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.

Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient's response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy. METHODS: This study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography-mass spectrometry (LC-MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes. RESULTS: Patients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24. CONCLUSIONS: Treatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.

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.

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.

Changes in Tophus Composition During Urate-Lowering Therapy: A Dual-Energy Computed Tomography Study.

OBJECTIVE: The gouty tophus is an organized structure composed of monosodium urate (MSU) crystals and chronic inflammatory soft tissue. This dual-energy computed tomography (DECT) study aimed to determine whether the composition of the tophus changes during urate-lowering therapy. METHODS: Serial DECT scans from 32 people with gout were obtained over 2 years of allopurinol therapy, dose-escalated to serum urate of <0.36 mmoles/liter. Up to 5 index tophi were selected for each patient, with 103 separate tophi included in the analysis. Using manual outlining methods of conventional CT and DECT scans, the same index tophi were serially measured for total tophus volume and urate volume. For each tophus, the soft tissue volume was then calculated by subtracting the urate volume from the total tophus volume. RESULTS: The mean ± SD serum urate reduced from 0.43 ± 0.03 mmoles/liter at baseline to 0.31 ± 0.02 mmoles/liter at year 2. The mean ± SD total tophus volume reduced over the 2-year period from 5.17 ± 5.55 cm3 to 2.61 ± 2.73 cm3 (P < 0.0001). Greater reductions in tophus urate volumes than tophus soft tissue volumes were observed; the tophus urate volume decreased by 70.6%, and tophus soft tissue volume decreased by 37.8% (P < 0.0001). The mean tophus urate:soft tissue ratio reduced from 0.15 at baseline to 0.05 at year 2 (P < 0.001). CONCLUSION: The composition of the tophus is dynamic and changes during urate-lowering therapy for gout management. The soft tissue component of the tophus is slower to respond and may persist without measurable MSU crystal deposition.

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.

One- and 2-year flare rates after treat-to-target and tight-control therapy of gout: results from the NOR-Gout study.

OBJECTIVES: To explore the frequency and predictors of flares over 2 years during a treat-to-target strategy with urate-lowering therapy (ULT) in patients with gout. METHODS: In the treat-to-target, tight control NOR-Gout study patients started ULT with escalating doses of allopurinol. Flares were recorded over 2 years. Baseline predictors of flares during months 9-12 in year 1 and during year 2 were analyzed by multivariable logistic regression. RESULTS: Of 211 patients included (mean age 56.4 years, disease duration 7.8 years, 95% males), 81% (150/186) of patients experienced at least one gout flare during the first year and 26% (45/173) during the second year. The highest frequency of flares in the first year was seen during months 3-6 (46.8% of patients). Baseline crystal depositions detected by ultrasound and by dual-energy computed tomography (DECT) were the only variables which predicted flares both during the first period of interest at months 9-12 (OR 1.033; 95% CI 1.010-1.057, and OR 1.056; 95% CI 1.007-1.108) and also in year 2. Baseline subcutaneous tophi (OR 2.42, 95% CI 1.50-5.59) and prior use of colchicine at baseline (OR 2.48, 95% CI 1.28-4.79) were independent predictors of flares during months 9-12, whereas self-efficacy for pain was a protective predictor (OR 0.98 per unit, 95% CI 0.964-0.996). CONCLUSIONS: In patients with gout, flares remain frequent during the first year of a treat-to-target ULT strategy, especially during months 3-6, but are much less frequent during year 2. Baseline crystal depositions predict flares over 2 years, supporting ULT early during disease course. TRIAL REGISTRATION: ACTRN12618001372279.

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.

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.

Predicting achievement of the treatment targets at 6 months from 3-month response levels in rheumatoid arthritis: data from real-life follow-up in the NOR-DMARD study.

OBJECTIVE: When initiating a new therapy in patients with rheumatoid arthritis (RA), current treatment recommendations suggest escalating therapy in case of poor clinical improvement by 3 months or if the treatment target has not been reached by 6 months. We investigated which disease activity improvement levels at 3 months predicted achievement of the treatment targets at 6 months in a real-life clinical setting. METHODS: We included 1610 patients with RA enrolled in the NOR-DMARD study between 2000 and 2012. Analyses were performed for the total group of patients and repeated for subgroups stratified by baseline disease activity, disease duration or treatment with methotrexate or a tumour necrosis factor inhibitor. We used a diagnostic test approach to explore the associations between 3-month response and 6-month outcome. RESULTS: Not achieving 50% improvement in Simplified Disease Activity Index (SDAI) by 3 months significantly decreased the likelihood of reaching remission at 6 months in all subgroups (negative likelihood ratios (LRs-) 0.15-0.36). Patients with high disease activity when initiating treatment were likely to fail reaching remission if they achieved less than SDAI 70% response by 3 months (LR- 0.25 and negative predictive value 0.98). Achieving a major response (SDAI 85%) at 3 months significantly increased the likelihood of reaching remission at 6 months (LRs+ 6.56). CONCLUSION: Levels of 3-month disease activity improvement can inform clinicians when deciding to continue or adjust ongoing therapy in a treat-to-target strategy aiming for remission or low disease activity within 6 months. The required levels of 3-month improvement varied with baseline disease activity.

Health-related quality of life in patients with psoriatic and rheumatoid arthritis: data from the prospective multicentre NOR-DMARD study compared with Norwegian general population controls.

OBJECTIVES: To compare (1) Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), scale scores and Short Form-6 dimensions (SF-6D) between patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) and Norwegian general population controls and (2) improvements in these measures between patients with RA and PsA. METHODS: Analyses of covariance were performed to compare SF-36 measures between first-time enrolled patients with RA (n=3898) and PsA (n=1515) from the prospective observational multicentre NORwegian-Disease Modifying Anti-Rheumatic Drug study (6 months follow-up) and general population controls (n=2323). RESULTS: In age and gender-adjusted analyses, patients with PsA compared with patients with RA had similar PCS, MCS and SF-6D (p≥0.14), worse vitality and general health, but better physical functioning at 0/6 months (p≤0.03). With additional 28-joint disease activity scores adjustment as a proxy for joint inflammation, PCS, most scale scores and SF-6D were worse in patients with PsA than patients with RA at 0/3/6 months (p≤0.01). PCS was more impaired than MCS both in RA and PsA compared with general population controls (p≤0.001). Mean 3-month and 6-month improvements after disease-modifying anti-rheumatic drug treatment were larger in patients with RA than patients with PsA for bodily pain, vitality and mental health (p≤0.02). CONCLUSIONS: Health-related quality of life was overall similar in patients with RA and patients with PsA-with a tendency to worse scores in PsA-and worse compared with Norwegian general population controls.

Study for Updated Gout Classification Criteria: Identification of Features to Classify Gout.

OBJECTIVE: To determine which clinical, laboratory, and imaging features most accurately distinguished gout from non-gout. METHODS: We performed a cross-sectional study of consecutive rheumatology clinic patients with ≥1 swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (two-thirds) and test sample (one-third). Univariate and multivariate association between clinical features and monosodium urate-defined gout was determined using logistic regression modeling. Shrinkage of regression weights was performed to prevent overfitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement. RESULTS: In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n = 653), the following features were selected for the final model: joint erythema (multivariate odds ratio [OR] 2.13), difficulty walking (multivariate OR 7.34), time to maximal pain <24 hours (multivariate OR 1.32), resolution by 2 weeks (multivariate OR 3.58), tophus (multivariate OR 7.29), first metatarsophalangeal (MTP1) joint ever involved (multivariate OR 2.30), location of currently tender joints in other foot/ankle (multivariate OR 2.28) or MTP1 joint (multivariate OR 2.82), serum urate level >6 mg/dl (0.36 mmoles/liter; multivariate OR 3.35), ultrasound double contour sign (multivariate OR 7.23), and radiograph erosion or cyst (multivariate OR 2.49). The final model performed adequately in the test set, with no evidence of misfit, high discrimination, and predictive ability. MTP1 joint involvement was the most common joint pattern (39.4%) in gout cases. CONCLUSION: Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria.

Cost-effectiveness of TNF inhibitors vs synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a Markov model study based on two longitudinal observational studies.

OBJECTIVE: The objective of this study was to estimate the additional costs and health benefits of adding a TNF inhibitor (TNFi) (adalimumab, certolizumab, etanercept, golimumab, infliximab) to a synthetic DMARD (sDMARD), e.g. MTX, in patients with RA. METHODS: We developed the Norwegian RA model as a Markov model simulating 10 years of treatment with either TNFi plus sDMARDs (TNFi strategy) or sDMARDs alone (synthetic strategy). Patients in both strategies started in one of seven health states, based on the Short Form-6 Dimensions (SF-6D). The patients could move to better or worse health states according to transition probabilities. In the TNFi strategy, patients could stay on TNFi (including switch of TNFi), or switch to non-TNFi-biologics (abatacept, rituximab, tocilizumab), sDMARDs or no DMARD. In the synthetic strategy, patients remained on sDMARDs. Data from two observational studies were used for the assessment of resource use and utilities in the health states. Health benefits were evaluated using the EuroQol-5 Dimensions (EQ-5D) and SF-6D. RESULTS: The Norwegian RA model predicted that 10-year discounted health care costs totalled €124,942 (€475,266 including production losses) for the TNFi strategy and €65,584 (€436,517) for the synthetic strategy. The cost per additionally gained quality-adjusted life-year of adding a TNFi was €92,557 (€60,227 including production losses) using SF-6D and €61,285 (€39,841) using EQ-5D. Including health care costs only, the probability that TNFi treatment was cost-effective was 90% when using EQ-5D, assuming a Norwegian willingness-to-pay level of €67,300. CONCLUSION: TNFi treatment for RA is cost-effective when accounting for production losses. Excluding production losses, TNFi treatment is cost-effective using EQ-5D, but not SF-6D.

Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000-2010.

OBJECTIVES: To investigate whether baseline disease activity levels and responses in patients with rheumatoid arthritis (RA) changed during the period 2000-2010. METHODS: Data were provided by the Norwegian disease-modifying antirheumatic drug (NOR-DMARD) study. Patients with inflammatory joint diseases starting new treatment with disease-modifying antirheumatic drugs (DMARDs) were consecutively included and followed longitudinally. Time trend analyses were performed in methotrexate (MTX)-naïve RA patients starting MTX monotherapy (MTX mono) and biologic DMARD (bDMARD)-naïve RA patients starting tumour necrosis factor inhibitors+MTX (TNFi+MTX). RESULTS: A total of 2573 patients were included in the analyses: MTX mono n=1866 (69.9% female, 62.0% RF+, mean (SD) age 56.0 (13.7) years, median (25-75 percentile) time from diagnosis 0.2 (0.01-2.8) years); TNFi+MTX n=707 (70.3% female, 75.0% RF+, mean (SD) age 52.1 (13.2) years, median (25-75 percentile) time from diagnosis 5.7 (2.0-13.7) years). Significant time trends towards lower baseline disease activity score 28 (DAS28) as well as other disease activity measures were found in both groups (DAS28 from 5.17 to 4.75 in MTX mono and from 5.88 to 4.64 in TNFi+MTX), and disease duration became shorter. Six-month DAS28 remission rates increased significantly over the years (from 17.8 to 37.6 in MTX mono and from 16.9 to 46.3 in TNFi+MTX). CONCLUSIONS: During the last decade, baseline RA disease activity level at the time of starting MTX as well as TNFi+MTX decreased from high to moderate. A more than twofold increase in 6-month remission rates was observed in both groups. Our findings indicate that clinicians have implemented modern, more aggressive treatment strategies, which hopefully will lead to better long-term disease outcomes.

Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monotherapy has failed: data from the NOR-DMARD register.

OBJECTIVES: To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed. METHODS: Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified. RESULTS: Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was -1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX. CONCLUSIONS: Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.

[Osteoarthritis]. / Artrose.

BACKGROUND: Osteoarthritis is among the most common causes of functional disability and severe pain, and the prevalence of arthritic symptoms among adults is more than 50%. The article discusses epidemiology, pathology and treatment options. MATERIAL AND METHODS: The review is based on a non-systematic search in PubMed and the authors' experience with treating this patient group. RESULTS: Osteoarthritis is a degenerative disease which leads to loss of joint functioning. Symptoms usually present in the hip, hands and knees. Women are affected more often than men and the prevalence increases with increasing age. Some families have an increased prevalence of osteoarthritis, but the genetic etiology is not clear. Mechanic conditions such as overweight and heavy physical work explain some of the pathogenesis, but non-mechanical factors are probably involved as well. Loss of weight is likely to have a preventive effect, and surgical correction of mechanic conditions such as hip dysplasia and varus deformity can prevent development of osteoarthritis. Treatment of symptomatic osteoarthritis includes educating the patient and continues with stretching, physical exercise, weight reduction, technical aids (supporting braces, walking sticks) and analgesics. Subsequent options are treatment with paracetamol, NSAIDs and possibly opiates and finally insertion of an artificial joint. Many patients with disabling osteoarthritis function much better and have markedly less pain with an artificial joint. INTERPRETATION: Current treatment options alleviate but do not cure arthritic symptoms; preventive actions should be instigated when possible. Treatment of osteoarthritis involves many medical specialties and treatment modalities.

Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis.

OBJECTIVE: To examine the effectiveness and 2-year retention rates of methotrexate (MTX) in MTX naïve patients with psoriatic arthritis (PsA). METHODS: Data on 430 patients with PsA participating in an ongoing longitudinal observational multicentre study in Norway were analysed. 1218 MTX naïve patients with rheumatoid arthritis (RA) from the same study served as a reference population. Assessments included measures of disease activity (28 joint counts, acute phase reactants), health status and utility scores. Six-month effectiveness data were compared both by crude analyses and with adjustments for age, sex and the respective baseline values. Two-year drug survival was compared by Kaplan-Meier and Cox regression analyses. RESULTS: After 6 months of MTX treatment, both patients with PsA and those with RA improved in most disease activity measures and patient reported outcomes. In the adjusted analysis, patients with PsA tended to have less improvement, but changes were in the same range as in patients with RA. Two-year retention rates of MTX therapy in patients with PsA and RA were 65% and 66%, respectively, with only minor differences in reported reasons for discontinuation. Lower age, longer disease duration and higher Modified Health Assessment Questionnaire (MHAQ) score and patient global assessment were independent predictors of MTX termination within the first 2 years of treatment. CONCLUSION: In this real-life study, MTX treatment was associated with improvement in disease activity and health-related quality of life in patients with PsA after 6 months of treatment. Retention rates of MTX were similar in PsA and RA.

Epidemiological aspects of rheumatoid arthritis: the sex ratio.

Many rheumatic diseases, including rheumatoid arthritis (RA) are more frequent in females than males. The objective of this article was to examine the female versus male perspective regarding prevalence/incidence, etiological factors, disease severity/outcomes, access to therapy and therapeutic responses. We also present results from some new analyses from the patient registers in Oslo to supplement existing literature in this area. We found that the prevalence of RA is higher in females than males, the incidence is 4-5 times higher below the age of 50, but above 60-70 years the female/male ratio is only about 2. Smoking is a consistent predictor of RA in males, but findings have been more inconsistent in females. We could not confirm that health status is worse in females than males when corrections were made for different disease duration and for the underlying tendency of healthy females to report worse subjective health status than males. Some studies and data presented here indicate that females have less access to health services. We also found that female sex reduces the likelihood of achieving treatment response with methotrexate and anti-tumor necrosis factor (anti-TNF) drugs by 30-50%. More research is needed to fully describe the differences between males and females regarding epidemiological data.