Association of rheumatoid factor, anti-citrullinated protein antibodies and shared epitope with clinical response to initial treatment in patients with early rheumatoid arthritis: data from a randomised controlled trial.

OBJECTIVES: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT). METHODS: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking. RESULTS: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks. CONCLUSIONS: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice. TRIAL REGISTRATION NUMBER: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Non-adherence to urate lowering therapy in gout after 5 years is related to poor outcomes-results from the NOR-Gout study.

OBJECTIVES: Patients with gout need to adhere to medication over time to achieve good outcomes. We assessed self-reported adherence to medication with urate lowering therapy (ULT) 5 years after a treat-to-target intervention and studied how non-adherence was related to baseline demographic and disease variables. METHODS: Patients in the NOR-Gout observational study were included after a recent gout flare and serum urate >360 µmol/L. Patients (mean age 56.2 (S.D. 13.6), 94.5% males, 17.2% with tophi) attended tight-control visits over one year with escalating urate lowering therapy using a treat-to-target strategy. Five-year follow-up included the Medication Adherence Report Scale (MARS-5) questionnaire (range 5-25) for adherence. Flares and SUA target achievement were compared for 5-year adherence to medication. RESULTS: At 5-years most of the 163 patients used ULT (95.1%). MARS-5 adherence scores after 5 years were high (median 24, interquartile range 22-25). Patients in the lowest MARS-5 quartile had, compared to the highest quartile, more often a flare during the last year of follow-up (33.3% vs. 9.5%, P=0.004), and reached the 5-yr serum urate treatment target less frequently (45.2% vs. 87.5%, P<0.001). Baseline lower age (OR 0.56, 95%CI 0.39-0.79), non-European origin (OR 0.22, 95%CI 0.06-0.80), lower SF-36 mental health scores (OR 0.94, 95%CI 0.91-0.98) and less joint pain during last flare (OR 0.73, 95%CI 0.58-0.92) were independent risk factors for non-adherence to medication. CONCLUSIONS: Patients reported after 5 years high adherence to medication. Non-adherence was related to more flares and less urate target achievement. Younger age and non-European origin were associated with non-adherence.

Remission Is the Mission in Gout.

Remission is a concept that rheumatologists have accepted as an explicit goal for treatment of their patients with inflammatory disease. With its Latin origins (remittere, to send back), remission has been used as a noun with different meanings. According to the Oxford English Dictionary, one meaning is a cancellation of a debt, charge, or penalty.

Interstitial Lung Disease in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Initiating Biologics and Controls: Data From 5 Nordic Registries.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most common pulmonary manifestations of rheumatoid arthritis (RA), but its prevalence has not been investigated in psoriatic arthritis (PsA). The role of methotrexate (MTX) in ILD development remains under debate. This study (1) compares the incidences of ILD in patients with RA or PsA initiating a first biologic disease-modifying antirheumatic drug (bDMARD) to that in the general population, and (2) investigates the role of MTX comedication on ILD incidence. METHODS: Patients were identified in 5 rheumatology registries. Demographics, MTX use, and disease activity were retrieved. Matched subjects from the general population were available from 4 countries. Incidence of ILD during follow-up of up to 5 years was assessed through national patient registries. Subjects with prior ILD were excluded. Adjusted hazard ratios (HRs) were calculated for ILD incidence in patients vs the general population, and for MTX users vs nonusers. RESULTS: During follow-up of 29,478 patients with RA and 10,919 patients with PsA initiating a first bDMARD and 362,087 population subjects, 225, 23, and 251 cases of ILD were identified, respectively. HRs for ILD (vs population subjects) were 9.7 (95% CI 7.97-11.91) in RA and 4.4 (95% CI 2.83-6.97) in PsA. HRs for ILD with MTX comedication (vs nonuse) were 1.0 (95% CI 0.72-1.25) in RA and 0.9 (95% CI 0.38-2.05) in PsA. CONCLUSION: Among patients with RA and PsA initiating a bDMARD, the risk of ILD was higher than in the general population, and was highest in RA. MTX comedication was not a risk determinant for ILD.

Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial.

OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. METHODS: This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. RESULTS: Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. CONCLUSION: In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. TRIAL REGISTRATION NUMBERS: EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308.

2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

EULAR recommendations for the non-pharmacological management of systemic lupus erythematosus and systemic sclerosis.

OBJECTIVE: To develop evidence-based recommendations for the non-pharmacological management of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). METHODS: A task force comprising 7 rheumatologists, 15 other healthcare professionals and 3 patients was established. Following a systematic literature review performed to inform the recommendations, statements were formulated, discussed during online meetings and graded based on risk of bias assessment, level of evidence (LoE) and strength of recommendation (SoR; scale A-D, A comprising consistent LoE 1 studies, D comprising LoE 4 or inconsistent studies), following the European Alliance of Associations for Rheumatology standard operating procedure. Level of agreement (LoA; scale 0-10, 0 denoting complete disagreement, 10 denoting complete agreement) was determined for each statement through online voting. RESULTS: Four overarching principles and 12 recommendations were developed. These concerned common and disease-specific aspects of non-pharmacological management. SoR ranged from A to D. The mean LoA with the overarching principles and recommendations ranged from 8.4 to 9.7. Briefly, non-pharmacological management of SLE and SSc should be tailored, person-centred and participatory. It is not intended to preclude but rather complement pharmacotherapy. Patients should be offered education and support for physical exercise, smoking cessation and avoidance of cold exposure. Photoprotection and psychosocial interventions are important for SLE patients, while mouth and hand exercises are important in SSc. CONCLUSIONS: The recommendations will guide healthcare professionals and patients towards a holistic and personalised management of SLE and SSc. Research and educational agendas were developed to address needs towards a higher evidence level, enhancement of clinician-patient communication and improved outcomes.

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.

BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025). RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%. CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments. TRIAL REGISTRATION NUMBER: NCT01491815.

Course and predictors of work productivity in gout - results from the NOR-Gout longitudinal 2-year treat-to-target study.

OBJECTIVES: In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years. METHODS: Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables. RESULTS: At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1. CONCLUSIONS: In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication.

Serious infections in patients with rheumatoid arthritis and psoriatic arthritis treated with tumour necrosis factor inhibitors: data from register linkage of the NOR-DMARD study.

OBJECTIVES: To estimate the incidence of serious infections (SIs) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) treated with tumour necrosis factor inhibitor (TNFi), and compare risk of SIs between patients with RA and PsA. METHODS: We included patients with RA and PsA from the NORwegian-Disease Modifying Anti-Rheumatic Drug registry starting TNFi treatment. Crude incidence rates (IRs) and IR ratio for SIs were calculated. The risk of SIs in patients with RA and PsA was compared using adjusted Cox-regression models. RESULTS: A total of 3169 TNFi treatment courses (RA/PsA: 1778/1391) were identified in 2359 patients. Patients with RA were significantly older with more extensive use of co-medication. The crude IRs for SIs were 4.17 (95% CI 3.52 to 4.95) in patients with RA and 2.16 (95% CI 1.66 to 2.81) in patients with PsA. Compared with the patients with RA, patients with PsA had a lower risk of SIs (HR 0.59, 95% CI 0.41 to 0.85, p=0.004) in complete set analysis. The reduced risk in PsA versus RA remained significant after multiple adjustments and consistent across strata based on age, gender and disease status. CONCLUSIONS: Compared with patients with RA, the risk of SIs was significantly lower in patients with PsA during TNFi exposure.

Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment.

OBJECTIVES: Fatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up. METHODS: Data were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression. RESULTS: 205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months. CONCLUSIONS: Fatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.

Associations between fluorescence optical imaging and magnetic resonance imaging and symptoms in hand osteoarthritis.

OBJECTIVES: To investigate whether Fluorescence Optical Imaging (FOI) enhancement and MRI-defined synovitis are associated with pain and physical function in hand OA patients. METHODS: Bilateral FOI scans and MRI of the dominant hand were available for 221 patients. Finger joints were examined for tenderness on palpation. Pain in individual finger joints during the last 24 h and last 6 weeks and hand pain intensity by the Australian/Canadian hand index and Numeric Rating Scale were self-reported. On joint level, we applied logistic regression with generalized estimating equations to examine whether FOI enhancement and MRI-defined synovitis were associated with pain in the same joint. On subject level, we applied linear regression to assess whether FOI and MRI sum scores were associated with pain intensity and physical function. RESULTS: Metacarpophalangeal and thumb base joints were excluded from analyses due to little/no FOI enhancement. Finger joints with FOI enhancement on the composite image had higher odds (95% CI) of pain during the last 6 weeks [grade 1: 1.4 (1.2-1.6); grade 2-3: 2.1 (1.7-2.6)]. Similar results were found for joint pain during the last 24 h and joint tenderness in fingers. Numerically stronger associations were found between MRI-defined synovitis and finger joint pain/tenderness. FOI and MRI sum scores demonstrated no/weak associations with hand pain and physical function. CONCLUSION: FOI enhancement and MRI-defined synovitis were associated with pain in the same finger joint. None of the imaging modalities demonstrated consistent associations with pain, stiffness and physical function on subject level.

Associations between joint pathologies and central sensitization in persons with hand osteoarthritis: results from the Nor-Hand study.

OBJECTIVE: Pain sensitization is associated with pain severity in persons with hand OA. What contributes to pain sensitization is unclear. This study explores whether hand OA pathologies and symptom duration are related to central sensitization. METHOD: Participants with hand OA in the Nor-Hand study underwent bilateral hand radiography and US examination. Central sensitization was assessed with pressure pain thresholds (PPT) at remote sites (wrist, trapezius and tibialis anterior muscles) and temporal summation. We examined whether hand OA pathologies, independent of each other, including structural severity (Kellgren-Lawrence sum score, presence of erosive hand OA), inflammatory severity (greyscale synovitis and power Doppler activity sum scores) and symptom duration, were related to central sensitization, adjusting for age, sex, BMI, comorbidities and OA-severity of knee/hip. RESULTS: In 291 participants (88% women, median age 61 years, interquartile range 57-66 years) Kellgren-Lawrence, greyscale synovitis and power Doppler activity sum scores were not associated with lower PPTs at remote sites. Persons with erosive hand OA had lower PPTs at the wrist (adjusted beta -0.75, 95% CI -1.32, -0.19) and tibialis anterior (adjusted beta -0.82, 95% CI -1.54, -0.09) and had greater temporal summation (adjusted beta 0.56, 95% CI 0.12, 1.01) compared with persons with non-erosive disease. No associations were found for symptom duration. CONCLUSIONS: A person's overall amount of structural or inflammatory hand OA pathologies was not associated with central sensitization. Although persons with erosive hand OA showed greater signs of central sensitization, the small differences suggest that central sensitization is mainly explained by factors other than joint pathologies.

Two-year reduction of dual-energy CT urate depositions during a treat-to-target strategy in gout in the NOR-Gout longitudinal study.

OBJECTIVES: There is a lack of large longitudinal studies of urate deposition measured by dual-energy CT (DECT) during urate lowering therapy (ULT) in people with gout. We explored longitudinal changes in DECT urate depositions during a treat-to-target strategy with ULT in gout. METHODS: Patients with a recent gout flare and serum-urate (sUA) >360 µmol/l attended tight-control visits during escalating ULT. The treatment target was sUA <360 µmol/l, and <300 µmol/l if presence of tophi. A DECT scanner (General Electric Discovery CT750 HD) acquired data from bilateral forefeet and ankles at baseline and after one and two years. Images were scored in known order, using the semi-quantitative Bayat method, by one experienced radiologist who was blinded to serum urate and clinical data. Four regions were scored: the first metatarsophalangeal (MTP1) joint, the other joints of the toes, the ankles and midfeet, and all tendons in the feet and ankles. RESULTS: DECT was measured at baseline in 187 of 211 patients. The mean (s.d.) serum urate level (µmol/l) decreased from 501 (80) at baseline to 311 (48) at 12 months, and 322 (67) at 24 months. DECT scores at all locations decreased during both the first and the second year (P <0.001 for all comparisons vs baseline), both for patients achieving and not achieving the sUA treatment target. CONCLUSIONS: In patients with gout, urate depositions in ankles and feet as measured by DECT decreased both in the first and the second year, when patients were treated using a treat-to-target ULT strategy.

Blood chemokine levels are markers of disease activity but not predictors of remission in early rheumatoid arthritis.

OBJECTIVES: In early rheumatoid arthritis (eRA) plasma levels of specific chemokines have been shown to correlate with disease activity. However, it is unclear whether pre-treatment chemokine levels can predict disease remission at week 24, and it is not known how biological treatments with different modes of action affect plasma chemokine levels in patients with untreated eRA. METHODS: This study included 347 Swedish patients with untreated eRA from the larger NORD-STAR randomised treatment trial. Here, eRA patients were treated with methotrexate combined with either prednisolone, anti-TNF (certolizumab-pegol), CTLA-4Ig (abatacept) or anti-IL6 receptor (tocilizumab). The primary clinical outcome was remission by clinical disease activity index (CDAI) defined as CDAI ≤ 2.8. Disease activity was assessed by CDAI, DAS28-ESR, DAS28-CRP, swollen joint counts, tender joint counts, ESR and CRP. The plasma concentrations of 14 chemokines were measured at baseline and after 24 weeks of treatment by bead-based immunoassay or ELISA. RESULTS: Baseline plasma concentrations of CXCL10, CXCL8, CXCL9, CXCL11, CXCL5 and CCL2 correlated with baseline disease activity measures. After 24 weeks of treatment, plasma levels of CXCL10, CXCL8, CXCL9, CXCL11 and CXCL13 decreased in all treatment groups except in patients treated with anti-IL6 receptor. In multivariate factor analysis, plasma chemokine levels at baseline could not differentiate patients who attained remission by week 24 from those who did not in any of the treatment groups. CONCLUSIONS: In patients with untreated eRA, plasma levels of several chemokines correlate with disease activity at baseline but cannot predict remission after 24 weeks of treatment with methotrexate combined with prednisolone, anti­TNF, CTLA­4Ig or anti­IL6R.

Sarcoidosis with musculoskeletal manifestations: systematic review of non-pharmacological and pharmacological treatments.

We aimed to summarise effects and use of non-pharmacological and pharmacological treatments for sarcoidosis with musculoskeletal manifestations. We systematically searched the Cochrane Library, Ovid MEDLINE, Embase, CINAHL, AMED, Scopus, clinical.trials.gov, PROSPERO and PEDro for systematic reviews from 2014 to 2022 and for primary studies from date of inception to March 29, 2022, and studies with patients diagnosed with sarcoidosis with musculoskeletal manifestations. Inclusion criteria required that studies reported effects of non-pharmacological and/or pharmacological treatments or number of patients receiving these treatments. Results were reported narratively and in forest plots. Eleven studies were included. No systematic reviews fulfilled our inclusion criteria. None of the included studies had a control group. We found that between 23 and 100% received corticosteroids, 0-100% received NSAIDs, 5-100% received hydroxychloroquine, 12-100% received methotrexate, 0-100% received TNF inhibitors, and 3-4% received azathioprine. Only ten patients in one study had used non-pharmacological treatments, including occupational therapy, chiropractic and acupuncture. There are no controlled studies on treatment effects for patients with sarcoidosis with musculoskeletal manifestations. We found 11 studies reporting use of pharmacological treatments and only one study reporting use of non-pharmacological treatments. Our study identified major research gaps for pharmacological and non-pharmacological treatment in musculoskeletal sarcoidosis and warrant randomised clinical trials for both.

Which factors predict discordance between a patient and physician on a gout flare?

OBJECTIVE: To investigate the factors associated with discordance between patient and physician on the presence of a gout flare. METHODS: Patients' self-reports of current gout flares were assessed with the question, 'Are you having a gout flare today?' which was then compared with a concurrent, blinded, physician's assessment. Based on agreement or disagreement with physicians on the presence of a gout flare, flares were divided into concordant and discordant groups, respectively. Within the discordant group, two subgroups-patient-reported flare but the physician disagreed and physician-reported flare but the patient disagreed-were identified. The factors associated with discordance were analysed with multivariable logistic regression analysis. RESULTS: Of 268 gout flares, 81 (30.2%) flares were discordant, with either patient or physician disagreeing on the presence of a flare. Of the discordant flares, in 57 (70.4%) the patient reported a flare but the physician disagreed. In multivariable logistic regression analysis adjusted for demographics, disagreement among patients and physicians on the presence of a gout flare was associated with lower pain scores at rest [odds ratio (OR) for each point increase on 0-10 point pain scale 0.81 (95% Wald CI 0.73, 0.90), P < 0.0001] and less presence of joint swelling [OR 0.24 (95% CI 0.10, 0.61), P = 0.003] or joint warmth [OR 0.39 (95% CI 0.20, 0.75), P = 0.005]. CONCLUSION: Although patients and physicians generally agree about the presence of gout flare, discordance may occur in the setting of low pain scores and in the absence of swollen or warm joints.

Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial.

Importance: Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear. Objective: To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission. Design, Setting, and Participants: ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019. Interventions: Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80). Main Outcomes and Measures: The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin. Results: Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred. Conclusions and Relevance: Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01881308.

Ultrasound shows rapid reduction of crystal depositions during a treat-to-target approach in gout patients: 12-month results from the NOR-Gout study.

OBJECTIVES: As ultrasound is sensitive for detecting crystal depositions in patients with gout, our objectives were to explore the main locations for depositions and the extent of dissolution of depositions during a treat-to-target approach with urate lowering treatment (ULT) in patients with gout. METHODS: Patients with a recent flare of gout were consecutively included in this single-centre study and managed by a treat-to-target approach with ULT. All patients were assessed at baseline, 3, 6 and 12 months including bilateral ultrasound examinations of joints/tendons/entheses of hands, elbows, knees, ankles and feet. A new semiquantitative scoring system of 0-3 of elementary lesions (double contour (DC), tophi and aggregates) was applied to quantify the amount of depositions during the follow-up. RESULTS: 209 of the patients were evaluated with ultrasound at baseline (mean (SD) age 56.4 (13.8) years and disease duration 7.9 (7.7) years, 95.2% men). The serum urate levels decreased from baseline to 12 months (mean (SD) 500 (77) to 312 (49) µmol/L) (p<0.001)). The first metatarsophalangeal joint was the most frequent location for all the elementary lesions and erosions were associated with higher levels of crystal depositions. From baseline to 12 months, mean sum scores decreased for DC (4.3 to 1.3), tophi (6.5 to 3.8) and aggregates (9.3 to 6.7) (p<0.001 for all), with DC being most sensitive to change. CONCLUSIONS: The ultrasound scoring system for crystal depositions was sensitive to change and showed that a treat-to-target approach with ULT resulted in significant reductions of all the depositions, most extensively for DC.

2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout.

Although gout is the most common inflammatory arthritis, it is still frequently misdiagnosed. New data on imaging and clinical diagnosis have become available since the first EULAR recommendations for the diagnosis of gout in 2006. This prompted a systematic review and update of the 2006 recommendations. A systematic review of the literature concerning all aspects of gout diagnosis was performed. Recommendations were formulated using a Delphi consensus approach. Eight key recommendations were generated. A search for crystals in synovial fluid or tophus aspirates is recommended in every person with suspected gout, because demonstration of monosodium urate (MSU) crystals allows a definite diagnosis of gout. There was consensus that a number of suggestive clinical features support a clinical diagnosis of gout. These are monoarticular involvement of a foot or ankle joint (especially the first metatarsophalangeal joint); previous episodes of similar acute arthritis; rapid onset of severe pain and swelling; erythema; male gender and associated cardiovascular diseases and hyperuricaemia. When crystal identification is not possible, it is recommended that any atypical presentation should be investigated by imaging, in particular with ultrasound to seek features suggestive of MSU crystal deposition (double contour sign and tophi). There was consensus that a diagnosis of gout should not be based on the presence of hyperuricaemia alone. There was also a strong recommendation that all people with gout should be systematically assessed for presence of associated comorbidities and risk factors for cardiovascular disease, as well as for risk factors for chronic hyperuricaemia. Eight updated, evidence-based, expert consensus recommendations for the diagnosis of gout are proposed.