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Objective: There is a need for a widely accepted comprehensive disease activity measure for use in daily practice in patients with psoriatic arthritis (PsA). For this reason, the 3-item Visual Analogue Scale (3VAS) and 4-item Visual Analogue Scale (4VAS) were developed. This study aimed to test construct validity and responsiveness of the 3VAS and 4VAS in a population of patients with newly diagnosed PsA receiving usual care., Methods: Components of the 3VAS (physician global, patient global, patient skin) and 4VAS (physician global, patient pain, patient joint, patient skin) were scored on 0-10 VAS scales. Agreement of low disease activity (LDA) state between 3VAS/4VAS and other composite measures was tested using Venn diagrams. Construct validity and responsiveness (3-month interval) were assessed using Spearman correlation coefficients and standardised response means (SRM) with effect sizes (ES), respectively, following hypothesis generation. Both 3VAS/4VAS were also compared with several patient-reported outcome measures., Results: Data from 629 patients were used. Both 3VAS (ES=0.48, SRM 0.52) and 4VAS (ES=0.48, SRM=0.50) showed responsiveness similar to Disease Activity in PSoriatic Arthritis (DAPSA) and Disease Activity Score-28 (DAS28). Both measures had a strong correlation with DAPSA (r=0.80-0.87), Psoriatic Arthritis Disease Activity Score (PASDAS) (r=0.89) and Routine Assessment of Patient Index Data 3 (RAPID3) (r=0.84-0.92). 3VAS and 4VAS had the highest agreement with PASDAS in categorising patients to LDA at 12 months., Conclusion: This is the first study assessing the performance of the 3VAS and 4VAS in an observational cohort of patients with early PsA. Both measures have promising performance characteristics, showing strong correlations and good discrimination with existing composite measures. The 4VAS may be the preferred version with better face validity., Competing Interests: Competing interests: WT has received research funding, consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, GSK, MSD, Novartis, Ono Pharma, Pfizer and UCB., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Whereas in the treatment of rheumatoid arthritis much evidence exists on the effects of current pharmacologic treatment on clinical outcomes, little is known about the effects on patient-reported outcomes. This systematic review aims to evaluate the effects of disease-modifying antirheumatic drugs (DMARDs) on the patient-relevant domains of pain, fatigue, activity limitation, overall emotional and physical health impact, and work/school/housework ability and productivity., Methods: A literature search was conducted to identify randomized controlled trials wherein registered DMARDs were compared with placebo or methotrexate and reported the effects on patient-reported outcomes included in the International Consortium of Health Outcomes Measurement standard set for inflammatory arthritis. Random effects meta-analyses using the standardized mean differences of change scores as the effect measure were performed for the domains of pain, fatigue, and activity limitation, comparing DMARDs with placebo and methotrexate. The other 2 domains were presented narratively., Results: Across the 5 domains, 69 records belonging to 52 studies were identified. All meta-analyses showed a decrease of burden when DMARDs were compared with placebo (standardized mean differences [95% confidence interval] in pain -0.80 [-0.99, -0.61], fatigue -0.48 [-0.64, -0.32], and activity limitation -0.56 [- 0.63, -0.49]) and when compared with methotrexate (-0.55 [-0.70, -0.41), -0.44 [-0.55, -0.33], and - 0.37 [-0.44, -0.30], respectively)., Conclusion: DMARDs decrease the burden in all the domains that are relevant to patients. Effect sizes may be influenced by DMARD type. Therefore, in the decision for rheumatoid arthritis treatment, patient-reported outcomes should be taken into account., (© 2022 American College of Rheumatology.)

Hepatotoxicity is a serious adverse drug reaction related to methotrexate (MTX). However, the cause of drug-induced liver injury (DILI) is still unclear and unpredictable. Genetic risk factors may predispose for MTX-DILI. Therefore, we conducted a nested case-control genome-wide association study to explore genetic risk factors associated with MTX-DILI. Seven international groups contributed blood samples and data of patients with rheumatoid arthritis who used MTX. MTX-DILI was defined as an alanine aminotransferase (ALT) level of at least three times the upper limit of normal (ULN), to increase contrast controls ALT levels did not raise above two times the ULN. Per study site, control subjects and patients with MTX-DILI (ratio 3:1) were matched for age, gender, and duration of MTX use. Patients were genotyped using Illumina GSA MD-24v1-0 and data were imputed using the 1000 Genomes reference panel. Single-nucleotide polymorphisms (SNPs) were analyzed using an additive genetic model, corrected for sex, country, and age. A P-value of ≤ 5 × 10 -8 was considered significant, whereas a  P-value of ≤ 5 × 10 -6 was considered suggestive. A total of 108 MTX-DILI cases and 311 controls were included for association analysis. None of the SNPs were significantly associated with MTX-DILI. However, we found seven suggestive genetic variants associated with MTX-DILI (P-values 7.43 × 10 -8 to 4.86 × 10 -6 ). Of those, five SNPs were in the intronic protein-coding regions of FTCDNL1, BCOR, FGF14, RBMS3, and PFDN4/DOK5. Investigation of candidates SPATA9 (rs72783407), PLCG2 (rs60427389), RAVER2 (rs72675408), JAK1 (rs72675451), PTPN2 (rs2476601), MTHFR C677T (rs1801133), and into the HLA region did not show significant findings. No genetic variants associated with MTX-DILI were found, whereas suggestive SNPs need further investigation., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: Achieving low disease activity (LDA) is important in patients with psoriatic arthritis. It is of value to know if health-related quality of life (HRQoL) of patients who reached musculoskeletal low disease activity can be further improved by additionally achieving remission of their psoriasis. So, the aim of this study was to assess HRQoL in patients with active psoriasis who reached disease activity in psoriatic arthritis (DAPSA) LDA after one year of follow-up., Methods: Data were collected from the Dutch south west Psoriatic Arthritis cohort. Musculoskeletal disease activity was measured using DAPSA. Patients who reached DAPSA-LDA after one year were divided based on reaching psoriasis remission (Psoriasis Area and Severity Index [PASI] <1). HRQoL and work productivity were compared between both groups., Results: After one year, 230 (44%) patients with active psoriasis at baseline reached DAPSA-LDA, of which 108 (47%) patients achieved psoriasis remission. The group of patients with active psoriasis (n=122, 53%) contained more men (p=0.023) and scored lower on the 12-item Psoriatic Arthritis Impact of Disease questionnaire (p=0.012). On the Skindex-17 psychosocial subscale, 31% experienced moderate to high impairment and on the symptoms subscale 28% experienced a lot of symptoms. Work productivity did not differ between both groups., Conclusions: The majority of patients with DAPSA-LDA and active psoriasis after one year has a good HRQoL. However, a proportion of these patients still experiences considerable skin burden. We recommend rheumatologists to continue assessing and treating psoriasis to reduce skin burden in PsA patients who achieved musculoskeletal low disease activity.

Objectives: The use of long-term corticosteroids during pregnancy has been growing over the past decades. Corticosteroids can be given when an auto-inflammatory disease like rheumatoid arthritis (RA) is too active. Several studies have shown that long-term corticosteroids use in pregnancy is associated with maternal and fetal adverse outcomes, like preeclampsia, shorter gestational age, lower birth weight, and rapid catch-up growth. These last two outcomes could influence the insulin resistance later in life. Our objective was to investigate whether prednisone use in pregnant women with RA induces insulin resistance in offspring., Methods: One hundred three children were included after their mother had participated in a prospective cohort study on RA and pregnancy. Forty-two children were in utero exposed to prednisone and 61 were non-exposed. To assess insulin resistance, we measured homeostasis model of assessment insulin resistance (HOMA-IR) and serum adiponectin and lipid levels, corrected for body fat distribution., Results: An average of 6 mg prednisone on a daily use gave no difference in mean HOMA-IR (SD) between the children who were prednisone-exposed in utero (1.10 (0.84)) and those non-exposed (1.09 (0.49)). No difference was found in mean adiponectin level, body fat distribution, or lipid levels such as total cholesterol, fasting triglyceride, or high-density lipoprotein., Conclusion: Children who are prednisone-exposed in utero (low dose) have no increased risk for insulin resistance at the age of approximately 7 years. These findings are reassuring because the prednisone use during pregnancy is increasing worldwide. Further research has to be performed to evaluate if the insulin resistance remains absent in the future. Key Points • What is already known on this topic-long-term corticosteroids use in pregnancy is associated with fetal adverse outcomes, like lower birth weight and rapid catch-up growth which can influence the insulin resistance later in life. • What this study adds-long-term corticosteroids use in pregnant women with rheumatoid arthritis has no increased risk for insulin resistance in the offspring. • How this study might affect research, practice, or policy-findings are reassuring because prednisone use during pregnancy is increasing worldwide. Further research should evaluate if the insulin resistance remains absent in the future., (© 2022. The Author(s).)

Aims: To evaluate the number and nature of reported congenital malformations (CMs) after intrauterine exposure to non-tumour necrosis factor inhibitor biologics (non-TNFi biologics) compared to certolizumab pegol (CZP)., Methods: A retrospective comparative study was conducted in the EudraVigilance (EV) database. A safe biologic (CZP) was considered as the reference group. Odds ratios (ORs) for CMs were calculated for each non-TNFi biologic (including abatacept, anakinra, belimumab, ixekizumab, rituximab, secukinumab, tocilizumab, ustekinumab and vedolizumab), versus CZP (quantitative assessment). Then, CM patterns were reviewed in consultation with a clinical geneticist (qualitative assessment)., Results: ORs were not statistically significant except for belimumab and vedolizumab (similar in magnitude). Except for vedolizumab, no specific CM patterns were observed for the included non-TNFi biologics. Three cases of corpus callosum agenesis (CCA) were identified for vedolizumab (versus none in CZP and other investigated non-TNFi biologics). Two of the CCA cases were associated with other neurological CMs (one cerebral ventriculomegaly with microcephaly and one polymicrogyria). This may indicate that these CCAs are related to undiagnosed genetic alterations or are associated with the underlying maternal disease, although a definite relationship with vedolizumab exposure cannot be ruled out., Conclusion: No special safety signal was identified regarding the occurrence of CMs after exposure to abatacept (n = 64), anakinra (n = 20), belimumab (n = 93), ixekizumab (n = 29), rituximab (n = 57), secukinumab (n = 128), tocilizumab (n = 124) and ustekinumab (n = 215). Regarding observed CCAs in the vedolizumab group (n = 113), no firm conclusions can be made based on available information., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To determine the diagnostic performance and clinical utility of the Rotterdam Early Arthritis Cohort (REACH) and the Clinical Arthritis Rule (CARE) referral rules in an independent population of unselected patients from primary care., Methods: This study consisted of adults who were suspected of the need for referral to a rheumatologist by their general practitioner. Diagnostic accuracy measures and a net benefit approach were used to compare both rules to usual care for recognizing inflammatory arthritis and inflammatory rheumatic diseases (IRDs). Using the least absolute shrinkage and selection operator method and cross-validation we created an optimal prediction rule for IRD., Results: This study consisted of 250 patients, of whom 42 (17%) were diagnosed with inflammatory arthritis and 55 (22%) with an IRD 3 months after referral. Considering inflammatory arthritis, the area under the receiver operating characteristic curve (AUC) was 0.72 (95% confidence interval [95% CI] 0.64-0.80) for REACH and 0.82 (95% CI 0.75-0.88) for CARE. Considering IRD, the AUC was 0.66 (95% CI 0.58-0.74) for REACH and 0.76 (95% CI 0.69-0.83) for CARE. CARE was of highest clinical value when compared to usual care. The composite referral rule for IRD of 10 parameters included sex, age, joint features, acute onset of symptoms, physical limitations, and duration of symptoms (AUC 0.82 [95% CI 0.75-0.88])., Conclusion: Both validated rules have a net benefit in recognizing inflammatory arthritis as well as IRD compared to usual care, but CARE shows superiority over REACH. Although the composite referral rule indicates a greater diagnostic performance, external validation is needed., (© 2021 American College of Rheumatology.)

Objective: Rheumatologists play a pivotal role in the management of patients with psoriatic arthritis (PsA). Due to time constraints during clinic visits, the skin may not receive the attention needed for optimal patient outcome. Therefore, the aim of this study was to select a set of core questions that can help rheumatologists in daily rheumatology clinical practice to identify patients with PsA with a high skin burden., Methods: Baseline data from patients included in the Dutch South West Psoriatic Arthritis (DEPAR) cohort were used. Questions were derived from the Skindex-17 and Dermatology Life Quality Index (DLQI) questionnaires. Underlying clusters of questions were identified with an exploratory principal component analysis (PCA) with varimax rotation, after which a 2-parameter logistic model was fitted per cluster. Questions were selected based on their discrimination and difficulty. Subsequently, 2 flowcharts were made with categories of skin burden severity. Clinical considerations were specified per category., Results: In total, 413 patients were included. The PCA showed 2 underlying clusters: a psychosocial domain and a domain assessing physical symptoms. We selected these 2 domains. The psychosocial domain contains 3 questions and specifies 4 categories of skin burden severity. The physical symptoms domain contains 2 questions and categorizes patients in 1 out of 3 categories., Conclusion: We have selected a set with a maximum of 5 questions that rheumatologists can easily implement in their consultation to assess skin burden in patients with PsA. This practical guide makes the assessment of skin burden more accessible to rheumatologists and can aid in clinical decision making., (Copyright © 2022 by the Journal of Rheumatology.)

Objectives: Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA., Methods: We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA., Results: In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = <0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015]., Conclusions: This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Psoriasis impacts health-related quality of life (HRQoL) in PsA patients. However, this is not adequately measured with a general HRQoL questionnaire. The aim of this study was to quantify the degree of psoriasis evolution in PsA patients over the first year of follow-up and to evaluate whether the impact of psoriasis on HRQoL can be adequately measured with a dermatology-specific HRQoL questionnaire., Methods: Data were used from PsA patients in the Dutch south west Early Psoriatic Arthritis cohort. Psoriasis severity was measured with the Psoriasis Area and Severity Index (PASI). Dermatology-specific HRQoL was assessed with the Skindex-17 questionnaire. We used a Sankey diagram to illustrate the evolution of psoriasis severity during the first year of follow-up. To assess the association between psoriasis severity and the symptoms and psychosocial subscale of the Skindex-17, a linear regression analysis with hierarchical variable selection and zero-inflated negative binominal regression analysis were performed, respectively., Results: We included 644 patients; 109 (17%) patients had no psoriasis (PASI = 0), 456 (71%) had mild psoriasis (PASI < 7), 56 (9%) had moderate psoriasis (PASI 7-12) and 23 (4%) had severe psoriasis (PASI > 12). Psoriasis severity did not fluctuate much during the first year. PASI was significantly associated with both subscales of the Skindex-17 at baseline and 12 months., Conclusion: Psoriasis severity in PsA patients is mostly mild but impacts HRQoL when measured using a dermatology-specific HRQoL questionnaire. For optimal management of PsA patients, we recommend rheumatologists acquire information on skin burden by using a dermatology-specific HRQoL questionnaire., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: The impact of inflammatory arthritis (IA) on male fertility remains unexplored. Our objective was to evaluate the impact of IA on several male fertility outcomes; fertility rate (number of biological children per man), family planning, childlessness and fertility problems., Methods: We performed a multicentre cross-sectional study (iFAME-Fertility). Men with IA 40 years or older who indicated that their family size was complete were invited to participate. Participants completed a questionnaire that included demographic, medical and fertility-related questions. To analyse the impact of IA on fertility rate, patients were divided into groups according to the age at the time of their diagnosis: ≤30 years (before the peak of reproductive age), between 31 and 40 years (during the peak) and ≥41 years (after the peak)., Results: In total 628 participants diagnosed with IA were included. Men diagnosed ≤30 years had a lower mean number of children (1.32 (SD 1.14)) than men diagnosed between 31 and 40 years (1.60 (SD 1.35)) and men diagnosed ≥41 years (1.88 (SD 1.14)).This was statistically significant (p=0.0004).The percentages of men diagnosed ≤30 and 31-40 years who were involuntary childless (12.03% vs 10.34% vs 3.98%, p=0.001) and who reported having received medical evaluations for fertility problems (20.61%, 20.69% and 11.36%, p=0.027) were statistically significant higher than men diagnosed ≥41 years., Conclusions: This is the first study that shows that IA can impair male fertility. Men diagnosed with IA before and during the peak of reproductive age had a lower fertility rate, higher childlessness rate and more fertility problems. Increased awareness and more research into the causes behind this association are urgently needed., Competing Interests: Competing interests: LFPG Consultant of: Galapagos, MRK Consultant of: Novartis, Grant/research support from: Novartis, RJEMD Speakers bureau: UCB, Roche, Abbvie, Genzyme, Novartis, Consultant of: Galapagos, Grant/research supportfrom: UCB., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To compare (sustained) DMARD-free remission rates((S)DFR), defined as respectively ≥6 months and >1 year, after 2 and 5 years between three clinical arthritis phenotypes; undifferentiated arthritis(UA), autoantibody-negative(RA-) and positive rheumatoid arthritis(RA+)., Methods: All UA(n = 130), RA-(n = 176) and RA + (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. (S)DFR comparisons between phenotypes after 2 and 5 years were performed with Logistic regression. Medication use and early and late flares(DAS ≥ 2.4), respectively defined as < 12 and >12 months after reaching DFR, were also compared. Cox proportional hazard models were used to evaluate potential predictors for (S)DFR., Results: Within 2 and 5 years less DFR was seen in RA + (17.2-25.7%), followed by RA-(28.4-42.1%) and UA patients(43.1-58.5%). This also applied for SDFR within 2 and 5 years (respectively 7.6% and 21.4%; 20.5% and 38.1%; and 35.4% and 55.4%). A flare during tapering was seen in 22.7% of patients. Of the patients in DFR 7.5% had an early flare and 3.4% a late flare. Also more treatment intensifications occurred in RA+ compared with RA- and UA. We found that higher baseline DAS, ACPA positivity, BMI and smoking were negatively associated with (S)DFR, while clinical phenotype(reference RA+), short symptom duration(<6 months) and remission within 6 months were positively associated., Conclusions: (Long-term) clinical outcomes differ between undifferentiated arthritis, autoantibody-negative and positive rheumatoid arthritis(RA). These data reconfirm that RA can be subdivided into aforementioned clinical phenotypes and that treatment might be stratified upon these phenotypes, although validation is needed., Trial Registration: ISRCTN, https://www.isrctn.com/, ISRCTN26791028., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To compare patient-reported outcome (PRO) domains between three arthritis phenotypes [undifferentiated arthritis (UA), autoantibody-negative RA (RA-) and autoantibody-positive RA (RA+)] at diagnosis, after 2 years and over time., Methods: All UA (n = 130), RA- (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were used. PRO comparisons between phenotypes at baseline and after 2 years were performed with analysis of variance, while a linear mixed model compared them over time. Effect sizes were weighted against the minimal clinically important differences (MCIDs) for each PRO., Results: RA- patients had a higher disease burden compared with RA+ and UA. At baseline and after 2 years, RA- patients had more functional impairment and a poorer Physical Component Summary (PCS) compared with the other phenotypes, while they only scored worse for general health and morning stiffness duration at baseline. The MCIDs were exceeded at baseline, except for functional ability between RA+ and UA, while after 2 years only the MCID of the PCS was exceeded by RA- compared with UA and RA. After 2 years the PROs of all phenotypes improved, but PROs measuring functioning were still worse compared with the general population, even when patients had low disease activity., Conclusion: RA- patients had the highest disease burden of all phenotypes. Although most patients have low disease activity after treatment, all clinical phenotypes still have a similar significant impact on patients' lives, which is mainly physical. Therefore it is important to assess and address PROs in daily practice because of persistent disease burden despite low disease activity., Trial Registration: ISRCTN26791028., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: Management of early arthritis is based upon early recognition of individuals at high risk of developing persistent arthritis. Therefore, this study investigates whether the number of risk factors for persistent disease or treatment determines the clinical course of early arthritis by comparing the chance at (sustained) DMARD-free remission ((S)DFR) after 2 years follow-up., Methods: Data from the tREACH trial, a stratified single-blinded multicentre strategy trial with a treat-to-target approach were used. We selected all patients with ≥1 swollen joint who did not fulfil 1987 and/or 2010 criteria for RA. The number of risk factors present; autoantibody-positivity, polyarthritis (>4), erosive disease and elevated acute phase reactants, determined risk group stratification. Multivariate logistic regression analyses were performed with (S)DFR as dependent variables and baseline disease activity score (DAS), treatment, symptom duration and number of risk factors present as independent variables., Results: In total, 130 early arthritis patients were included and respectively 31, 66 and 33 had 0, 1 and ≥2 risk factors present. DFR rates were respectively 74%, 48% and 45% for early arthritis patients with 0, 1 and ≥2 risk factors present. In accordance SDFR rates were 61%, 32% and 30%. In our logistic model (S)DFR was not influenced by the initial treatment strategies when stratified for risk groups., Conclusion: The chance at (S)DFR in early arthritis diminishes when more risk factors are present, which is irrespective of the given initial treatment. Our data point out to a stratified management approach in early arthritis based on their risk profile, but validation is needed., Trial Registration: ISRCTN registry: ISRCTN26791028 (http://www.isrctn.com/ISRCTN26791028)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

We aim to explore real-world biological survival stratified for discontinuation reason and determine its influenceability in rheumatoid arthritis (RA) patients. Data from the local pharmacy database and patient records of a university hospital in the Netherlands were used. RA patients who started a biological between 2000 and 2020 were included. Data on age, anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) status, presence of erosions, gender, body mass index, time to first biological, biological survival time, use of csDMARDs, and discontinuation reasons were collected. Of the included 318 patients, 12% started their first biological within 6 months after diagnosis. The median time to first biological was 3.6 years (95% CI, 1.0-7.2). The median survival of the first- and second-line biological was respectively 1.7 years (95% CI, 1.3-2.2) and 0.8 years (95% CI, 0.5-1.0) (p = 0.0001). Discontinuation reasons for the first-line biological were ineffectiveness (47%), adverse events (17%), remission (16%), pregnancy (30%), or patient preference (10%). Multivariable Cox regression analyses for discontinuation due to inefficacy or adverse events showed that concomitant use of csDMARDs (HR = 1.32, p < 0.001) positively while RF positivity negatively (HR = 0.82, p = 0.03) influenced biological survival. ACPA positivity was associated with the inability to discontinue biologicals after achieving remission (HR = 1.43, p = 0.023). Second-line TNF inhibitor survival was similar between patients with a primary and secondary non-response on the first-line TNF inhibitor (HR = 1.28, p = 0.34). Biological survival diminishes with the number of biologicals used. Biological survival is prolonged if patients use csDMARDs. RF was negatively associated with biological survival. ACPA was negatively associated with the inability to discontinue biologicals after achieving remission. Therefore, tailoring treatment based upon autoantibody status might be the first step towards personalized medicine in RA. Key Points • Prolonged biological survival is a surrogate for treatment effectiveness; however, an increasing amount of patients will taper treatment due to remission, and factors influencing biological survival based on separate reasons for discontinuation have not been explored. • We found that combining a biological DMARD with a conventional synthetic DMARD increases biological DMARD survival. Rheumatoid factor is negatively associated with biological survival. Anti-citrullinated protein antibody is negatively associated with the inability to discontinue the biological when remission was reached. • The first step towards personalized medicine might be tailoring of treatment based upon autoantibody status.

Aim: To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients., Materials and Methods: DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months., Results: Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs., Conclusion: No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-analyses are required., Competing Interests: The authors have declared that no competing interests exist.

The goals of this study were to examine whether machine-learning algorithms outperform multivariable logistic regression in the prediction of insufficient response to methotrexate (MTX); secondly, to examine which features are essential for correct prediction; and finally, to investigate whether the best performing model specifically identifies insufficient responders to MTX (combination) therapy. The prediction of insufficient response (3-month Disease Activity Score 28-Erythrocyte-sedimentation rate (DAS28-ESR) > 3.2) was assessed using logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting (XGBoost). The baseline features of 355 rheumatoid arthritis (RA) patients from the "treatment in the Rotterdam Early Arthritis CoHort" (tREACH) and the U-Act-Early trial were combined for analyses. The model performances were compared using area under the curve (AUC) of receiver operating characteristic (ROC) curves, 95% confidence intervals (95% CI), and sensitivity and specificity. Finally, the best performing model following feature selection was tested on 101 RA patients starting tocilizumab (TCZ)-monotherapy. Logistic regression (AUC = 0.77 95% CI: 0.68-0.86) performed as well as LASSO (AUC = 0.76, 95% CI: 0.67-0.85), random forest (AUC = 0.71, 95% CI: 0.61 = 0.81), and XGBoost (AUC = 0.70, 95% CI: 0.61-0.81), yet logistic regression reached the highest sensitivity (81%). The most important features were baseline DAS28 (components). For all algorithms, models with six features performed similarly to those with 16. When applied to the TCZ-monotherapy group, logistic regression's sensitivity significantly dropped from 83% to 69% ( p = 0.03). In the current dataset, logistic regression performed equally well compared to machine-learning algorithms in the prediction of insufficient response to MTX. Models could be reduced to six features, which are more conducive for clinical implementation. Interestingly, the prediction model was specific to MTX (combination) therapy response.

This study aimed to identify baseline metabolic biomarkers for response to methotrexate (MTX) therapy in rheumatoid arthritis (RA) using an untargeted method. In total, 82 baseline plasma samples (41 insufficient responders and 41 sufficient responders to MTX) were selected from the Treatment in the Rotterdam Early Arthritis Cohort (tREACH, trial number: ISRCTN26791028) based on patients' EULAR response at 3 months. Metabolites were assessed using high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Differences in metabolite concentrations between insufficient and sufficient responders were assessed using partial least square regression discriminant analysis (PLS-DA) and Welch's t -test. The predictive performance of the most significant findings was assessed in a receiver operating characteristic plot with area under the curve (AUC), sensitivity and specificity. Finally, overrepresentation analysis was performed to assess if the best discriminating metabolites were enriched in specific metabolic events. Baseline concentrations of homocystine, taurine, adenosine triphosphate, guanosine diphosphate and uric acid were significantly lower in plasma of insufficient responders versus sufficient responders, while glycolytic intermediates 1,3-/2,3-diphosphoglyceric acid, glycerol-3-phosphate and phosphoenolpyruvate were significantly higher in insufficient responders. Homocystine, glycerol-3-phosphate and 1,3-/2,3-diphosphoglyceric acid were independent predictors and together showed a high AUC of 0.81 (95% CI: 0.72-0.91) for the prediction of insufficient response, with corresponding sensitivity of 0.78 and specificity of 0.76. The Warburg effect, glycolysis and amino acid metabolism were identified as underlying metabolic events playing a role in clinical response to MTX in early RA. New metabolites and potential underlying metabolic events correlating with MTX response in early RA were identified, which warrant validation in external cohorts.

Introduction: Methotrexate (MTX) constitutes the first-line therapy in rheumatoid arthritis (RA), yet approximately 30% of the patients do not benefit from MTX. Recently, we reported a prognostic multivariable prediction model for insufficient clinical response to MTX at 3 months of treatment in the treatment in the Rotterdam Early Arthritis Cohort (tREACH), including baseline predictors: Disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ), erythrocyte folate, single-nucleotide polymorphisms (SNPs; ABCB1, ABCC3), smoking, and BMI. The purpose of the current study was (1) to externally validate the model and (2) to enhance the model's clinical applicability., Methods: Erythrocyte folate and SNPs were assessed in 91 early disease-modifying antirheumatic drug (DMARD)-naïve RA patients starting MTX in the external validation cohort (U-Act-Early). Insufficient response (DAS28 > 3.2) was determined after 3 months and non-response after 6 months of therapy. The previously developed prediction model was considered successfully validated in the U-Act-Early (validation cohort) if the area under the curve (AUC) of the receiver operating characteristic (ROC) was not significantly lower than in the tREACH (derivation cohort)., Results: The AUCs in U-Act-Early at three and 6 months were 0.75 (95% CI 0.64-0.85) and 0.71 (95% CI 0.60-0.82) respectively, similar to the tREACH. Baseline DAS28 > 5.1 and HAQ > 0.6 were the strongest predictors. The model was simplified by excluding the SNPs, while still classifying 73% correctly. Furthermore, interaction terms between BMI and HAQ and BMI and erythrocyte folate significantly improved the model increasing correct classification to 75%. Results were successfully implemented in Evidencio online platform assisting clinicians in shared decision-making to intensify treatment when appropriate., Conclusions: We successfully externally validated our recently reported prediction model for MTX non-response and enhanced its clinical application thus enabling its evaluation in a clinical trial., Trial Registration: The U-Act-Early is registered at ClinicalTrials.gov. number: NCT01034137. tREACH is registered retrospectively at ISRCTN registry, number: ISRCTN26791028 at 23 August 2007.

Background: Inflammatory autoimmune diseases are chronic diseases that often affect women of childbearing age. Therefore, detailed knowledge of the safety profile of medications used for management of inflammatory autoimmune diseases during pregnancy is important. However, in many cases the potential harmful effects of medications (especially biologics) during pregnancy (and lactation) on mother and child have not been fully identified., Objective: Our aim was to update the data on the occurrence of miscarriages and (major) congenital malformations when using biologics during pregnancy based on newly published articles. Additionally, we selected several different secondary outcomes that may be of interest for clinicians, especially information on adverse events in the use of a specific biologic during pregnancy., Material and Methods: A search was conducted from 1 January 2015 until 4 July 2019 in Embase.com, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar with specific search terms for each database. Selection of publications was based on title/abstract and followed by full text (double blinded, two researchers). An overview was made based on outcomes of interest. References of the included publications were reviewed to include and minimize the missing publications., Results: A total of 143 publications were included. The total number of cases ranged from nine for canakinumab to 4276 for infliximab. The rates of miscarriages and major congenital malformations did not show relevant differences from those rates in the general population., Conclusion: Despite limitations to our study, no major safety issues were reported and no trend could be identified in the reported malformations.

Background: Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment., Objective and Rationale: The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes., Search Methods: A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data., Outcomes: A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-α inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressive drug exposure was reported., Wider Implications: Evidence regarding the safety of immunosuppressive drugs in men with a wish to become a father is inconclusive. The lack of standardisation on how to evaluate and report male sexual function, fertility and reproduction as study outcomes in men exposed to immunosuppressive drugs is an important contributor to this result. Future research on this topic is needed and should be preferably done using standardised methods., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: Rheumatoid arthritis (RA) often affects women in their fertile age, and is known to compromise female fertility. Serum anti-Müllerian hormone (AMH) levels are a proxy for the total number of primordial follicles, and a reliable predictor of the age at menopause. Our objective was to study the longitudinal intra-individual decline of serum AMH levels in female RA patients., Methods: Female RA patients from a nationwide prospective cohort (2002-2008) were re-assessed in 2015-2016. Serum AMH levels were measured using the picoAMH assay and compared with healthy controls. A linear mixed model (LMM) was built to assess the effect of RA-related clinical factors on the decline of AMH levels., Results: A group of 128 women were re-assessed at an age of 42.6±4.4 years, with a median disease duration of 15.8 (IQR 12.7-21.5) years. The time between first and last AMH assessments was 10.7±1.8 (range 6.4-13.7) years. Participants represented a more fertile selection of the original cohort. At follow-up, 39% of patients had AMH levels below the 10th percentile of controls (95% CI 31% to 48%), compared with 16% (95% CI 9.3% to 22%) at baseline. The LMM showed a significant decline of AMH with increasing age, but no significant effect of RA-related factors on AMH., Conclusion: AMH levels in RA patients showed a more pronounced decline over time than expected, supporting the idea that in chronic inflammatory conditions, reproductive function is compromised, resulting in a faster decline of ovarian function over time and probably an earlier age at menopause., Competing Interests: Competing interests: JB, JMWH and JAV declare no conflicts of interests. RJEMD has received an unrestricted research grant from UCB Pharma BV. JSEL has received unrestricted research grants from the following companies (in alphabetical order) Ferring, Merck Sharpe and Dome, Merck Serono, Organon, Shering Plough and Serono., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Interleukin-17A (IL-17A) and tumor necrosis factor (TNF) contribute to the pathogenesis of psoriatic arthritis (PsA). However, their functional relationship in PsA synovitis has not been fully elucidated. Additionally, although CD8+ T cells in PsA have been recognized via flow cytometry as a source of IL-17A production, it is not clear whether CD8+ T cells secrete IL-17A under more physiologically relevant conditions in the context from PsA synovitis. This study was undertaken to clarify the roles of IL-17A and TNF in the synovial fluid (SF) from patients with PsA and investigate the impact of CD8+ T cells on IL-17A production., Methods: IL-17A+ T cells were identified by flow cytometry in SF samples from 20 patients with active PsA, blood samples from 22 treatment-naive patients with PsA, and blood samples from 22 healthy donors. IL-17A+ T cells were sorted from 12 PsA SF samples and stimulated using anti-CD3/anti-CD28 or phorbol myristate acetate (PMA) and ionomycin ex vivo, alone (n = 3) or together with autologous monocytes (n = 3) or PsA fibroblast-like synoviocytes (FLS) (n = 5-6). To evaluate the differential allogeneic effects of neutralizing IL-17A and TNF, SF CD4+ T cells and PsA FLS cocultures were also used (n = 5-6)., Results: Flow cytometry analyses of SF samples from patients with PsA showed IL-17A positivity for CD4+ and CD8+ T cells (IL-17A, median 0.71% [interquartile range 0.35-1.50%] in CD4+ cells; median 0.44% [interquartile range 0.17-1.86%] in CD8+ T cells). However, only CD4+ T cells secreted IL-17A after anti-CD3/anti-CD28 activation, when cultured alone and in cocultures with PsA monocytes or PsA FLS (each P < 0.05). Remarkably, CD8+ T cells only secreted IL-17A after 4- or 72-hour stimulation with PMA/ionomycin. Anti-IL-17A and anti-TNF treatments both inhibited PsA synovitis ex vivo. Neutralizing IL-17A strongly inhibited IL-6 (P < 0.05) and IL-1β (P < 0.01), while anti-TNF treatment was more potent in reducing matrix metalloproteinase 3 (MMP-3) (P < 0.05) and MMP-13., Conclusion: CD8+ T cells, in contrast to CD4+ T cells, in SF specimens obtained from PsA patients did not secrete IL-17A following T cell receptor activation. Overlapping, but distinct, effects at the level of inflammatory cytokines and MMPs were found after neutralizing IL-17A or TNF ex vivo in a human model of PsA synovitis., (© 2020 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Methotrexate (MTX) is currently the recommended first-line therapy for treating psoriatic arthritis (PsA), despite lacking clear evidence. No estimates of efficacy of MTX in usual care and no clear MTX responsive clinical or laboratory variables are currently available. This study describes the response to MTX monotherapy in newly diagnosed patients with PsA in usual care. Second, we compared clinical variables and cytokine profiles in patients responding and not responding to MTX monotherapy., Methods: We used data collected in the Dutch southwest Early Psoriatic Arthritis cohoRt study to select patients with PsA with oligoarthritis or polyarthritis, and at least 1 year follow-up. We analysed disease activity at 6 months of patients who started MTX monotherapy and still used MTX monotherapy 1 year after diagnosis. Cytokine profiles were determined at baseline and after 3 and 6 months with a bead-based multi-immunoassay., Results: We identified 219 patients of which 183 (84%) patients started MTX monotherapy within 6 months after diagnosis. 90 patients used MTX monotherapy throughout the first year of which 44 patients (24%) reached minimal disease activity(MDA) at 6 months, decreasing to 33 patients (18%) after 1 year. Non-responders had significantly higher concentrations of interleukin (IL) 23 and IL-10 before and during MTX therapy., Conclusions: Our results showed that only 18% of patients with PsA are in sustained MDA after 1 year of MTX monotherapy and non-responders more often had IL-23-driven disease. Our results indicate the need for more treat-to-target and personalised therapy strategies in PsA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To describe parenting disability postpartum in patients with rheumatoid arthritis (RA) using the Parenting Disability Index and to determine early in pregnancy which patients will face parenting problems postpartum., Methods: Data were collected from a prospective study on pregnancy and RA (Pregnancy induced Amelioration of Rheumatoid Arthritis study). Postpartum visits were performed at 6, 12 and 26 weeks after delivery. Domains causing parenting difficulties were identified. A multivariate logistic regression model to identify which patients develop parenting disabilities postpartum with patient characteristics in the first trimester as covariates was performed., Results: 148 patients were eligible for this study. The domains carrying, hygiene, feeding, getting up and down, and household/shopping were frequently scored as difficult. Maintaining discipline, taking care of the children when sick, listening and having other children over caused the least problems. 30.1% of patients with RA report low parenting disability, 30.9% reports intermediate disability and 39.0% reports high disability. Patients with a low Health Assessment Questionnaire (HAQ)-score in the first trimester (OR 9.2, 95% CI 3.0 to 27.7, p<0.001) and low disease activity in the first trimester (Disease Activity Score 28-joint count C reactive protein<3.2) (OR 4.8, 95% CI 1.8 to 12.9, p=0.002) were likely to report low parenting disability postpartum. Patients with a longer disease duration (OR 0.87, 95% CI 0.79 to 0.95, p=0.003) were less likely to report low parenting disability postpartum. A high HAQ-score in the first trimester (OR 4.54, 95% CI 1.99 to 10.34, p<0.001) and erosive disease (OR 2.32, 95% CI 1.00 to 5.35, p=0.049) increased the risk of high parenting disability postpartum., Conclusion: Physical domains of parenting postpartum are most commonly affected in patients with RA. When counselling patients with RA, a HAQ-score in the first trimester is the most reliable marker to identify patients that develop parenting disability after delivery., Competing Interests: Competing interests: RJEMD received an unrestricted grant from UCB Pharma., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: Information about the possible effect of rheumatic diseases on male sexual function and reproduction (sexual health) is scarce and difficult to summarize. Factors known to impair sexual health, such as inflammation, medication use and hypogonadism can be present in a significant proportion of male patients with rheumatic diseases., Objectives: The objective of our study was to systematically review the literature for the influence of paternal rheumatic disease on sexual health, such as sexual function, reproductive hormones, male fertility, pregnancy and offspring outcomes., Data Sources: English language articles identified through Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Google Scholar and the Clinical trial registries of Europe and the USA published until February 2019., Study Appraisal and Synthesis Methods: Literature was synthesized in narrative form and in summary tables. Outcomes were categorized as: sexual function, reproductive hormones, fertility and pregnancy and offspring outcomes. Results are presented per category and per disease., Results: 9735 articles were identified with our search strategy. After removal of duplicates, excluding articles by screening titles and abstracts and assessing eligibility by reading 289 fulltext articles, 87 articles fulfilled the eligibility criteria. All included studies enrolled patients diagnosed with a rheumatic disease and had results at least on one of the outcome categories. Sexual function was the most common category, followed by reproductive hormones, fertility and pregnancy and offspring outcomes. Sexual function is impaired in a high proportion of patients with rheumatic diseases. This was statistically significant in most of the studies where a control group was available. Clinically relevant abnormalities in reproductive hormones were mainly identified in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and a positive correlation with disease activity were reported. Semen quality in men with rheumatic diseases can be impaired in patients with SLE, SpA, sarcoidosis, BD and MWS. Sperm count and motility were the most common semen quality parameters affected. No negative effect of paternal RA and vasculitis on pregnancy outcomes were reported in 3 studies. No studies reporting the effect of paternal disease on offspring outcomes were identified., Limitations: Most of the studies included in this review suffer from an inconsistent methodological quality, definitions of outcomes varied in several studies, a wide variety of screening questionnaires and/or diagnostic tools were used and results might only apply to the specific populations that were studied., Conclusions: This systematic review suggests that sexual health is impaired in men with rheumatic diseases. The degree and extent of sexual health impairment vary per disease. More research is needed to fully understand the link between rheumatic diseases and impaired male sexual health. Meanwhile, rheumatologists should be aware of this association and discuss it with their patients., Implications of Key Findings: Sexual health of men with rheumatic diseases can be impaired by the disease itself. Especially in men trying to conceive, information on sexual function, reproductive hormones and sperm quality are needed to identify these problems. Treatment resulting in lower disease activity can improve overall sexual health in man with rheumatic diseases and facilitate their journey to fatherhood., Systematic Review Registration Number: PROSPERO 2018 CRD42018099845., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment., Methods: Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS≤2.4 and SJC≤1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics., Results: A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ, and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare., Conclusion: A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: The effects of biologics on reproduction/lactation are mostly unknown although many patients that receive biologics are women of reproductive age. The first objective of this study was to investigate the publicly available data on pregnancy/lactation before and after marketing authorization in Europe of biologics for the indications of rheumatologic inflammatory autoimmune diseases and inflammatory bowel disease. Secondary objectives included the assessment of the clinical relevance of the provided data and comparison of initial and post-authorization data., Methods: Initial and post-authorization data were extracted from the European Public Assessment Reports and the latest versions of Summary of Product Characteristics using publicly available documents on the European Medicines Agency's website. Four sections were categorized regarding pregnancy outcomes: pre-clinical/animal studies, human female fertility, pregnancy-related outcomes and congenital malformations in the human fetus. Three sections were categorized regarding lactation outcomes: pre-clinical/animal studies, excretion in human breast milk and absorption in children through breastfeeding. The clinical applicability of each category was scored by specified criteria, based on scientific literature, and further as defined by the authors., Results: For the 16 included biologics, post-authorization data were delivered only for adalimumab, certolizumab pegol, etanercept and infliximab. For the 12 remaining biologics limited data on pregnancy and lactation during the post-marketing period of 2-21 years were available., Conclusions: In this article several suggestions are provided for improving a multidisciplinary approach to these issues. The initiation of suitable registries by marketing authorization holders and data transparency for clinicians and academics are highly endorsed., (© 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: Many factors influence a patient's preference in engaging in shared decision making (SDM). Several training programs have been developed for teaching SDM to physicians, but none of them focused on the patients' preferences. We developed an SDM training program for rheumatologists with a specific focus on patients' preferences and assessed its effects., Methods: A training program was developed, pilot tested, and given to 30 rheumatologists. Immediately after the training and 10 weeks later, rheumatologists were asked to complete a questionnaire to evaluate the training. Patients were asked before and after the training to complete a questionnaire on patient satisfaction., Results: Ten weeks after the training, 57% of the rheumatologists felt they were capable of estimating the need of patients to engage in SDM, 62% felt their communication skills had improved, and 33% reported they engaged more in SDM. Up to 268 patients were included. Overall, patient satisfaction was high, but there were no statistically significant differences in patient satisfaction before and after the training., Conclusion: The training was received well by the participating rheumatologists. Even in a population of rheumatologists that communicates well, 62% reported improvement. The training program increased awareness about the principles of SDM in patients and physicians, and improved physicians' communicative skills, but did not lead to further improvement in patients' satisfaction, which was already high.

Background: A substantial number of patients with chronic low back pain (CLBP) have axial spondyloarthritis (axSpA), but early recognition of these patients is difficult for general practitioners (GPs). The Case Finding Axial Spondyloarthritis (CaFaSpA) referral strategy has shown to be able to identify patients with CLBP at risk for axSpA, but its impact on clinical daily practice is yet unknown., Objective: To assess the effect of the CaFaSpA referral strategy on pain caused by disability in primary care patients with CLBP., Methods: Within this clustered randomized controlled trial 93 general practices were randomized to either the CaFaSpA referral model (intervention) or usual primary care (control). In each group primary care patients between 18 and 45 years with CLBP were included. The primary outcome was disability caused by CLBP, measured with the Roland Morris Disability Questionnaire (RMDQ) at baseline and four months. Secondary outcome was the frequency of new axSpA diagnosis. Descriptive analyses were performed, and a linear mixed-effects model was used., Results: In total 679 CLBP patients were included of which 333 patients were allocated to the intervention group and 346 to the control group. Sixty-four percent were female and mean age was 36.2 years. The mean RMDQ score at baseline was 8.39 in the intervention group and 8.61 in the control group. At four months mean RMDQ score was 7.65 in the intervention group and 8.15 in the control group. This difference was not statistically significant (p = 0.50). Six (8%) out of the 75 finally referred patients, were diagnosed with axSpA by their rheumatologist., Conclusions: The CaFaSpA referral strategy for axSpA did not have an effect on disability after four months caused by CLBP. However, the strategy is able to detect the axSpA patient within the large CLBP population sufficiently. Trial registration number: NCT01944163, Clinicaltrials.gov., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To compare responsiveness and longitudinal validity of Disease Activity Score 28 (DAS28), Disease Activity index for PSoriatic Arthritis (DAPSA), Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), GRAppa Composite scorE (GRACE) and Minimal Disease Activity (MDA) in usual care PsA patients, within 1 year after diagnosis., Methods: Data collected in the Dutch southwest early PsA cohort (DEPAR) were used. Responsiveness was assessed using effect size (ES), standardized response mean (SRM), and discrimination between different general health states. Longitudinal validity was tested using mixed models with outcomes health-related quality of life (HRQOL), productivity and disability., Results: Responsiveness was highest for PASDAS, with ES 1.00 and SRM 0.95, lowest for DAPSA, with ES 0.73 and SRM 0.71, and in between for DAS28, CPDAI and GRACE. Differences in general health were best discriminated with PASDAS and GRACE. Patients reporting stable or worsening general health could not be distinguished by DAS28 or CPDAI. Discrimination was better using DAPSA, but worse than when using PASDAS and GRACE. Longitudinal evolvement of HRQOL and productivity had the highest association with low disease activity according to GRACE, followed by PASDAS, MDA, DAPSA, DAS28, with the lowest association for CPDAI., Conclusion: PASDAS and GRACE were superior with respect to responsiveness, and together with MDA best related to longitudinal evolvement of HRQOL, productivity and disability. Responsiveness and longitudinal validity of most outcomes were inferior for DAS28, DAPSA and CPDAI. As alternatives to the continuous measure DAPSA, use of PASDAS or GRACE should be considered., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)