymyalgia rheumatica: an extension study of a randomised double-blind placebo-controlled trial.

To evaluate the use of (18)F-FDG PET/CT for the assessment of tocilizumab (TCZ) as first-line treatment in patients with polymyalgia rheumatica (PMR). Patients with PMR were prospectively enrolled in a multicentre clinical trial assessing TCZ therapy (the TENOR trial). The patients underwent FDG PET/CT at baseline, after the first infusion of TCZ (TCZ 1) and after the last infusion of TCZ (TCZ 3). Responses to treatment were evaluated in terms of the PMR activity score (PMR-AS), and the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) laboratory tests. Maximal standardized uptake value (SUVmax) was used for assessment of FDG uptake in regions usually affected in PMR (spinous processes, hips, shoulders, sternoclavicular region and ischial tuberosities). The Wilcoxon test was applied to evaluate the changes in parameters after the infusions and Spearman's rank correlation test was applied to assess the correlations between SUVmax and PMR-AS, CRP and ESR. Of 21 patients included in the trial, 18 were evaluated. The median bioclinical parameter values decreased after TCZ 1 (PMR-AS from 38.2 to 15.7, CRP from 65.2 to 0.4mg/l and ESR from 49 to 6.5mm; all p < 0.05) as did the median SUVmax (from 5.8 to 5.2; p < 0.05). All values also decreased after TCZ 3 (PMR-AS from 38.2 to 3.9, CRP from 65.2 to 0.2, ESR from 49 to 2, and SUVmax from 5.8 to 4.7; p < 0.05). In a region-based analysis, all SUVmax were significantly reduced after TCZ 3, except the values for the cervical spinous processes and shoulder regions. With regard to correlations, few significant differences were found between ∆SUVmax and the other parameters including ∆PMR-AS, ∆CRP and ∆ESR in the patient-based and region-based analysis. FDG uptake decreased significantly but moderately after TCZ therapy in PMR patients, and might reflect disease activity.

Methotrexate (MTX) is a well-known immunomodulator in the treatment of inflammatory bowel disease (IBD) and often combined with biological agents. The ideal MTX dose for combination therapy has not been determined. Our aim is to investigate the effect of varying doses of MTX when used with anti-TNF agents in IBD on efficacy and safety outcomes. This study included patients with Crohn’s disease (CD) or ulcerative colitis (UC) receiving care between January 2005 and June 2018. Low-dose MTX was defined as ≤15mg/week and high-dose as >15mg/week. The primary efficacy outcome was a composite of need for IBD-related hospitalization or surgery, steroid initiation, or change of biologic agent within 1 year. Safety outcomes included side effects related to MTX, serious infections, malignancy and need to discontinue MTX therapy within 1 year. Multivariable logistic regression models adjusting for relevant covariates examined the independent association between MTX dose and outcomes. Our study included 222 patients with IBD (163 CD, 59 UC). Just over half were receiving low dose MTX (51%). We found no difference in gender, IBD type, disease location and behavior, disease duration, prior IBD treatments, serum albumin and CRP between the two groups. The primary efficacy composite outcome was noted in 51 patients (47%) in the high dose MTX group compared to 47 patients (42%) in the low-dose MTX group (p=0.436). After adjusting for relevant confounders, there remained no difference in primary outcome between the two dose groups of MTX (OR 0.62, 95% CI 0.31 – 1.24, p=0.179). Separately, we also observed no difference in hospitalization, surgery or steroid initiation within 1 year between the low-dose and high-dose MTX groups (Figure 1). MTX dosage was not associated with likelihood of side effects (high dose 22.9% vs low dose 27.4%, p=0.44). A total of 20 serious infections (9%) were reported during the first year of combination therapy but there was no significant difference between high versus low dose MTX (9.2% vs. 8.9%, p=0.93). We found no significant associations with MTX dose and any side effect (OR 1.34, 95% CI 0.67 – 2.70, p=0.410) or development of serious infections (OR 0.97, 95% CI 0.35 – 2.67, p=0.946). Two cases developed a malignancy (thyroid carcinoma and hepatocellular carcinoma) during the first year of combination therapy, both in the high dose MTX group. Discontinuation of MTX therapy occurred in one fourth of the low dose MTX patients (24.8%) and 29.5% in patients with high dose MTX (p=0.442). Low dose and high dose MTX combination therapy were equally effective and no difference in infection and malignancy rates was observed. There is an important need for prospective trials comparing low and high dose MTX when used in combination with biologic therapy to determine optimal dosing. Figure 1. Comparison of safety (a) and efficacy (b) outcomes between low dose MTX and high dose MTX combination therapy

IntroductionTo elucidate in polymyalgia rheumatica (PMR) the role of tumor necrosis factor (TNF) α and the therapeutic potential of blockade with soluble TNF-α receptor, we carried out the first randomized controlled trial with etanercept in PMR.MethodsTwenty newly diagnosed, glucocorticoid (GC) naïve patients with PMR and 20 matched non-PMR control subjects completed the trial. Subjects were randomized in a 1:1 ratio to monotherapy with etanercept (25 mg s.c. biweekly) or placebo (saline) for 14 days. Study outcomes were assessed at baseline and after 14 days. The primary outcome was the change in PMR activity score (PMR-AS). Secondary outcomes were: changes in erythrocyte sedimentation rate (ESR) and plasma levels of TNF-α and interleukin (IL) 6; patients' functional status (health assessment questionnaire) and cumulative tramadol intake during the trial.ResultsAt baseline, plasma TNF-α was higher in patients than in controls (P < 0.05). The concentration always increased with etanercept treatment (P < 0.05). In patients, etanercept decreased PMR-AS by 24% (P = 0.011), reflecting significant improvements in shoulder mobility, physician's global assessment and C-reactive protein, and insignificant (P > 0.05) improvements in duration of morning stiffness and patient's assessment of pain. In parallel, ESR and IL-6 were reduced (P < 0.05). Placebo treatment did not change PMR-AS, ESR and IL-6 (P > 0.05). Functional status did not change and tramadol intake did not differ between patient groups. In controls, no changes occurred in both groups.ConclusionsEtanercept monotherapy ameliorates disease activity in GC naïve patients with PMR. However, the effect is modest, indicating a minor role of TNF-α in PMR.Trial registrationClinicalTrials.gov (NCT00524381).

Background. Immune checkpoint inhibitors (ICIs), widely used in cancer immunotherapy, can trigger immune-related adverse events, including polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), likely through mechanisms involving altered immune tolerance. We conducted a systematic review (SLR) and meta-analysis to characterize these conditions and explore potential differences from the idiopathic forms. Materials and Methods. The SLR analyzed Medline and EMBASE databases up to July 2024, comparing ICI-induced PMR and GCA to their primary forms. Where direct comparisons with idiopathic forms were unavailable, we referred to data from prior meta-analyses and large observational cohorts to qualitatively explore potential differences. Results. From 1,237 abstracts, 46 were included, yielding 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had a pooled prevalence of 0.3% [95% CI: 0.1%–1.2%] among ICI recipients. Patients were predominantly males (64% [95% CI: 54%–73%]), with a mean age of 71 years [95% CI: 68–74]. PD1/PDL1 blockers were used in 85% [95% CI: 80%–89%] of cases. Inflammatory pain in the girdles was universal (100%), however pelvic girdle involvement was explicitly reported in only 3 studies. Peripheral arthritis in ICI-PMR was present in 26% [95% CI: 9%–54%], and normal inflammatory markers were detected in 26% [95% CI: 15%–40%]. Glucocorticoids (GCs) completely improved symptoms in 83% of patients [95% CI: 66%–92%], with 13% [95% CI: 12%–34%] requiring DMARDs and 18% [95% CI: 9%–33%] experiencing relapses (Figure 1). Two comparative case-control studies showed significant differences between ICI-induced and primary PMR. ICI-PMR patients had milder symptoms, lower C-reactive protein levels, and required lower median prednisone dosages. ICI-GCA prevalence was 0.06% among ICI recipients. Male patients comprised 51% [95% CI: 36%–66%], with a mean age of 71 years [95% CI: 68–74]. About 50% [95% CI: 23%–77%] received anti-CTLA4 blockers (alone or with PD1 blockers), while the rest received PD1/PDL1 blockers. Clinical features included cephalic symptoms (85% [95% CI: 70%–93%]), permanent visual loss (23% [95% CI: 12%–39%]), and large-vessel involvement (62% [95% CI: 40%–80%]). No comparative studies between ICI-GCA vs primary GCA were retrieved. High-dose GCs permitted remission in 95% [95% CI: 73%–99%], though 19% [95% CI: 7%–41%] experienced relapses and 10% [2% - 31%] required DMARDs (Figure 1). Conclusions. ICI-induced PMR and GCA may differ from idiopathic forms, potentially presenting with milder symptoms and more favorable treatment responses. Large observational data and meta-analyses on primary forms suggest higher relapse rates and prolonged GC use [1,2], yet further robust comparative studies are needed to validate whether ICI-induced syndromes truly represent a distinct and less severe clinical entity.

We aimed to examine fatigue and sleep disturbance in patients with recently diagnosed polymyalgia rheumatica (PMR) compared to age- and gender-matched controls, including associated characteristics and change over an 18-month follow-up period. Patients meeting the 2012 European Alliance of Associations for Rheumatology/American College of Rheumatology classification criteria for PMR were prospectively recruited, together with matched controls. Assessments were undertaken 3 months after the commencement of glucocorticoids and again 18 months later. Fatigue was quantified using the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire and the 36-item Short Form Health Survey vitality scale. Sleep was quantified using the Pittsburgh Sleep Quality Index. Other data collected included PMR disease activity, depression, anxiety, and physical function status. All participants underwent body composition by dual-energy x-ray absorptiometry and physical function testing. Thirty-six participants with PMR and 32 controls were included. PMR disease activity was low at both visits. Significantly, more patients with PMR than controls suffered severe fatigue (PMR: 36% and 35% at baseline and follow-up, respectively; controls: 3% at both timepoints). Poor sleep quality also affected more patients with PMR (77% and 84% at baseline and follow-up, respectively) than controls (56% at both timepoints). Higher BMI and fat mass index, anxiety, depression, PMR Activity Score, inflammatory markers, pain, and stiffness were all associated with severe fatigue. There were no significant associations with poor sleep. Patients with PMR experience a disproportionate degree of fatigue and sleep disturbance, which persists almost 2 years after starting treatment. Features associated with fatigue include higher adiposity, psychological comorbidity, and PMR disease activity.

Abatacept in early polymyalgia rheumatica (ALORS): a proof-of-concept, randomised, placebo-controlled, parallel-group trial.

BackgroundGlucocorticoids are the cornerstone treatment of polymyalgia rheumatica (PMR) but induce adverse events.ObjectivesTo evaluate the efficacy and safety of first-line tocilizumab in PMR.MethodsIn a prospective open-label study (ClinicalTrials.gov: NCT01713842), 20...