Recommendations for early referral of individuals with suspected polymyalgia rheumatica: An initiative from the international giant cell arteritis and polymyalgia rheumatica study group

Objective To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). Methods A task force including 29 rheumatologists/ internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1–5 scale) and agreement (LOA) (0–10 scale) were evaluated. Results Two overarching principles and five recommendations were developed. LOE was 4–5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. Conclusions These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR

Somatosensation in OA: exploring the relationships of pain sensitization, vibratory perception and spontaneous pain

Abstract Background Pain in osteoarthritis (OA) remains poorly understood. Different types of somatosensory alterations exist in OA including hyperesthesia and increased sensitivity to painful stimuli as well as those of decreased sensitivity to cutaneous stimuli including vibratory perception threshold. The relationship between these different somatosensory measures has not been previously evaluated in OA. In this observational study, we evaluated relationships between vibratory perception (VPT), pressure pain detection thresholds (PPT), allodynia and subjective pain in knee OA. Methods Forty-two persons with moderate to severe knee OA and 12 controls without OA were evaluated. VPT was measured using a biothesiometer. Allodynia was measured by application of a 60 g Von Frey monofilament repeatedly to predetermined sites. PPTs were measured using a pressure algometer. Results Increased vibratory acuity was associated with lower PPTs and presence of allodynia. Allodynia was more common in OA than controls (54.8% vs 16.6%, p = 0.024 in the ipsilateral knee, and 42.9% vs 0%, p = 0.005 in the contralateral knee). OA participants with allodynia had lower PPTs than those without allodynia. In those with OA, spontaneous knee pain was associated with lower PPTs and with allodynia. Conclusion This study confirms the presence of somatosensory alterations in OA. Sensory alterations (vibratory perception) were shown to be related to nociceptive alterations (sensitization) in OA, showing a general increased sensitivity to cutaneous mechanical stimulation. Understanding these relationships is an important step in delineating the complicated pathophysiology of pain processing in OA

Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial.

Peer reviewed: TrueAcknowledgements: The authors thank all the many study coordinators, investigators and patients involved for their valuable contributions. Jon Nilsen, PhD and Rachel Gurlin, PhD (Amgen), provided medical writing support for this manuscript.Funder: Amgen; FundRef: http://dx.doi.org/10.13039/100002429Funder: ChemoCentryxOBJECTIVES: To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial. METHODS: Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety. RESULTS: Of the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively. CONCLUSIONS: These data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab. TRIAL REGISTRATION NUMBER: NCT02994927

Efficacy and safety of avacopan in patients with ANCA-associated vasculitis receiving rituximab in a randomised trial.

To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial. Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety. Of the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively. These data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab. NCT02994927

Recommendations for early referral of individuals with suspected polymyalgia rheumatica: an initiative from the international giant cell arteritis and polymyalgia rheumatica study group

Objective: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR).Methods: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated.Results: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care.Conclusions: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.Keywords: Giant Cell Arteritis; Polymyalgia Rheumatica; Vasculitis