ObjectivesTo provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field.MethodsAn international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items.ResultsThe task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high.ConclusionsThese updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA.

PartiCiPants 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care.interventiOns Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was restarted or escalated. Main OutCOMe MeasuresDifference in proportions of patients with major flare (DAS28-CRP based flare longer than three months) between the two groups at 18 months, compared against a non-inferiority margin of 20%. Secondary outcomes included TNF inhibitor use at study end, functioning, quality of life, radiographic progression, and adverse events.results Dose reduction of adalimumab or etanercept was non-inferior to usual care (proportion of patients with major flare at 18 months, 12% v 10%; difference 2%, 95% confidence interval −12% to 12%). In the dose reduction group, TNF inhibitor use could successfully be stopped in 20% (95% confidence interval 13% to 28%), the injection interval successfully increased in 43% (34% to 53%), but no dose reduction was possible in 37% (28% to 46%). Functional status, quality of life, relevant radiographic progression, and adverse events did not differ between the groups, although short lived flares (73% v 27%) and minimal radiographic progression (32% v 15%) were more frequent in dose reduction than usual care. COnClusiOnsA disease activity guided, dose reduction strategy of adalimumab or etanercept to treat rheumatoid arthritis is non-inferior to usual care with regard to major flaring, while resulting in the successful dose reduction or stopping in two thirds of patients.trial registratiOn Dutch trial register (www.trialregister.nl), NTR 3216.

Objective. To evaluate drug survival, effectiveness, pharmacokinetics, immunogenicity, and safety in daily practice after transitioning treatment from original reference infliximab (Remicade [REM]) to a biosimilar infliximab (CT-P13 [Remsima; Inflectra]) in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.Methods. Of the initial 222 REM-treated patients, 192 agreed to transition to CT-P13 and were included in this multicenter prospective cohort study. Changes in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and changes in the CRP levels, infliximab trough levels, and anti-infliximab antibody levels were assessed after 6 months, and adverse events (AEs) were documented. Drug survival and prognostic factors were analyzed using Kaplan-Meier and Cox regression analyses.Results. During 6 months follow-up, 24% of the patients (n = 47) discontinued CT-P13. Thirty-seven patients restarted REM, 7 switched to another biologic drug, and 3 continued without a biologic drug. The DAS28-CRP remained stable from baseline to month 6, with a mean AE SD score of 2.2 AE 0.9 at baseline to 2.2 AE 0.8 at 6 months (difference of 0.0 [95% confidence interval (95% CI) -0.1, 0.2]). The BASDAI increased from a mean AE SD of 3.8 AE 2.0 at baseline to 4.3 AE 2.1 at 6 months (difference of +0.5 [95% CI 0.1, 0.9]). The CRP levels, infliximab trough levels, and anti-infliximab antibody levels did not change. Just prior to CT-P13 discontinuation, the DAS28-CRP components tender joint count and patient's global assessment of disease activity, as well as the BASDAI were increased compared to baseline. The most frequently reported AEs were arthralgia, fatigue, pruritus, and myalgia. A shorter REM infusion interval (hazard ratio: 0.77 [95% CI 0.62, 0.95]) at baseline was predictive of discontinuing CT-P13.Conclusion. In our cohort, one-fourth of patients discontinued CT-P13 during 6 months of follow-up, mainly due to an increase in the subjective features of the tender joint count and the patient's global assessment of disease activity and/or subjective AEs, possibly explained by nocebo effects and/or incorrect causal attribution effects.

Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.

Background The WOMAC is the most widely used self-report measure to evaluate physical functioning in hip or knee osteoarthritis, however its ability to discriminate pain and physical functioning (i.e. discriminate validity) has repeatedly been questioned. Little to no data is available on the discriminant validity of alternative questionnaires that measure the same construct, for instance the Hip and Knee Osteoarthritis Outcome Score (HOOS and KOOS, respectively) and the Lower Extremity Function Scale (LEFS). Therefore, we translated the LEFS to Dutch and studied its psychometric properties (i.e. validity, reliability and responsiveness). In addition, we assessed the discriminate validity of the LEFS, HOOS and KOOS. Methods After translation with a forward/backward protocol, 401 individuals with hip or knee osteoarthritis completed the LEFS, HOOS/KOOS, SF-36, Hospital Anxiety and Depression Scale and Checklist Individual Strength questionnaires. To assess reliability and responsiveness, a sample of 106 and 108 patients completed a comparable set of questionnaires within 3 weeks and 3 months, respectively. Feasibility, validity, reliability and responsiveness were evaluated. Discriminant validity of the LEFS, HOOS and KOOS was examined by contrasting the scales’ correlations with the physical functioning subscale of the SF-36 with the scales’ correlations with the bodily pain subscale of the SF-36. Results The Dutch version of the LEFS was feasible, had good internal consistency (0.96), good reliability (ICC = 0.86), good construct and discriminant validity, and showed no floor or ceiling effects. The minimal detectable change (MDC 90 ) was ten points. Area under the receiver operating characteristic curve (AUC) analyses revealed good (AUC = 0.76) and fair (AUC = 0.63) responsiveness for the LEFS in improved and worsened patients, respectively. Discriminant validity for pain was apparent for the LEFS ( p < 0.01), but not for the HOOS and KOOS ( p = 0.21 and p = 0.20, respectively). Conclusions Considering the LEFS’ good psychometric qualities and ability to discriminate between pain and functioning, we recommend the LEFS as the outcome measure of choice to assess self-reported physical functioning in individuals with hip or knee osteoarthritis.

IMPORTANCE Biologics revolutionized the treatment of psoriasis. Biologics are given in a fixed dose, but lower doses might be possible. OBJECTIVE To investigate whether dose reduction (DR) of biologics in patients with stable psoriasis is noninferior to usual care (UC). DESIGN, SETTING, AND PARTICIPANTS This pragmatic, open-label, prospective, controlled, noninferiority randomized clinical trial was conducted from March 1, 2016, to July 22, 2018, at 6 dermatology departments in the Netherlands. A total of 120 patients with plaque psoriasis and stable low disease activity who were receiving treatment with adalimumab, etanercept, or ustekinumab were studied. INTERVENTIONS Patients were randomized 1:1 to DR (n = 60) or UC (n = 60). In the DR group, injection intervals were prolonged stepwise, leading to 67% and 50% of the original dose. MAIN OUTCOMES AND MEASURES The primary outcome was between-group difference in disease activity corrected for baseline at 12 months compared with the predefined noninferiority margin of 0.5. Secondary outcomes were Psoriasis Area and Severity Index (PASI) score and health-related quality of life (including Dermatology Life Quality Index [DLQI] and Medical Outcomes Study 36-Item Short Form Health Survey scores), proportion of patients with short and persistent flares (defined as PASI and/or DLQI scores >5 for Ն3 months), and proportion of patients with successful dose tapering. RESULTS Of 120 patients (mean [SD] age, 54.0 [13.2] years; 82 [68%] male), 2 patients were lost to follow-up, 2 patients had a protocol violation, and 5 patients had a protocol deviation, leaving 111 patients for the per-protocol analysis (53 in the DR group and 58 in the UC group). The median PASI scores at month 12 were 3.4 (interquartile range [IQR], 2.2-4.5) in the DR group and 2.1 (IQR, 0.6-3.6) in the UC group (mean difference, 1.2; 95% CI, 0.7-1.8). This indicates that noninferiority was not demonstrated for DR compared to UC. The median DLQI score at month 12 was 1.0 (IQR, 0.0-2.0) in the DR group and 0.0 (IQR, 0.0-2.0) in the UC group (mean difference, 0.8; 95% CI, 0.3-1.3), indicating noninferiority for DR compared with UC. No significant difference was found regarding persistent flares between groups (n = 5 in both groups). Twenty-eight patients (53%; 95% CI, 39%-67%) in the DR group tapered their dose successfully at 12 months. No severe adverse events related to the intervention occurred. CONCLUSIONS AND RELEVANCE In this trial, noninferiority was not demonstrated for DR of adalimumab, etanercept, and ustekinumab based on the PASI in patients with psoriasis compared with UC with the chosen noninferiority margin. However, the strategy was noninferior based on the DLQI. Dose tapering did not lead to persistent flares or safety issues.

In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment.