EULAR recommendations for the non-pharmacological core management of hip and knee osteoarthritis: 2023 update.

INTRODUCTION: Hip and knee osteoarthritis (OA) are increasingly common with a significant impact on individuals and society. Non-pharmacological treatments are considered essential to reduce pain and improve function and quality of life. EULAR recommendations for the non-pharmacological core management of hip and knee OA were published in 2013. Given the large number of subsequent studies, an update is needed. METHODS: The Standardised Operating Procedures for EULAR recommendations were followed. A multidisciplinary Task Force with 25 members representing 14 European countries was established. The Task Force agreed on an updated search strategy of 11 research questions. The systematic literature review encompassed dates from 1 January 2012 to 27 May 2022. Retrieved evidence was discussed, updated recommendations were formulated, and research and educational agendas were developed. RESULTS: The revised recommendations include two overarching principles and eight evidence-based recommendations including (1) an individualised, multicomponent management plan; (2) information, education and self-management; (3) exercise with adequate tailoring of dosage and progression; (4) mode of exercise delivery; (5) maintenance of healthy weight and weight loss; (6) footwear, walking aids and assistive devices; (7) work-related advice and (8) behaviour change techniques to improve lifestyle. The mean level of agreement on the recommendations ranged between 9.2 and 9.8 (0-10 scale, 10=total agreement). The research agenda highlighted areas related to these interventions including adherence, uptake and impact on work. CONCLUSIONS: The 2023 updated recommendations were formulated based on research evidence and expert opinion to guide the optimal management of hip and knee OA.

Serum biomarkers in prednisolone-treated hand osteoarthritis patients.

OBJECTIVES: To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. METHODS: Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V collagen formation (PROC5), MMP-derived neoepitope of CRP (CRPM), citrullinated vimentin fragment (VICM), high-sensitivity (hsCRP)] were measured in sera from 78 patients with painful inflammatory hand OA, who were randomized between prednisolone or placebo treatment. Association of baseline biomarker levels with disease characteristics [visual analogue scale (VAS) pain, synovial thickening ultrasonography sum score and erosive OA] and OMERACT-Osteoarthritis Research Society International (OARSI) response after 6 weeks were analysed with linear or logistic regression and adjusted for age, BMI and sex. Change in biomarker levels after 6 weeks was assessed with linear regression adjusted for baseline biomarker levels, age, BMI and sex. RESULTS: For all patients (mean age 64 years, 79% female), there were no associations between biomarker levels and VAS finger pain or synovial thickening score at baseline. Patients with erosive hand OA had higher levels of C1M and hsCRP [adjusted geometric mean ratio 1.24 (95% CI 1.03, 1.49) and 1.91 (1.19, 3.06), respectively]. Biomarker levels did not decrease over time. There was no association between baseline biomarkers levels and OARSI response, except for CRPM [geometric mean ratio of 0.88 (0.77, 1.00)]. CONCLUSION: Erosive disease was associated with higher levels of C1M and hsCRP. Biomarker levels were not influenced by treatment with prednisolone. Current biomarkers were not associated with response to prednisolone in hand OA.

Risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in rheumatic and musculoskeletal diseases: a systematic literature review to inform EULAR recommendations.

OBJECTIVES: Perform a systematic literature review (SLR) on risk and prognosis of SARS-CoV-2 infection and vaccination against SARS-CoV-2 in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: Literature was searched up to 31 May 2021, including (randomised) controlled trials and observational studies with patients with RMD. Pending quality assessment, data extraction was performed and risk of bias (RoB) was assessed. Quality assessment required provision of (1) an appropriate COVID-19 case definition, and (2a) a base incidence (for incidence data) or (2b) a comparator, >10 cases with the outcome and risk estimates minimally adjusted for age, sex and comorbidities (for risk factor data). RESULTS: Of 5165 records, 208 were included, of which 90 passed quality assessment and data were extracted for incidence (n=42), risk factor (n=42) or vaccination (n=14). Most studies had unclear/high RoB. Generally, patients with RMDs do not face more risk of contracting SARS-CoV-2 (n=26 studies) or worse prognosis of COVID-19 (n=14) than individuals without RMDs. No consistent differences in risk of developing (severe) COVID-19 were found between different RMDs (n=19). Disease activity is associated with worse COVID-19 prognosis (n=2), possibly explaining the increased risk seen for glucocorticoid use (n=13). Rituximab is associated with worse COVID-19 prognosis (n=7) and possibly Janus kinase inhibitors (n=3). Vaccination is generally immunogenic, though antibody responses are lower than in controls. Vaccine immunogenicity is negatively associated with older age, rituximab and mycophenolate. CONCLUSION: This SLR informed the July 2021 update of the European Alliance of Associations for Rheumatology recommendations for the management of RMDs in the context of SARS-CoV-2.

EULAR recommendations for the management and vaccination of people with rheumatic and musculoskeletal diseases in the context of SARS-CoV-2: the November 2021 update.

The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway.EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR's standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.

Real-time vs static scoring in musculoskeletal ultrasonography in patients with inflammatory hand osteoarthritis.

OBJECTIVES: Agreement between real-time and static ultrasonography has not been studied in musculoskeletal diseases. We studied this agreement in inflammatory hand OA. METHODS: Ultrasonography was performed blinded to clinical information of 30 joints of 75 patients with hand OA, treated with prednisolone in a randomized placebo-controlled double-blind trial. Images were scored real-time at acquisition and stored images were scored static (paired in known chronological order) for inflammatory features and osteophytes (score 0-3). Agreement between methods was studied at joint level with quadratic weighted kappa. At patient level intra-class correlations (ICC) of sum scores and change in sum-scores (delta baseline-week 6) were calculated. Responsiveness of scoring methods was analysed with generalized estimating equations (GEE) with treatment as independent and ultrasonography findings as dependent variable. RESULTS: Agreement at baseline was good to excellent at joint level (kappa 0.72-0.88) and moderate to excellent at patient level (ICC 0.58-0.91). Agreement for change in sum scores was poor to fair for synovial thickening and effusion (ICC 0.18 and 0.34, respectively), while excellent for Doppler signal (ICC 0.80). Real-time ultrasonography discriminated between prednisolone and placebo with a mean between-group difference of synovial thickening of -2.5 (95% CI: -4.7, -0.3). Static ultrasonography did not show a decrease in synovial thickening. CONCLUSION: While cross-sectional agreement between real-time and static ultrasonography is good, static ultrasonography measurement of synovial thickening did not show responsiveness to prednisone therapy while real-time ultrasonography did. Therefore, when ultrasonography is used in clinical trials, real-time dynamic scoring should remain the standard for now.

Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation. METHODS: The HOPE study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands. Patients were considered eligible if they had symptomatic hand osteoarthritis and signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients were required to have four or more DIP/PIP joints with osteoarthritic nodes; at least one DIP/PIP joint with soft swelling or erythema; at least one DIP/PIP joint with a positive power Doppler signal or synovial thickening of at least grade 2 on ultrasound; and finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug (NSAID) washout (defined as worsening of finger pain by at least 20 mm on the VAS). Eligible patients were randomly assigned (1:1) to receive 10 mg prednisolone or placebo orally once daily for 6 weeks, followed by a 2-week tapering scheme, and a 6-week follow-up without study medication. The patients and study team were masked to treatment assignment. The primary endpoint was finger pain, assessed on a VAS, at 6 weeks in participants who had been randomly assigned to groups and attended the baseline visit. This study is registered with the Netherlands Trial Registry, number NTR5263. FINDINGS: We screened patients for enrolment between Dec 3, 2015, and May 31, 2018. Patients completed baseline visits and started treatment between Dec 14, 2015, and July 2, 2018, and the last study visit of the last patient was Oct 4, 2018. Of 149 patients assessed for eligibility, 57 (38%) patients were excluded (predominantly because they did not meet one or several inclusion criteria, most often because of an absence of synovial inflammation or of flare-ups after NSAID washout) and 92 (62%) patients were eligible for inclusion. We randomly assigned 46 (50%) patients to receive prednisolone and 46 (50%) patients to receive placebo, all of whom were included in the modified intention-to-treat analysis of the primary endpoint. 42 (91%) patients in the prednisolone group and 42 (91%) in the placebo group completed the 14-week study. The mean change between baseline and week 6 on VAS-reported finger pain was -21·5 (SD 21·7) in the prednisolone group and -5·2 (24·3) in the placebo group, with a mean between-group difference (of prednisolone vs placebo) of -16·5 (95% CI -26·1 to -6·9; p=0·0007). The number of non-serious adverse events was similar between the groups. Five serious adverse events were reported during our study: one serious adverse event in the prednisolone group (a myocardial infarction) and four serious adverse events in the placebo group (an infected traumatic leg haematoma that required surgery, bowel surgery, atrial fibrillation that required a pacemaker implantation, and symptomatic uterine myomas that required a hysterectomy). Four (4%) patients discontinued the study because of an adverse event: one (2%) patient receiving prednisolone (for a myocardial infarction) and three (7%) patients receiving placebo (for surgery of the bowel and for an infected leg haematoma and for Lyme disease arthritis of the knee). INTERPRETATION: Treatment with 10 mg prednisolone for 6 weeks is efficacious and safe for the treatment of patients with painful hand osteoarthritis and signs of inflammation. The results of our study provide clinicians with a new short-term treatment option for patients with hand osteoarthritis who report a flare-up of their disease. FUNDING: Dutch Arthritis Society.

Self-reported painful joint count and assessor-reported tender joint count as instruments to assess pain in hand osteoarthritis.

OBJECTIVES: To evaluate self-reported and assessor-reported joint counts for pain and their value in measuring pain and joint activity in hand OA patients. METHODS: A total of 524 patients marked painful joints on hand diagrams. Nurses assessed tenderness upon palpation. Pain was measured with a visual analogue scale pain and the Australian/Canadian hand OA index subscale pain. Synovitis and bone marrow lesions in right hand distal/proximal interphalangeal joints on MRI served as measure of joint activity. Agreement was assessed on the patient (intraclass correlation coefficient, Bland-Altman plot) and joint level (percentage absolute agreement). Correlations with measures of pain and joint activity were analysed, and joint level associations with synovitis/bone marrow lesions were calculated. RESULTS: Self-reported painful joint count (median 8, interquartile range 4-13) was consistently higher than assessor-reported tender joint count (3, 1-7). Agreement between patients and nurses on overall scores was low. Percentage absolute agreement on the joint level was 61-89%. Joint counts correlated similarly but weakly with measures of pain and joint activity (r = 0.14-0.38). On the joint level, assessor-reported tenderness was more strongly associated with synovitis/bone marrow lesions than self-reported pain. CONCLUSION: In hand OA, self- and assessor-reported joint counts cannot be used interchangeably, and measure other pain aspects than questionnaires. Assessor-reported tenderness was most closely related to MRI-defined joint activity.

Etanercept in patients with inflammatory hand osteoarthritis (EHOA): a multicentre, randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Hand osteoarthritis is a prevalent disease with limited treatment options. Since joint inflammation is often present, we investigated tumour necrosis factor (TNF) as treatment target in patients with proven joint inflammation in a proof-of-concept study. METHODS: This 1-year, double-blind, randomised, multicentre trial (NTR1192) enrolled patients with symptomatic erosive inflammatory hand osteoarthritis. Patients flaring after non-steroidal anti-inflammatory drug washout were randomised to etanercept (24 weeks 50 mg/week, thereafter 25 mg/week) or placebo. The primary outcome was Visual Analogue Scale (VAS) pain at 24 weeks. Secondary outcomes included clinical and imaging outcomes (radiographs scored using Ghent University Scoring System (GUSS, n=54) and MRIs (n=20)). RESULTS: Of 90 patients randomised to etanercept (n=45) or placebo (n=45), respectively, 12 and 10 discontinued prematurely. More patients on placebo discontinued due to inefficacy (6 vs 3), but fewer due to adverse effects (1 vs 6). The mean between-group difference (MD) in VAS pain was not statistically significantly different (-5.7 (95% CI -15.9 to 4.5), p=0.27 at 24 weeks; - 8.5 (95% CI -18.6 to 1.6), p=0.10 at 1 year; favouring etanercept). In prespecified per-protocol analyses of completers with pain and inflammation at baseline (n=61), MD was -11.8 (95% CI -23.0 to -0.5) (p=0.04) at 1 year. Etanercept-treated joints showed more radiographic remodelling (delta GUSS: MD 2.9 (95% CI 0.5 to 5.4), p=0.02) and less MRI bone marrow lesions (MD -0.22 (95% CI -0.35 to -0.09), p = 0.001); this was more pronounced in joints with baseline inflammation. CONCLUSION: Anti-TNF did not relieve pain effectively after 24 weeks in erosive osteoarthritis. Small subgroup analyses showed a signal for effects on subchondral bone in actively inflamed joints, but future studies to confirm this are warranted.

Validity, reliability, responsiveness and feasibility of four hand mobility measures in hand osteoarthritis.

OBJECTIVES: To investigate metric properties of four hand mobility tests in hand OA patients, using the OMERACT filter. METHODS: Trained assessors examined the Hand Mobility in Scleroderma test (HAMIS), fingertip-to-palm distance (FPD), modified Kapandji index (MKI) and number of hand joints with limited mobility in participants from two cohorts [Genetics ARthrosis and Progression (n = 207) and Hand OSTeoArthritis in Secondary care (n = 174)]. Validity was appraised by assessment of correlations with other outcome measures, and ability to measure thumb vs finger mobility specifically, using cumulative probability plots. The proportion of participants changing in hand mobility based on the smallest detectable difference was calculated for responsiveness. Intraclass correlation coefficients (ICCs) for intra- and interobserver reliability, and feasibility (time to perform tests) were studied in a random sample (n = 20). RESULTS: Participants displayed large variation in mobility scores. Strongest correlations were observed with structural damage (rs = 0.43-0.52) and bony swelling (rs = 0.46-0.58); correlation patterns were similar among tests. HAMIS, FPD and MKI could all measure finger mobility specifically, but only HAMIS measured thumb mobility particularly. Interobserver reliability was best for HAMIS, ICC 0.90 (95% CI: 0.76, 0.96); intraobserver reliability was excellent for all (ICCs 0.94-0.97). In 2 years, little change was observed; HAMIS was the most sensitive-to-change (smallest detectable difference 3.7% of maximum score). The mean performance time ranged from 0.7 (s.d. 0.5, for FPD) to 5.7 (s.d. 1.3, for HAMIS) min. CONCLUSION: HAMIS, FPD, MKI and number of joints with limited mobility are all valid, reliable and feasible measures for assessing hand mobility in hand OA, although HAMIS had slightly more favourable properties. Studies assessing sensitivity-to-change in a clinical trial setting are warranted.

TNF inhibitor treatment is associated with a lower risk of hand osteoarthritis progression in rheumatoid arthritis patients after 10 years.

Objective: To investigate the effect of TNF inhibitors (TNFis) on incidental and progressive hand OA in recent-onset RA patients after a 10 year follow-up. Methods: Radiographs of 262 RA patients (mean age 52 years, 66% women) from the BeSt study were scored for osteophytes in DIP/PIP joints using the Osteoarthritis Research Society International atlas (0-3; summed score 0-54) and according to the Kellgren-Lawrence (KL) score (0-4; summed score 0-72) at baseline and 10 year follow-up. TNFi treatment was assessed on visits every 3 months. Associations between TNFi treatment and hand OA were analysed on the patient and joint level using generalized linear models and generalized estimating equations, respectively. Results: Fifty-eight percent of the patients were treated with TNFi, with a median duration of 42 months. A total of 143 patients (55%) had hand OA in any IP joint at baseline based on the Osteoarthritis Research Society International osteophyte score. On the patient level, TNFi treatment duration did not affect incidental hand OA. However, every month of TNFi treatment resulted in a reduced relative risk (RR) of hand OA progression in DIP joints [relative risk (RR) 0.987 (95% CI 0.978, 0.996)] but not in PIP joints. On the joint level, the effect on hand OA progression was observed in DIP joints [RR 0.996 (95% CI 0.991, 1.000)] but not in PIP joints. The results from the KL score analyses were comparable to the osteophyte score. Conclusion: TNFi treatment was associated with a reduced risk on radiographic hand OA progression in DIP joints but not in PIP joints after 10 years. Although the effect sizes are small, these results provide evidence for influence of TNF-α in hand OA pathogenesis.

Reference curves for the Australian/Canadian Hand Osteoarthritis Index in the middle-aged Dutch population.

Objective: The aim was to establish reference curves of the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), a widely used questionnaire assessing hand complaints. Methods: Analyses were performed in a population-based sample, The Netherlands Epidemiology of Obesity study (n = 6671, aged 45-65 years). Factors associated with AUSCAN scores were analysed with ordered logistic regression, because AUSCAN data were zero inflated, dividing AUSCAN into three categories (0 vs 1-5 vs >5). Age- and sex-specific reference curves for the AUSCAN (range 0-60; higher is worse) were developed using quantile regression in conjunction with fractional polynomials. Observed scores in relevant subgroups were compared with the reference curves. Results: The median age was 56 [interquartile range (IQR): 50-61] years; 56% were women and 12% had hand OA according to ACR criteria. AUSCAN scores were low (median 1; IQR: 0-4). Reference curves where higher for women, and increased moderately with age: 95% percentiles for AUSCAN in men and women were, respectively, 5.0 and 12.3 points for a 45-year-old, and 15.2 and 33.6 points for a 65-year-old individual. Additional associated factors included hand OA, inflammatory rheumatic diseases, FM, socio-economic status and BMI. Median AUSCAN pain subscale scores of women with hand OA lay between the 75th and 90th centiles of the general population. Conclusion: AUSCAN scores in the middle-aged Dutch population were low overall, and higher in women than in men. AUSCAN reference curves could serve as a benchmark in research and clinical practice settings. However, the AUSCAN does not measure hand complaints specific for hand OA.

Non-steroidal anti-inflammatory drugs (NSAIDs) for axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis).

BACKGROUND: Axial spondyloarthritis (axSpA) comprises ankylosing spondylitis (radiographic axSpA) and non-radiographic (nr-)axSpA and is associated with psoriasis, uveitis and inflammatory bowel disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug treatment. OBJECTIVES: To determine the benefits and harms of NSAIDs in axSpA. SEARCH METHODS: We searched CENTRAL, MEDLINE and EMBASE to 18 June 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs of NSAIDs versus placebo or any comparator in adults with axSpA and observational cohort studies studying the long term effect (≥ six months) of NSAIDs on radiographic progression or adverse events (AEs). The main comparions were traditional or COX-2 NSAIDs versus placebo. The major outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), radiographic progression, number of withdrawals due to AEs and number of serious AEs DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed the risk of bias, extracted data and assessed the quality of evidence for major outcomes using GRADE. MAIN RESULTS: We included 39 studies (35 RCTs, two quasi-RCTs and two cohort studies); and 29 RCTs and two quasi-RCTs (n = 4356) in quantitative analyses for the comparisons: traditional NSAIDs versus placebo, cyclo-oxygenase-2 (COX-2) versus placebo, COX-2 versus traditional NSAIDs, NSAIDs versus NSAIDs, naproxen versus other NSAIDs, low versus high dose. Most trials were at unclear risk of selection bias (n = 29), although blinding of participants and personnel was adequate in 24 trials. Twenty-five trials had low risk of attrition bias and 29 trials had low risk of reporting bias. Risk of bias in both cohort studies was high for study participation, and low or unclear for all other criteria. No trials in the meta-analyses assessed patients with nr-axSpA.Traditional NSAIDs were more beneficial than placebo at six weeks. High quality evidence (four trials, N=850) indicates better pain relief with NSAIDs (pain in control group ranged from 57 to 64 on a 100mm visual analogue scale (VAS) and was 16.5 points lower in the NSAID group (95% confidence interval (CI) -20.8 to -12.2), lower scores indicate less pain, NNT 4 (3 to 6)); moderate quality evidence (one trial, n = 190) indicates improved disease activity with NSAIDs (BASDAI in control group was 54.7 on a 100-point scale and was 17.5 points lower in the NSAID group, 95% CI -23.1 to -11.8), lower scores indicate less disease activity, NNT 3 (2 to 4)); and high quality evidence (two trials, n = 356) indicates improved function with NSAIDs (BASFI in control group was 50.0 on a 100-point scale and was 9.1 points lower in the NSAID group (95% CI -13.0 to -5.1), lower scores indicate better functioning, NNT 5 (3 to 8)). High (five trials, n = 1165) and moderate (three trials, n = 671) quality evidence (downgraded due to potential imprecision) indicates that withdrawals due to AEs and number of serious AEs did not differ significantly between placebo (52/1000 and 2/1000) and NSAID (39/1000 and 3/1000) groups after 12 weeks (risk ratio (RR) 0.75, 95% CI 0.46 to 1.21; and RR 1.69, 95% CI 0.36 to 7.97, respectively). BASMI and radiographic progression were not reported.COX-2 NSAIDS were also more efficacious than placebo at six weeks. High quality evidence (two trials, n = 349) indicates better pain relief with COX-2 (pain in control group was 64 points and was 21.7 points lower in the COX-2 group (95% CI -35.9 to -7.4), NNT 3 (2 to 24)); moderate quality evidence (one trial, n = 193) indicates improved disease activity with COX-2 (BASDAI in control groups was 54.7 points and was 22 points lower in the COX-2 group (95% CI -27.4 to -16.6), NNT 2 (1 to 3)); and high quality evidence (two trials, n = 349) showed improved function with COX-2 (BASFI in control group was 50.0 points and was 13.4 points lower in the COX-2 group (95% CI -17.4 to -9.5), NNT 3 (2 to 4)). Low and moderate quality evidence (three trials, n = 669) (downgraded due to potential imprecision and heterogeneity) indicates that withdrawals due to AEs and number of serious AEs did not differ significantly between placebo (11/1000 and 2/1000) and COX-2 (24/1000 and 2/1000) groups after 12 weeks (RR 2.14, 95% CI 0.36 to 12.56; and RR 0.92, 95% CI 0.14 to 6.21, respectively). BASMI and radiographic progression were not reported.There were no significant differences in benefits (pain on VAS: MD -2.62, 95% CI -10.99 to 5.75; three trials, n = 669) or harms (withdrawals due to AEs: RR 1.04, 95% CI 0.60 to 1.82; four trials, n = 995) between NSAID classes. While indomethacin use resulted in significantly more AEs (RR 1.25, 95% CI 1.06 to 1.48; 11 studies, n = 1135), and neurological AEs (RR 2.34, 95% CI 1.32 to 4.14; nine trials, n = 963) than other NSAIDs, these findings were not robust to sensitivity analyses. We found no important differences in harms between naproxen and other NSAIDs (three trials, n = 646), although other NSAIDs appeared more effective for relieving pain (MD 6.80, 95% CI 3.72 to 9.88; two trials, n = 232). We found no clear dose-response effect on benefits or harms (five studies, n = 1136). Single studies suggest NSAIDs may be effective in retarding radiographic progression, especially in certain subgroups of patients, e.g. patients with high CRP, and that this may be best achieved by continuous rather than on-demand use of NSAIDs. AUTHORS' CONCLUSIONS: High to moderate quality evidence indicates that both traditional and COX-2 NSAIDs are efficacious for treating axSpA, and moderate to low quality evidence indicates harms may not differ from placebo in the short term. Various NSAIDs are equally effective. Continuous NSAID use may reduce radiographic spinal progression, but this requires confirmation.

Self-management education programmes for osteoarthritis.

BACKGROUND: Self-management education programmes are complex interventions specifically targeted at patient education and behaviour modification. They are designed to encourage people with chronic disease to take an active self-management role to supplement medical care and improve outcomes. OBJECTIVES: To assess the effectiveness of self-management education programmes for people with osteoarthritis. SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PyscINFO, SCOPUS and the World Health Organization (WHO) International Clinical Trial Registry Platform were searched, without language restriction, on 17 January 2013. We checked references of reviews and included trials to identify additional studies. SELECTION CRITERIA: Randomised controlled trials of self-management education programmes in people with osteoarthritis were included. Studies with participants receiving passive recipients of care and studies comparing one type of programme versus another were excluded. DATA COLLECTION AND ANALYSIS: In addition to standard methods we extracted components of the self-management interventions using the eight domains of the Health Education Impact Questionnaire (heiQ), and contextual and participant characteristics using PROGRESS-Plus and the Health Literacy Questionnaire (HLQ). Outcomes included self-management of osteoarthritis, participant's positive and active engagement in life, pain, global symptom score, self-reported function, quality of life and withdrawals (including dropouts and those lost to follow-up). We assessed the quality of the body of evidence for these outcomes using the GRADE approach. MAIN RESULTS: We included twenty-nine studies (6,753 participants) that compared self-management education programmes to attention control (five studies), usual care (17 studies), information alone (four studies) or another intervention (seven studies). Although heterogeneous, most interventions included elements of skill and technique acquisition (94%), health-directed activity (85%) and self-monitoring and insight (79%); social integration and support were addressed in only 12%. Most studies did not provide enough information to assess all PROGRESS-Plus items. Eight studies included predominantly Caucasian, educated female participants, and only four provided any information on participants' health literacy. All studies were at high risk of performance and detection bias for self-reported outcomes; 20 studies were at high risk of selection bias, 16 were at high risk of attrition bias, two were at high risk of reporting bias and 12 were at risk of other biases. We deemed attention control as the most appropriate and thus the main comparator.Compared with attention control, self-management programmes may not result in significant benefits at 12 months. Low-quality evidence from one study (344 people) indicates that self-management skills were similar in active and control groups: 5.8 points on a 10-point self-efficacy scale in the control group, and the mean difference (MD) between groups was 0.4 points (95% confidence interval (CI) -0.39 to 1.19). Low-quality evidence from four studies (575 people) indicates that self-management programmes may lead to a small but clinically unimportant reduction in pain: the standardised mean difference (SMD) between groups was -0.26 (95% CI -0.44 to -0.09); pain was 6 points on a 0 to 10 visual analogue scale (VAS) in the control group, treatment resulted in a mean reduction of 0.8 points (95% CI -0.14 to -0.3) on a 10-point scale, with number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 5 to 23). Low-quality evidence from one study (251 people) indicates that the mean global osteoarthritis score was 4.2 on a 0 to 10-point symptom scale (lower better) in the control group, and treatment reduced symptoms by a mean of 0.14 points (95% CI -0.54 to 0.26). This result does not exclude the possibility of a clinically important benefit in some people (0.5 point reduction included in 95% CI). Low-quality evidence from three studies (574 people) showed no signficant difference in function between groups (SMD -0.19, 95% CI -0.5 to 0.11); mean function was 1.29 points on a 0 to 3-point scale in the control group, and treatment resulted in a mean improvement of 0.04 points with self-management (95% CI -0.10 to 0.02). Low-quality evidence from one study (165 people) showed no between-group difference in quality of life (MD -0.01, 95% CI -0.03 to 0.01) from a control group mean of 0.57 units on 0 to 1 well-being scale. Moderate-quality evidence from five studies (937 people) shows similar withdrawal rates between self-management (13%) and control groups (12%): RR 1.11 (95% CI 0.78 to 1.57). Positive and active engagement in life was not measured.Compared with usual care, moderate-quality evidence from 11 studies (up to 1,706 participants) indicates that self-management programmes probably provide small benefits up to 21 months, in terms of self-management skills, pain, osteoarthritis symptoms and function, although these are of doubtful clinical importance, and no improvement in positive and active engagement in life or quality of life. Withdrawal rates were similar. Low to moderate quality evidence indicates no important differences in self-management , pain, symptoms, function, quality of life or withdrawal rates between self-management programmes and information alone or other interventions (exercise, physiotherapy, social support or acupuncture). AUTHORS' CONCLUSIONS: Low to moderate quality evidence indicates that self-management education programmes result in no or small benefits in people with osteoarthritis but are unlikely to cause harm.Compared with attention control, these programmes probably do not improve self-management skills, pain, osteoarthritis symptoms, function or quality of life, and have unknown effects on positive and active engagement in life. Compared with usual care, they may slightly improve self-management skills, pain, function and symptoms, although these benefits are of unlikely clinical importance.Further studies investigating the effects of self-management education programmes, as delivered in the trials in this review, are unlikely to change our conclusions substantially, as confounding from biases across studies would have likely favoured self-management. However, trials assessing other models of self-management education programme delivery may be warranted. These should adequately describe the intervention they deliver and consider the expanded PROGRESS-Plus framework and health literacy, to explore issues of health equity for recipients.

Surgical denervation as a treatment strategy for pain in hand osteoarthritis: a systematic literature review.

OBJECTIVE: Surgical denervation has been proposed as a treatment for pain in hand osteoarthritis (OA). This review aimed to summarise the available evidence and to propose a research agenda. METHODS: A systematic literature search was performed up to September 2022. Two investigators independently identified studies that reported on denervation for OA of the proximal interphalangeal, distal interphalangeal, metacarpophalangeal or carpometacarpal joints. Quality of studies was assessed and study characteristics, patient characteristics, details of the surgical technique and outcomes of the surgery were extracted. RESULTS: Of 169 references, 17 articles reporting on 384 denervations in 351 patients were selected. Sixteen case series reported positive outcomes with respect to pain, function and patient satisfaction. One non-randomised clinical trial reported no difference in outcome when comparing denervation of the first carpometacarpal (CMC I) joint to trapeziectomy. Adverse events were frequent, with sensory abnormalities occurring the most, followed by the need for revision surgery. All studies had significant risk of bias. CONCLUSION: Surgical denervation for pain in hand OA shows some promise, but the available evidence does not allow any conclusions of efficacy and higher-quality research is needed. Techniques should be harmonised and more data regarding how denervation compares to current usual care, other denervation methods or placebo in terms of outcomes and adverse events are needed.

Neuropathic-like pain symptoms in inflammatory hand osteoarthritis lower quality of life and may not decrease under prednisolone treatment.

BACKGROUND: Pain is common in hand osteoarthritis (OA) and multiple types may occur. We investigated the prevalence, associated patient characteristics, influence on health-related quality of life (HR-QoL) and response to anti-inflammatory treatment of neuropathic-like pain in inflammatory hand OA. METHODS: Data were analysed from a 6-week, randomized, double-blind, placebo-controlled trial investigating prednisolone treatment in 92 patients with painful inflammatory hand OA. Neuropathic-like pain was measured with the painDETECT questionnaire. Associations between baseline characteristics and baseline neuropathic-like pain were analysed with ordinal logistic regression, association of baseline neuropathic-like pain symptoms with baseline HR-QoL with linear regression, painDETECT and visual analogue scale (VAS) change from baseline to week 6 and interaction of painDETECT with prednisolone efficacy on VAS pain change from baseline to week 6 with generalized estimating equations (GEE). RESULTS: Of 91 patients (79% female, mean age 64) with complete painDETECT data at baseline, 53% were unlikely to have neuropathic-like pain, 31% were indeterminate and 16% were likely to have neuropathic-like pain. Neuropathic-like pain was associated with female sex, less radiographic damage and more comorbidities. Patients with neuropathic-like pain had lower HR-QoL (PCS-6.5 [95% CI -10.4 to -2.6]) than those without. Neuropathic-like pain symptoms remained under prednisolone treatment and no interaction was seen between painDETECT and prednisolone efficacy on VAS pain. CONCLUSIONS: In this study, 16% of inflammatory hand OA patients had neuropathic-like pain. They were more often female, had more comorbidities and had lower QoL than those without. Neuropathic-like pain symptoms remained despite prednisolone treatment and did not seem to affect the outcome of prednisolone treatment. SIGNIFICANCE: Pain is the dominant symptom in hand OA, with an unclear aetiology. In this study, we found that neuropathic-like pain may play a role in hand OA, that it showed associations with female sex, younger age and more comorbidities and that it lowered health-related quality of life in hand OA. Neuropathic-like pain in hand OA seems resistant to prednisolone therapy but did not seem to interfere with the treatment of inflammatory pain with prednisolone.

Two-Year Changes in Magnetic Resonance Imaging Features and Pain in Thumb Base Osteoarthritis.

OBJECTIVE: To investigate the two-year course of pain and osteoarthritic features on magnetic resonance imaging (MRI) in the thumb base. METHODS: Patients in the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort who had received radiographic examination, MRI, and clinical examination of the right thumb base at baseline and who had a 2-year follow-up period were studied. Pain on palpation of the thumb base was assessed on a 0-3 scale. MRIs were analyzed with the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis MRI scoring system for synovitis, bone marrow lesions (BMLs), subchondral bone defects, cartilage space loss, osteophytes, and subluxation. Radiographs were assessed for osteophytes and joint space narrowing. We studied the associations of changes in synovitis and BMLs with changes in pain using a logistic regression model adjusted for radiographic damage, with values expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Of 165 patients, 83% were women and the mean age was 60.7 years. At baseline, 65 patients had thumb base pain. At 2-year follow-up, pain had decreased in 32 patients and increased in 33 patients. MRI features remained stable in most patients. Structural MRI features generally deteriorated, while synovitis and BMLs improved in some individuals and deteriorated in others. Change in radiographic osteophytes rarely occurred (n = 10). Increased synovitis (odds ratio [OR] 3.4 [95% CI 1.3-9.3]) and increased BMLs (OR 5.1 [95% CI 2.1-12.6]) were associated with increased pain. Decreased BMLs appeared to be associated with decreased pain (OR 2.7 [95% CI 0.8-8.9]), and reductions in synovitis occurred too infrequently to calculate associations. CONCLUSION: Over 2 years, thumb base pain fluctuated, while MRI features changed in a minority of patients with hand osteoarthritis. Changes in synovitis and BMLs were associated with changes in pain on palpation, even after adjustment for radiographic damage.

The lipid profile for the prediction of prednisolone treatment response in patients with inflammatory hand osteoarthritis: The HOPE study.

Objective: To explore the use of lipidomics for prediction of prednisolone treatment response in patients with inflammatory hand osteoarthritis. Design: The Hand Osteoarthritis Prednisolone Efficacy (HOPE) study included patients (n â€‹= â€‹92) with symptomatic inflammatory hand osteoarthritis, fulfilling the ACR criteria. The present analyses comprised only patients randomized to prednisolone treatment (10 â€‹mg daily, n â€‹= â€‹40). Response to prednisolone treatment was defined according to the OARSI-OMERACT responder criteria at six weeks. Baseline blood samples were obtained non-fasted. Lipid species were quantified in erythrocytes with the Lipidyzer™ platform (Sciex). Oxylipins were analyzed in plasma using an in-house LC-MS/MS platform. Elastic net regularized regression was used to predict prednisolone treatment response based on common patient characteristics alone and including the patients' lipid profile. ROC analyses with 1000 bootstrapped area under the curve (AUC) was used to determine the discriminatory accuracy of the models. Results: Among included patients, 78% fulfilled the OARSI-OMERACT responder criteria. From the general patient characteristics, elastic net selected baseline hand function as only predictor of treatment response, with an AUC of 0.78 (0.56; 0.97). Addition of lipidomics resulted in an AUC of 0.92 (0.78; 0.99) and 0.85 (0.65; 0.98) for inclusion of the Lipidyzer™ platform and oxylipin platform, respectively. Conclusion: Our results suggest that the patients' lipid profile may improve the discriminative accuracy of the prediction of prednisolone treatment response in patients with inflammatory hand osteoarthritis compared to prediction by commonly measured patient characteristics alone. Hence, lipidomics may be a promising field for biomarker discovery for prediction of anti-inflammatory treatment response.

Core outcome measurement instrument selection for physical function in hand osteoarthritis using the OMERACT Filter 2.1 process.

OBJECTIVE: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to measure this domain, as part of the development of a core outcome measurement set. METHODS: Following the OMERACT Filter 2.1 instrument selection process, the (function subscale of) the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA) and Michigan Hand Outcomes Questionnaire (MHQ) were assessed for domain match, feasibility, truth and discrimination. Data gathered from available literature, working group and patient surveys, and additional analyses in two hand osteoarthritis cohorts were used to inform a consensus process. Results were summarized in Summary of Measurements Properties tables and reviewed by the OMERACT technical advisory group. RESULTS: MHQ passed the assessment of domain match and feasibility by the working group and patient research partners. For AUSCAN important limitations in feasibility were noted, but domain match was good. FIHOA did not pass the assessment and was not taken through the follow-up assessment. Based on published literature, reliability and construct/longitudinal validity of both MHQ and AUSCAN fulfilled OMERACT standards. While clinical trial discrimination and thresholds of meaning were good for AUSCAN, results for MHQ were ambiguous. CONCLUSION: MHQ was provisionally endorsed as OMERACT core outcome measure for the core domain physical function. While AUSCAN may have better metric properties than MHQ, it received provisional endorsement as a second measure of function due to important feasibility issues. A research agenda to merit full endorsement was set.