Biological therapy in polymyalgia rheumatica.

INTRODUCTION: Polymyalgia rheumatica (PMR) is an inflammatory rheumatic disease of the elderly, treated mainly with systemic corticosteroids. The frequency of side effects of steroids is high in this aged population and increased due to comorbidities. The use of biological treatments could be of interest in this condition. AREAS COVERED: This review takes into account literature data from the PubMed and clinical trial databases concerning the results of the use of biological treatments in PMR, in terms of efficacy and safety of these treatments. EXPERT OPINION: Current data do not allow us to identify any particular efficacy of the various anti-TNF agents used in the treatment of PMR. Anti-interleukin 6 agents (tocilizumab, sarilumab) have shown consistent efficacy results, suggesting a particularly interesting steroid-sparing effect in the population under consideration. The safety profile appears acceptable. Other biologic targeted treatments are currently being evaluated. Anti-interleukin-6 agents may well have a place in the therapeutic strategy for PMR, particularly for patients with steroid-resistant disease or at high risk of complications of corticosteroid therapy.

Giant cell arteritis: a cause of temporomandibular joint claudication.

The purpose of this case report was to benefit the clinical recognition and conservative management of giant cell arteritis (GCA) in temporal arteries associated with jaw claudication. Giant cell arteritis is a systemic inflammatory vasculitis that affects medium-to-large-sized arteries. Primarily affecting arteries in heads, especially in temples, chronic GCA can result in secondary headaches and even polymyalgia rheumatica. This is a case report of a 68-year-old female with a 10-year history of GCA. The patient presented jaw claudication, headache, and joint stiffness over 6 months. The left palpable superficial temporal artery was thickened and tendered. A full-spine radiograph revealed uneven shoulders, imbalanced jaws, and moderate lumbar scoliosis. After nine months with conservative management, the patient was completely recovered from the symptoms with significantly improved radiographic parameters. Patients with GCA can present with jaw claudication. Physiotherapy and chiropractic collaborations are options for patients with GCA who suffer from the chronic adverse effect of medicines. Clinicians should be aware of the common clinical findings associated with GCA when rehabilitation treatment is planned.

Glucocorticoids Are Not Associated with Bone Mineral Density in Patients with Polymyalgia Rheumatica, Giant Cell Arteritis and Other Vasculitides-Cross-Sectional Baseline Analysis of the Prospective Rh-GIOP Cohort.

BACKGROUND: Glucocorticoids (GCs) can cause osteoporosis (OP). Prior observational research on bone density and the effects of GCs in polymyalgia rheumatica (PMR) and vasculitides is scarce and inconclusive. METHODS: Rh-GIOP is a prospective cohort study of bone health in patients with inflammatory rheumatic diseases. In this cross-sectional baseline analysis, we focused on patients with PMR and different forms of vasculitides. Multivariable linear regression was used to model the effect of current and cumulative GC intake on the minimum T-score at any site (mTs; at either lumbar spine or hip), with comprehensive adjustment for confounders. In separate models, GCs were modelled both as continuous and categorical predictors. Sensitivity analyses, stratifying by measurement site and disease, were conducted. RESULTS: A total of 198 patients, with a mean age of 67.7 ± 11.4 years and a mean disease duration of 5.3 ± 6.3 years, were included. Most patients suffered from PMR (36%), giant cell arteritis (26%) or granulomatosis with polyangiitis (17%). Women comprised 66.7% of the patients, and 87.4% were currently taking GCs. The mean CRP was 13.2 ± 26.1 mg/L. OP diagnosed by dual energy X-ray absorptiometry (DXA) (T-score ≤ -2.5) was present in 19.7% of the patients. While 88% were taking vitamin D supplements, calcium supplementation (4%) and treatment with anti-resorptive agents (17%) were relatively infrequent. Only 7% had a vitamin D deficit. Neither current (ß(continuous model) = -0.01, 97.5% CI -0.02 to 0.01; p(all models) ≥ 0.49) nor cumulative (ß(continuous model) = 0.01, 97.5% CI -0.04 to 0.07; p(all models) ≥ 0.35) GC doses were associated with mTs in any model. CRP was not associated with mTs in any model (p(all models) ≥ 0.56), and no interaction between CRP and GC intake was observed (p for interaction(all models) ≥ 0.32). Across all analyses, lower body mass index (p(all models) ≤ 0.01), history of vertebral fractures (p(all models) ≤ 0.02) and proton-pump inhibitor intake (p(all models) ≤ 0.04) were associated with bone loss. Sensitivity analyses with femoral neck and lumbar spine T-scores as dependent variables led to similar results as the analysis that excluded patients with PMR. CONCLUSIONS: In this cohort of PMR and vasculitides, we found a similar prevalence of OP by DXA to the overall elderly German population. Vitamin D supplementation was very common, and vitamin D insufficiency was less frequent than expected in Germans. There was no association between current or cumulative GC intake, CRP and impaired bone density. Proton-pump inhibitors seem to be a major, but somewhat neglected, risk factor for OP and should be given more attention. Our findings require confirmation from longitudinal analyses of the Rh-GIOP and other cohorts.

What non-pharmacological treatments do people with polymyalgia rheumatica try: results from the PMR Cohort Study.

Polymyalgia rheumatica (PMR) is common. The mainstay of treatment, glucocorticoids, are associated with significant adverse effects and many patients remain on high doses for a number of years. Little is known about the use of other, non-pharmacological therapies as adjuncts in PMR. The PMR Cohort Study is an inception cohort study of patients diagnosed with PMR in primary care. This analysis presents data on the use and perceived impact of non-pharmacological therapies from a long-term follow-up survey. Non-pharmacological treatments were classified as either diet, exercise, or complementary therapies. Results are presented as adjusted means, medians, and raw counts where appropriate. One hundred and ninety-seven participants completed the long-term follow-up questionnaire, of these 81 (41.1%) reported using non-pharmacological therapy. Fifty-seven people reported using a form of complementary therapy, 35 used exercise and 20 reported changing their diet. No individual non-pharmacological therapy appeared to be associated with long-term outcomes. The use of non-pharmacological therapies is common amongst PMR patients, despite the paucity of evidence supporting their use. This suggests that people perceive a need for treatment options in addition to standard glucocorticoid regimens. Further research is needed to understand patients' aims when seeking additional treatments and to strengthen the evidence base for their use so that patients can be guided towards effective options.

Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults.

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.

Trabecular Bone Score Is a Useful Parameter for the Prediction of Vertebral Fractures in Patients With Polymyalgia Rheumatica.

INTRODUCTION: Polymyalgia rheumatica (PMR), a benign rheumatic disorder, requires long-term glucocorticoid therapy, which could be associated with osteoporosis. In the present study, we compared bone mineral density (BMD), trabecular bone score (TBS) and frequencies of vertebral fracture (VF) among patients with PMR or rheumatoid arthritis (RA) and controls. METHODS: Fifty-three postmenopausal women with PMR aged 50 yr or older were eligible for inclusion in this study. Subjects in RA (n = 106) and control (n = 106) groups were selected by propensity score matching with controlling age, body mass index and use of anti-osteoporotic agents. RESULTS: The frequency of VF in patients with PMR (30.2%) was significantly higher than those in patients with RA (13.2 %) and controls (13.2%, p = 0.017). The mean TBS of patients with PMR (1.317 ± 0.092) was significantly lower than those of patients with RA (1.336 ± 0.089) and the controls (1.373 ± 0.073, p < 0.001). In receiver operating characteristic analysis for VF in patients with PMR, the area under the curve (AUC) was 0.759 (95% confidence interval [CI] = 0.601-0.918, p < 0.001) for TBS and 0.618 (95% CI = 0.442-0.795, p < 0.001) for L-spine BMD. The AUCs were 0.760 (95% CI = 0.630-0.891, p ≤ 0.001) and 0.767 (95% CI 0.627-0.907, p < 0.001) for femur neck and total hip BMD, respectively. Multivariate analysis identified the factor associated with VF of patients with PMR as a lower TBS (Odds ratio: 0.000, 95% CI: 0.000, 0.754, p = 0.043). CONCLUSION: TBS could be a supplementary tool for discriminating osteoporotic fractures in postmenopausal patients with PMR.

[Clinical experience of professor WANG Ju-yi in channel palpation treatment for polymyalgia rheumatica].

Professor WANG Ju-yi has gradually improved the clinical application of channel palpation treatment based on his more than 50 years clinical practice, and has accumulated rich experience in acupuncture treatment of polymyalgia rheumatica. He believes that "wind, cold and dampness" are the external causes of the disease, physical factors, uncomfortable mood and uncontrolled diet are the internal causes. The meridian-collateral theory is utilized in the diagnosis and detection of the disorders of taiyin, taiyang and jueyin meridians, internal and external causes are solved by expelling the wind, warming the channel to eliminate the coldness, transforming the dampness to relieve pain and regulating the qi activity. Three cases of clinical application on polymyalgia rheumatica were included in this paper.

Clinical experience of professor - in channel palpation treatment for polymyalgia rheumatica / 中国针灸

Professor - has gradually improved the clinical application of channel palpation treatment based on his more than 50 years clinical practice, and has accumulated rich experience in acupuncture treatment of polymyalgia rheumatica. He believes that "wind, cold and dampness" are the external causes of the disease, physical factors, uncomfortable mood and uncontrolled diet are the internal causes. The meridian-collateral theory is utilized in the diagnosis and detection of the disorders of , and meridians, internal and external causes are solved by expelling the wind, warming the channel to eliminate the coldness, transforming the dampness to relieve pain and regulating the activity. Three cases of clinical application on polymyalgia rheumatica were included in this paper.

[Off-label biological therapies in patients with large vessel vasculitis and/or polymyalgia rheumatica : Safety and efficacy analysis of a nationwide German registry (GRAID2)]. / Off-label-Biologikatherapie bei Patienten mit Großgefäßvaskulitiden und/oder Polymyalgia rheumatica : Wirksamkeits- und Sicherheitsanalyse eines nationalen Registers (GRAID2).

OBJECTIVE: To evaluate the safety and clinical outcome of biological therapies in patients with large vessel vasculitis (LVV) or polymyalgia rheumatica (PMR) refractory to standard of care therapy in a real-life setting in Germany. METHODS: GRAID 2 (German Registry in Autoimmune Diseases 2) is a retrospective, noninterventional, multicenter registry collecting data from all patients with inflammatory rheumatic diseases refractory to conventional therapy treated with an initial off-label biological between August 2006 and December 2013. The retrospective documentation comprised case history, diagnosis, course of disease including safety and overall efficacy. RESULTS: Data from 14 patients were collected, 11 with LVV (78.6%) and 3 with isolated PMR (21.4%). Ten patients were treated with tocilizumab (71.4%), while 3 patients received infliximab infusions (21.4%) and 1 patient was treated with rituximab (7.1%). All clinical as well as laboratory efficacy parameters improved substantially. After the first application, tolerability of biologicals was assessed as "very good"/"good" by the physicians in 92.3% of the patients. Altogether, 8 adverse events (AEs) occurred in 4 patients including 3 infections (1 urogenital infection, 2 diverticulitis) representing a rate of 23.6 infections per 100 patient-years. One of these infections (diverticulitis under infliximab treatment) was rated as serious AE, requiring ICU treatment representing a rate of serious AEs of 7.9 per 100 patient-years. No deaths occurred during the observation period. CONCLUSION: With known limitations of a retrospective database, the results of this survey confirm data of smaller case series and proof-of-concept studies and suggest a substantial response to biological therapies in patients with otherwise refractory LVV or PMR with no new safety signals.

Sustained remission after long-term biological therapy in patients with large vessel vasculitis: an analysis of ten cases / Remisión sostenida tras terapia biológica en pacientes con vasculitis de grandes vasos: análisis de 10 casos

Objectives. To describe the results obtained in clinical practice with the use of biological therapy (BT) in patients diagnosed with Takayasu arteritis (TA) and giant cell arteritis (GCA). Methods. Retrospective single center study of TA/GCA patients who received BT (infliximab [IFX], etanercept [ETN] and tocilizumab [TCZ]). In TA, active disease was defined according to a previous National Institutes of Health study. In GCA, active disease was defined with a modified criteria and clinical manifestations secondary to temporal artery involvement or polymyalgia rheumatica symptoms. Clinical data and outcomes are reported using descriptive statistics. Results. Five patients with TA and 5 with GCA were included. The main reason for starting BT was lack of response to prior therapy and/or ≥2 relapses during GC tapering. Five patients started IFX, four TCZ and 1 ETN. Remission was observed before 6 months in all cases. Only one patient had a relapse during long-term follow-up and the overall GC daily dose was reduced by 70%. Two AEs were considered attributable to IFX and one to TCZ. Conclusion. A favorable and sustained response to BT was observed in our patients with TA and GCA. Thus, BT might be considered as an alternative in patients with large vessel arteritis refractory to conventional treatment or with GC related comorbidities (AU)

Objetivos. Describir los resultados obtenidos en la práctica clínica diaria con el uso de la terapia biológica (TB) en pacientes con diagnóstico de arteritis de Takayasu (AT) y arteritis de células gigantes (ACG). Métodos. Estudio retrospectivo monocéntrico de pacientes con AT/ACG que recibieron TB (infliximab, etanercept y tocilizumab). En AT, la enfermedad activa se definió de acuerdo a un estudio previo del National Institutes of Health. En ACG, la enfermedad activa se definió con dichos criterios modificados y manifestaciones clínicas secundarias a afectación de la arteria temporal o síntomas de polimialgia reumática. Los datos y los desenlaces clínicos se muestran mediante estadística descriptiva. Resultados. Se incluyeron 5 pacientes con AT y 5 con ACG. La razón principal para el inicio de la TB fue la falta de respuesta al tratamiento previo y/o ≥2 recaídas durante la terapia con corticoides. Cinco pacientes comenzaron infliximab, 4 tocilizumab y uno etanercept. La remisión se observó antes de los 6 meses en todos los casos. Solo un paciente tuvo una recaída durante el seguimiento a largo plazo. La dosis diaria de corticoides se redujo globalmente en un 70%. Dos acontecimientos adversos se consideraron atribuibles a infliximab y uno a tocilizumab. Conclusión. Se observó una respuesta favorable y sostenida a la TB en nuestros pacientes con AT y ACG. Por lo tanto, la TB puede ser considerada una alternativa en pacientes refractarios al tratamiento convencional o con comorbilidades asociadas a los corticoides (AU)

Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study.

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

Circadian variations in clinical symptoms and concentrations of inflammatory cytokines, melatonin, and cortisol in polymyalgia rheumatica before and during prednisolone treatment: a controlled, observational, clinical experimental study.

BACKGROUND: In contrast to rheumatoid arthritis (RA), no systematic investigation of diurnal variation has been carried out in polymyalgia rheumatica (PMR). The aim of the study was to provide the often-requested documentation of the 24-h time course of clinical symptoms in PMR and relate them to concentrations during the day of melatonin, inflammatory cytokines, and cortisol. Furthermore, the effects of 14 days of prednisolone treatment were studied. METHODS: Ten glucocorticoid-naive patients newly diagnosed with PMR and seven non-PMR control subjects were studied for 24 h before treatment and during the 14th day of treatment with 20 mg/day of prednisolone. Global pain and generalized muscle stiffness were monitored by using visual analogue scales, and blood was drawn repeatedly. RESULTS: In untreated patients, pain and stiffness peaked in the early morning, showing a plateau between 04:00 and 08:00, and then declined to a nadir at 16:00 (2P < 0.05). Plasma concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, IL-1ß, and IL-4 varied with time in both groups (2P < 0.05) and peaked between 04:00 and 08:00. Furthermore, except for IL-1ß, concentrations of these cytokines and of IL-10 were higher throughout the 24-h observation period in patients than in control subjects (2P < 0.05). Also, melatonin and cortisol were consistently higher in patients (2P < 0.05) and varied with time (2P < 0.05), peaking around 02:00 and 08:00, respectively. In patients, prednisolone abolished symptoms, normalized C-reactive protein, and reduced melatonin, IL-6, IL-8, and TNF-α concentrations (2P < 0.05), while IL-10 increased between 10:00 and 14:00. CONCLUSIONS: In PMR, key symptoms show diurnal variation. Furthermore, in PMR, concentrations of melatonin, several pro- and anti-inflammatory cytokines, and cortisol are increased throughout the day and show diurnal variation, as also seen in healthy subjects. The time courses and the inhibitory effects of prednisolone indicate that in PMR, as proposed for RA, melatonin stimulates cytokine production, which in turn accounts at least partly for the symptoms. Furthermore, overall, cortisol may downregulate cytokine production and symptoms. Stimulation of IL-10 secretion may participate in the anti-inflammatory effects of prednisolone. These findings support use of chronotherapy in PMR and encourage study of circadian variations in other inflammatory autoimmune diseases.

[Polymyalgia rheumatica update, 2015]. / Polymyalgia rheumatica update, 2015.

Polymyalgia rheumatica is an inflammatory musculoskeletal disorder of people aged 50 years or over, characterised by pain, aching and morning stiffness in the shoulder girdle and often hip girdle and neck. Marked systemic inflammation and rapid response to corticosteroid therapy are characteristic features. Giant cell arteritis is a well-known association of polymyalgia rheumatica. Recent clinical evidence and scientific results in the field have provided new challenges for rheumatologists. Besides the aspecific - although characteristic - proximal syndrome, less well recognizable and more variable distal musculoskeletal manifestations were observed. Magnetic resonance and ultrasound studies showed mild, remitting and non-erosive synovitis, with dominating inflammation of the extraarticular synovial structures. As no pathognostic sign is known, the diagnosis of polymyalgia rheumatica is based on its differential diagnosis, differentiation from the polymyalgia mimics; particularly from elderly onset inflammatory arthritides, such as elderly onset rheumatoid arthritis and late onset seronegative spondylarthritis. In 2012 the international polymyalgia rheumatica work group under the guidance of the American College of Rheumatology and European League Against Rheumatism elaborated new classification criteria, the scoring algorythm of which is based on clinical symptoms, with ultrasonography increasing the specificity. Corticosteroids remain the cornerstone of the therapy of polymyalgia rheumatica. No effective steroid-sparing drug has been found to date. Corticosteroids are generally needed for 1-1.5 years, though some patients have a chronic-relapsing course and require corticosteroids for several years. Well known corticosteroid-related side effects (diabetes, hypertension, hyperlipidaemia and osteoporosis) cause significant morbidity and economic burden on the society. Novel therapeautic approaches are on trial. Early recognition of the disease, early start of corticosteroids and a well-defined course, prevention and management of side effects are everyday tasks for rheumatologists and family doctors. Knowledge of polymyalgia rheumatica is essential for all medical specialties.

Glucocorticoid-resistant polymyalgia rheumatica: pretreatment characteristics and tocilizumab therapy.

Treatment with glucocorticoid (GC) is the preferred therapy for polymyalgia rheumatica (PMR), but some patients show poor responses to the initial GC regimen or experience flares on GC tapering. Alternative therapies for patients with GC resistance have not yet been established. To evaluate pretreatment characteristics and therapeutic outcomes of GC-resistant PMR, we followed all patients who had been diagnosed with PMR between October 2007 and February 2013, according to our standardized protocol. GC-resistant patients were defined as those who had responded poorly to the initial GC regimen (15 mg/day of prednisolone) or those who had responded to the initial regimen but had experienced a flare upon GC tapering to 5 mg/day of the maintenance dose or within the first 6 months of maintenance therapy. Out of 23 patients, nine were found to be GC-resistant cases and the others were GC responders. Baseline values of PMR activity score and its components, especially the ability to elevate the upper limbs (EUL), were significantly higher in GC-resistant patients compared with GC responders. The additional use of methotrexate (MTX, five cases), salazosulfapyridine (one case), and tocilizumab (TCZ, three cases) was effective for GC-resistant patients, although 13 to 39 weeks were required for the achievement of remission. We report the three GC-resistant cases in which TCZ was added to GC therapy with or without MTX. We also review the medical literature on the use of TCZ as of January 31, 2014 and discuss the utility of TCZ in the treatment of GC-resistant PMR.

2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative.

Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.

Polymyalgia rheumatica: strategies for efficient practice and quality assurance.

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in persons over the age of 50 years. There are many diseases which mimic PMR, for which reason a careful diagnostic approach is required. While it is thought to be exquisitely responsive to glucocorticosteroid therapy, many patients respond incompletely and/or develop serious side effects over the protracted disease course. Improved methods for classification and disease assessment together with standardized treatment approaches and outcome assessments can serve to improve the care of patients with this disease.

Vitamin D for the treatment of chronic painful conditions in adults.

BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the treatment of chronic painful conditions in adults'.Vitamin D is produced in the skin after exposure to sunlight and can be obtained through food. Vitamin D deficiency has been linked with a range of conditions, including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic painful conditions. OBJECTIVES: To assess the efficacy and safety of vitamin D supplementation in chronic painful conditions when tested against placebo or against active comparators. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by searching the reference lists of retrieved articles, reviews in the field, and online trial registries. SELECTION CRITERIA: We included studies if they were randomised double-blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic painful conditions in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. We did not undertake pooled analysis due to the heterogeneity of the data. Primary outcomes of interest were pain responder outcomes, and secondary outcomes were treatment group average pain outcomes and adverse events. MAIN RESULTS: We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co-interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was associated with greater efficacy than placebo in any chronic painful condition (low quality evidence). Adverse events and withdrawals were comparatively infrequent, with no consistent difference between vitamin D and placebo (good quality evidence). AUTHORS' CONCLUSIONS: The evidence addressing the use of vitamin D for chronic pain now contains more than twice as many studies and participants than were included in the original version of this review. Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.

Polymyalgia rheumatica: inflammation suppression with low dose of methylprednisolone or modified-release prednisone.

OBJECTIVE: Polymyalgia rheumatica (PMR) is an inflammatory disease that affects people aged > 50 years, and is characterised by pain and morning stiffness in the shoulder and pelvic girdle with synovitis of the proximal joints and extra-articular synovial structures. It is currently mainly treated with glucocorticoids (GCs). The aim of the study was to evaluate changes in inflammatory markers and their correlations with cortisol levels after treatment with 6-methylprednisolone (6-MP) or modified-release prednisone (MR-P) in patients with "early" PMR. PATIENTS AND METHODS: The study involved 81 GC-naïve with "early" PMR diagnosed on the basis of the 2012 EULAR/ACR criteria: 38 treated with 6-MP at a starting dose of 12 mg at 8.00 a.m, gradually tapered to 8, 4 and 2 mg/day, and 43 treated with MR-P at a starting dose of 10 mg at 10 p.m, tapered to 7, 5, 3, 2 and 1 mg. The markers of inflammation (ESR mm/h, CRP mg/dL and fibrinogen mg/dL), the circulating serum levels of cytokines (TNFa and IL-6), and morning serum cortisol levels were evaluated at baseline and during GC treatment. RESULTS: There were significant differences between baseline and the end of treatment in the serum levels of IL-6 (5.3 ± 9.3 vs 2.8 ± 3.3 pg/mL; p < 0.05) and CRP (2.1 ± 3.3 vs 0.9 ± 1.7 mg/dL; p < 0.01) in the patients treated with MR-P, and in serum cortisol levels (15.8±6.4 vs 13.6+5.6 µg/dL; p < 0.01) in the patients treated with 6-MP. After the first month of treatment, 76.7% of the patients treated with MR-P had IL6 levels at or below the upper normal limit, whereas 52.6% of those treated with 6-MP had normal IL6 levels (p < 0.05). There was also a significant difference in the percentage of patients in whom the daily GC dose was tapered within eight months (6.7% in the MR-P group vs 25% in the 6-MP group; p < 0.001) and, by the end of the study, respectively 59.5% vs 35.1% patients were receiving a low GC dose or had discontinued treatment altogether (OR 2.7, 95% CI 1.0-6.77; p < 0.001). After six and 12 months, respectively 10.3% and 14.3% of the patients had discontinued MR-P, as against none of the patients treated with 6-MP (p < 0.05). CONCLUSIONS: In this prospective observational study of PMR patients receiving low-dose GCs, the changes in inflammatory markers were similar in those treated with 6-MP or MR-P, whereas morning cortisol levels remained unchanged only in the MR-P group. During the first month of treatment, MR-P chronotherapy given at bedtime significantly decreased IL-6 levels. The percentage of patients stopping GC treatment was higher in the MR-P group than in the 6-MP group.