Search

ObjectiveAnkylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) is recommended over ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR) to assess disease activity in axial spondyloarthritis (axSpA). Although ASDAS-CRP and ASDAS-ESR are not interchangeable, the same disease activity cut-offs are used for both. We aimed to estimate optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs (1.3, 2.1, and 3.5) and investigate the potential improvement of level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states when applying these estimated cut-offs.MethodsWe used data from patients with axSpA from 9 European registries initiating a tumor necrosis factor inhibitor. ASDAS-ESR cut-offs were estimated using the Youden index. The level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states was compared against each other.ResultsIn 3664 patients, mean ASDAS-CRP was higher than ASDAS-ESR at both baseline (3.6 and 3.4, respectively) and aggregated follow-up at 6, 12, or 24 months (1.9 and 1.8, respectively). The estimated ASDAS-ESR values corresponding to the established ASDAS-CRP cut-offs were 1.4, 1.9, and 3.3. By applying these cut-offs, the proportion of discordance between disease activity states according to ASDAS-ESR and ASDAS-CRP decreased from 22.93% to 19.81% in baseline data but increased from 27.17% to 28.94% in follow-up data.ConclusionWe estimated the optimal ASDAS-ESR values corresponding to the established ASDAS-CRP cut-off values. However, applying the estimated cut-offs did not increase the level of agreement between ASDAS-ESR and ASDAS-CRP disease activity states to a relevant degree. Our findings did not provide evidence to reject the established cut-off values for ASDAS-ESR.

ABSTRACTIntroductionTNF inhibitors (TNFi) are in widespread use to treat a range of immune-mediated inflammatory diseases. However, the use of less expensive, biosimilar versions of these costly agents varies considerably around the world. Along with other Scandinavian countries, Norway has been successful in implementing the consistent clinical use of biosimilars rather than originator compounds.Areas coveredWe discuss the implementation of biosimilar TNFi in Norway, explain how this work was carried out over the past 10 years and highlight factors that have been key in securing their acceptance and use. This implementation is discussed in relation to the situation in other countries.Expert opinionThe Norwegian tender and procurement system has been important to lower the cost of TNFi. Importantly, the emergence of biosimilar alternatives has lowered the cost not just of biosimilar TNFi but also originators due to competition. The involvement of the clinical communities through expert advisory boards has been important in securing acceptance of biosimilars early on. We suggest that the Norwegian procurement and tender system for biologic drugs may serve as a model for other countries, but has to be adjusted and modified according to specific national health-care systems and national contextual factors.

ObjectiveTo compare the effectiveness of tumor necrosis factor inhibitors (TNFi) ± comedication and methotrexate (MTX) monotherapy between patients with adult juvenile idiopathic arthritis (JIA) and patients with rheumatoid arthritis (RA).MethodsAdult patients with JIA and RA were identified from the Norwegian Antirheumatic Drug Register (NOR-DMARD) register. Disease activity measurements at baseline, 3, 6, and 12 months were compared between patients with JIA and RA starting (1) TNFi and (2) MTX monotherapy, using age- and gender-weighted analyses. We calculated differences between JIA and RA in mean changes in Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI), among other disease activity measures. DAS28, CDAI, SDAI, and American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) remission rates at 3, 6, and 12 months, as well as 6- and 12-month Lund Efficacy Index (LUNDEX)-corrected rates, were calculated.ResultsWe identified 478 patients with JIA (TNFi/MTX monotherapy, n = 358/120) and 4637 patients with RA (TNFi/MTX monotherapy, n = 2292/2345). Patients with JIA had lower baseline disease activity compared to patients with RA across treatment groups. After baseline disease activity adjustment, there were no significant differences in disease activity change from baseline to 3, 6, and 12-months of follow-up between patients with JIA and RA for either treatment group. Twelve-month remission rates were similar between groups based on DAS28 (TNFi: JIA 55.2%, RA 49.5%; MTX monotherapy: JIA 45.3%, RA 41.2%) and ACR/EULAR remission criteria (TNFi: JIA 20.4%, RA 20%; MTX monotherapy: JIA 17%, RA 12.7%). Median drug survival (yrs) was similar for JIA and RA in both treatment groups (TNFi: JIA 1.2, RA 1.4; MTX monotherapy: JIA 1.3, RA 1.6).ConclusionTNFi and MTX monotherapy are effective in adult JIA, with similar effectiveness to that shown in RA.

There is a lack of real‐life studies on interleukin‐17 (IL‐17) inhibition in psoriatic arthritis (PsA). We assessed real‐life 6‐ and 12‐month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL‐17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan‐Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6‐month remission/LDA (LDA including remission) rates for the 28‐joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C‐reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12‐month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six‐month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12‐month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD‐naive patients, similar across time since diagnosis (<2/2–4/>4 years), and varied significantly across the European registries. In this large real‐world study on secukinumab treatment in PsA, 6‐ and 12‐month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD‐naive patients, were independent of time since diagnosis, and varied significantly across the European countries.

To investigate the longer‐term effects of secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in the MEASURE 1 study (up to 3 years) and the MEASURE 2 study (up to 2 years). Patients with active AS were randomized to secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous) and MEASURE 2 (150 mg subcutaneous). Patients were naive to treatment with anti–tumor necrosis factor (anti‐TNF‐naive) therapy or had an inadequate response/intolerance to anti‐TNF therapy (anti‐TNF‐IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored. Significant improvements in FACIT‐F scores from baseline were observed with secukinumab across both studies versus placebo at week 16 (P< 0.05). Improvements were sustained through week 156 (MEASURE 1) and week 104 (MEASURE 2). Significantly more patients reported fatigue responses (FACIT‐F improvement ≥4; observed data) with secukinumab 150 mg than with placebo at week 16 in both MEASURE 1 (P< 0.05) and MEASURE 2 (P< 0.01). Fatigue responses were achieved by 75.6% of patients receiving secukinumab at week 156 (MEASURE 1) and 81.4% at week 104 (MEASURE 2); these results were consistent in patients who were anti‐TNF‐naive (74.3% and 84.6%, respectively) and anti‐TNF‐IR (81.3% and 75.0%, respectively). Baseline characteristics did not predict improvement in fatigue consistently. Fatigue responses were moderately to strongly correlated with responses in several clinical measures, including the Assessment of SpondyloArthritis international Society (ASAS) 20%/40% improvement, ASAS5/6 responses, the Ankylosing Spondylitis Disease Activity Score with C‐reactive protein level, the Bath Ankylosing Spondylitis Disease Activity Index, and the Short Form 36 health questionnaire scores. Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti‐TNF exposure.

Many patients with systemic lupus erythematosus experience bone loss, according to a study of 75 SLE patients, 75 rheumatoid arthritis patients, and 75 healthy volunteers. Pre-menopausal women with SLE who take corticosteroids are especially vulnerable.

To compare levels of grip strength in individuals with hand osteoarthritis (OA) with normative values, and to examine how hand OA severity and other biopsychosocial factors are associated with grip strength. Levels of grip strength across age groups were compared with normative values from the general population in sex‐stratified analyses using 2‐sample t‐tests. Associations between radiographic hand OA severity (Kellgren/Lawrence sum score) in different joint groups and grip strength of the same hand were examined in 300 individuals from the Nor‐Hand study using linear regression. Analyses were repeated using markers of pain, demographic factors, comorbidities, and psychological and social factors as independent variables. We adjusted for age, sex, and body mass index. Individuals with hand OA had lower grip strength than the general population, especially in individuals age <60 years. In thumb base joints, increasing radiographic severity (range 0–8) and the presence of pain were associated with lower grip strength (β = –0.83 [95% confidence interval (95% CI) –1.12, –0.53] and β = –2.15 [95% CI –3.15, –1.16], respectively). Negative associations with grip strength were also found for women, low education, higher comorbidity index, and higher resting heart rate. Individuals with hand OA have lower grip strength than the general population. Our results support the idea that studies on thumb base OA should include grip strength as an outcome measure. However, other biopsychosocial factors should also be considered when the grip strength is being interpreted, because other factors such as sex, socioeconomic factors, physical fitness, and comorbidities are negatively associated with grip strength.

ObjectiveIn rheumatoid arthritis (RA), evidence regarding the effectiveness of a second biologic disease-modifying antirheumatic drug (bDMARD) in patients whose first-ever bDMARD was a non–tumor necrosis factor inhibitor (TNFi) bDMARD is limited. The objective of this study was therefore to assess the outcome of a second bDMARD (non-TNFi: rituximab [RTX], abatacept [ABA], or tocilizumab [TCZ], separately; and TNFi) after failure of a non-TNFi bDMARD as first bDMARD.MethodsWe identified patients with RA from the 5 Nordic biologics registers who started treatment with a non-TNFi as first-ever bDMARD but switched to a second bDMARD. For the second bDMARD, we assessed drug survival (at 6 and 12 months) and primary response (at 6 months).ResultsWe included 620 patients starting a second bDMARD (ABA 86, RTX 40, TCZ 67, and TNFi 427) following failure of a first non-TNFi bDMARD. At 6 and 12 months after start of their second bDMARD, approximately 70% and 60%, respectively, remained on treatment, and at 6 months, less than one-third of patients were still on their second bDMARD and had reached low disease activity or remission according to the Disease Activity Score in 28 joints. For those patients whose second bMDARD was a TNFi, the corresponding proportion was slightly higher (40%).ConclusionThe drug survival and primary response of a second bDMARD in patients with RA switching due to failure of a non-TNFi bDMARD as first bDMARD is modest. Some patients may benefit from TNFi when used after failure of a non-TNFi as first bDMARD.

To explore whether ultrasound‐detected gray‐scale synovitis and power Doppler activity in the interphalangeal and first carpometacarpal (CMC1) joints are associated with pain and physical function in patients with hand osteoarthritis (OA). A total of 290 patients with hand OA underwent an ultrasound examination of the bilateral interphalangeal and CMC1 joints. Using logistic regression analyses with generalized estimating equations, we examined whether grade 0–3 gray‐scale synovitis and power Doppler activity were associated with pain in the same joint. Using linear regression analyses, we examined whether the degree of inflammation was associated with numeric rating scale and Australian/Canadian (AUSCAN) Osteoarthritis Hand Index hand pain, AUSCAN physical function, and grip strength scores. Analyses were made separately for interphalangeal and CMC1 joints, and adjusted for age, sex, body mass index, psychosocial factors, use of analgesics, and presence of osteophytes. At joint level, increasing gray‐scale synovitis severity was associated with higher odds of pain upon palpation in both the interphalangeal (grade 2–3; odds ratio [OR] 3.17 [95% confidence interval (95% CI) 2.35, 4.28]) and CMC1 joints (grade 2–3; OR 4.40 [95% CI 2.10, 9.24]). Similar associations were found for power Doppler activity and joint pain in the previous 24 hours and 6 weeks. Power Doppler activity in CMC1 was also related to overall hand pain/physical function and lower grip strength. Inflammation in both the interphalangeal and CMC1 joints was associated with pain in the same joint. However, associations with hand pain, reduced physical function, and lower grip strength were only present for inflammation in the CMC1 joints, suggesting that lowering CMC1 inflammation is an important treatment target.

The tender joint count (TJC) is included in composite disease activity scores (CDAS) (the Disease Activity Score in 28 joints, the Clinical Disease Activity Index, and the Simplified Disease Activity Index). The impact of having predominantly tender joints was explored by use of the Tender‐Swollen Joint Count Difference (TSJD), and ultrasound (US) provided a measure of joint inflammation. The current study aimed to explore the cross‐sectional and longitudinal associations between the TSJD and a spectrum of outcome measures, including US scores in patients with established rheumatoid arthritis (RA) during follow‐up and while receiving treatment with biologic disease‐modifying antirheumatic drugs (bDMARDs). This was an observational study of 209 patients with established RA consecutively included upon initiation of bDMARD treatment and followed‐up with clinical, laboratory, and comprehensive US examinations at 0, 1, 2, 3, 6, and 12 months. Patients were categorized into 2 groups: those with predominantly tender joints (TSJD >0) and those with predominantly swollen joints (TSJD ≤0). Statistical analyses included Pearson's correlation coefficient, an independent samples t‐test, and regression analyses. The TJC had high correlations only with patient‐reported outcomes (PROMs) (P< 0.001). Levels from CDAS and PROMs were significantly higher (P< 0.001) at all visits in patients with TSJD >0 compared to those with TSJD <0. Laboratory markers and assessor's global visual analog scale scores were similar, and US sum scores were significantly lower (P< 0.001–0.03). The baseline TSJD positively predicted levels of all CDAS at 6 months (P< 0.001–0.019) but was a negative predictor of US sum scores (gray‐scale and power Doppler) at 6 and 12 months (P< 0.001). Patients with predominantly tender joints had higher CDAS but lower levels of inflammation as defined by US. These findings indicate that inclusion of the TJC in the CDAS may contribute to misleading information about inflammatory activity.

Background: In European axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) clinical registries, we aimed to investigate commonalities and differences in (1) set-up, clinical data collection; (2) data availability and completeness; and (3) wording, recall period, and scale used for selected patient-reported outcome measures (PROMs). Methods: Data was obtained as part of the EuroSpA Research Collaboration Network and consisted of (1) an online survey and follow-up interview, (2) upload of real-world data, and (3) selected PROMs included in the online survey. Results: Fifteen registries participated, contributing 33,948 patients (axSpA: 21,330 (63%), PsA: 12,618 (37%)). The reported coverage of eligible patients ranged from 0.5 to 100%. Information on age, sex, biological/targeted synthetic disease-modifying anti-rheumatic drug treatment, disease duration, and C-reactive protein was available in all registries with data completeness between 85% and 100%. All PROMs (Bath Ankylosing Spondylitis Disease Activity and Functional Indices, Health Assessment Questionnaire, and patient global, pain and fatigue assessments) were more complete after 2015 (68–86%) compared to prior (50–79%). Patient global, pain and fatigue assessments showed heterogeneity between registries in terms of wording, recall periods, and scale. Conclusion: Important heterogeneity in registry design and data collection across fifteen European axSpA and PsA registries was observed. Several core measures were widely available, and an increase in data completeness of PROMs in recent years was identified. This study might serve as a basis for examining how differences in data collection across registries may impact the results of collaborative research in the future.

Objective.To examine the validity of a modified Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire for assessment of pain in hand osteoarthritis (OA).Methods.The modified ICOAP-hand questionnaire was administered to 300 patients [89% female, median (interquartile range) age: 61 (57–66) yrs] in the Nor-Hand observational cohort study. The questionnaire was completed twice by 31 patients and test-retest reliability was assessed by intraclass correlation coefficients (ICC) for sum scores and weighted κ scores for individual items. Internal consistency was assessed by Cronbach’s alpha coefficient and item-total correlations. Correlations between the ICOAP-hand questionnaire, the Australian/Canadian Hand OA Index (AUSCAN) hand pain subscale, and pain on a numerical rating scale (NRS) were analyzed using Spearman correlation analyses.Results.We found a substantial overlap between constant and intermittent pain (46% reporting constant + intermittent pain and 33% reporting no pain). Test-retest reliability analysis of ICOAP-hand showed an ICC of 0.89 for the total scale and weighted κ values between 0.39–0.70 for the individual items. Principal component analysis revealed one component with an eigenvalue of 7.9, explaining 72% of the total variance. Cronbach’s alpha coefficient values > 0.93 and strong item-total correlations proved high internal consistency. ICOAP-hand was strongly correlated with NRS hand pain and the AUSCAN pain subscale.Conclusion.ICOAP-hand is a reliable pain index that correlates with other available pain questionnaires. However, our results indicate that constant and intermittent pain do not represent separate constructs in hand OA, questioning the usefulness of the 2 subscales. [ClinicalTrials.gov: NCT03083548]

To determine whether the comorbidity burden and co-existing comorbidities are cross-sectionally and/or longitudinally associated with pain and pain sensitization in a cohort study of people with hand OA.

Abstract Objectives--To examine relations between osteoporosis and low bone mass and demographic and clinical variables in patients with rheumatoid arthritis (RA), in an attempt to develop a data driven clinical [...]

Abstract Objective--To investigate factors associated with visiting a general practitioner (GP) for non-inflammatory musculoskeletal pain, and to examine whether these factors were affected by duration (chronic v non-chronic) or location [...]

Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with important pain‐related outcomes. The objective of this prospective study of established rheumatoid arthritis (RA) patients was to explore how pain catastrophizing was related to patient‐reported outcomes (PROs), composite scores, and assessments of inflammatory activity. RA patients starting biologic disease‐modifying antirheumatic drugs were examined at baseline and after 1, 2, 3, 6, and 12 months with PROs (joint pain/patient's global visual analog scale [VAS], modified Health Assessment Questionnaire, Rheumatoid Arthritis Impact of Disease score), clinical and laboratory assessments (tender/swollen joint count, assessor's global VAS, erythrocyte sedimentation rate/C‐reactive protein [CRP] level), ultrasound (US) (gray scale [GS]/power Doppler [PD] of 36 joints and 4 tendons), and pain catastrophizing. The composite scores for Disease Activity Score in 28 joints, Clinical Disease Activity Index, and Simplified Disease Activity Index were calculated. Statistical calculations included independent samples t‐test, paired samples t‐test, one‐way analysis of variance, Pearson's correlations, and linear and logistic regression. Of 209 patients included, 152 (72.7%) completed 12‐month followup. Pain catastrophizing, PROs, and clinical and inflammatory assessments decreased significantly (P< 0.001). Pain catastrophizing was strongly correlated with the PROs and composite scores (P< 0.001) but not with the inflammatory parameters (swollen joint count, CRP level, and GS/PD US). Patients with higher levels of pain catastrophizing had higher PROs and composite scores during the study (P< 0.001) but not inflammatory assessments. Baseline pain catastrophizing was negatively associated with achievement of remission at 6 and 12 months (P< 0.05). Pain catastrophizing was strongly associated with PROs and composite measures, but not with markers of inflammation. High levels of pain catastrophizing reduced the likelihood of achieving composite score remission and should be a factor to consider in a treat‐to‐target strategy.

Objective.To assess associations between cardiorespiratory fitness (CRF), measured as peak oxygen uptake (VO2peak), and cardiovascular disease (CVD) risk, measured by arterial stiffness, in patients with ankylosing spondylitis (AS).Methods.VO2peak was assessed by a maximal walking test on a treadmill. Arterial stiffness was measured noninvasively (Sphygmocor apparatus). Cross-sectional associations between VO2peak and arterial stiffness were analyzed using backward multivariable linear regression.Results.Among 118 participating patients, there were significant inverse associations between VO2peak and arterial stiffness, independent of traditional CVD risk factors and measures of disease activity.Conclusion.Reduced CRF may be related to increased risk of CVD in AS.

To explore the link between a patient acceptable symptom state (PASS) and patient‐perceived impact in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This was a cross‐sectional study of unselected patients with definite RA or PsA. Pain, functional capacity, fatigue, coping, and sleep disturbance were assessed using a numeric rating scale (0–10) and compared between patients in PASS or not (Cohen's effect sizes). The domains of health associated with PASS status were assessed by multivariate forward logistic regression, and PASS thresholds were determined using the 75th percentile method and receiver operating characteristic analyses. Among 977 patients (531 with RA, 446 with PsA), the mean ± SD age was 53.4 ± 13.2 years, mean ± SD disease duration was 11.2 ± 10.0 years, and 637 (65.8%) were women. In all, 595 patients (60.9%) were in PASS; they had lower symptom levels, and all domains of health except sleep disturbance discriminated clearly between patients in PASS or not (effect sizes 0.73–1.45 in RA and 0.82–1.52 in PsA). In multivariate analysis, less pain and better coping were predictive of being in PASS. Odds ratios were: RA pain 0.80 (95% confidence interval [95% CI] 0.67–0.96), PsA pain 0.63 (95% CI 0.52–0.75), RA coping 0.84 (95% CI 0.74–0.96), and PsA coping 0.83 (95% CI 0.71–0.97). The cutoffs of symptom intensity (range 0–10), corresponding to PASS for the 5 domains of health and the 2 diseases were similar, i.e., approximately 4–5. In RA and PsA, PASS was associated with the 5 domains of health analyzed, and in particular with less pain and better coping.

Patient‐physician discordance in global assessment of disease activity concerns one‐third of patients, but what does it reflect? We aimed to assess patient‐physician discordance in psoriatic arthritis (PsA) and patient‐reported domains of health (physical and psychological) associated with discordance. We analyzed the PsAID (Psoriatic Arthritis Impact of Disease), a cross‐sectional, multicenter European study of patients with PsA according to expert opinion. Patient global assessment (PGA) and physician global assessment (PhGA) were rated on a 0–10 numeric rating scale. Discordance was defined as the difference (PGA−PhGA) and as the absolute difference |PGA−PhGA| ≥3 points. Determinants of PGA−PhGA were assessed by a stepwise multivariate linear regression among 12 physical and psychological aspects of impact: pain, skin problems, fatigue, ability to work/leisure, functional incapacity, feeling of discomfort, sleep disturbance, anxiety/fear, coping, embarrassment/shame, social participation, and depressive affects. In 460 patients (mean ± SD age 50.6 ± 12.9 years, 52.2% female, mean ± SD disease duration 9.5 ± 9.5 years, mean ± SD Disease Activity Index for Psoriatic Arthritis score 30.8 ± 32.4, and 40.4% undergoing treatment with biologic agents), the mean ± SD PGA was higher than the mean PhGA, with a mean absolute difference of 1.9 ± 1.8 points. Discordance defined by |PGA−PhGA| ≥3 of 10 concerned 134 patients (29.1%), and 115 patients (85.8% of the patients with discordance) had PGA>PhGA. Higher fatigue (β = 0.14), lower self‐perceived coping (β = 0.23), and impaired social participation (β = 0.16) were independently associated with a higher difference (PGA−PhGA). Discordance concerned 29.1% of these patient/physician dyads, mainly by PGA>PhGA. Factors associated with discordance were psychological rather than physical domains of health. Discordance was more frequent in patients in remission, indicating more work is needed on the patient perspective regarding disease activity.

TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity.

Objective.Several aspects of rituximab (RTX) retreatment in rheumatoid arthritis (RA) need to be further elucidated. The aim of this study was to describe the effect of repeated courses of RTX on disease activity and to compare 2 retreatment strategies, fixed-interval versus on-flare retreatment, in a large international, observational, collaborative study.Methods.In the first analysis, patients with RA who received at least 4 cycles with RTX were included. In the second analysis, patients who received at least 1 RTX retreatment and for whom information about the strategy for retreatment was available were identified. Two retreatment strategies (fixed-interval vs on-flare) were compared by fitting-adjusted, mixed-effects models of 28-joint Disease Activity Score (DAS28) over time for first and second retreatment.Results.A total of 1530 patients met the eligibility criteria for the first analysis. Significant reductions of mean DAS28 between the starts of subsequent treatment cycles were observed (at start of first treatment cycle: 5.5; second: 4.3; third: 3.8; and fourth: 3.5), suggesting improved response after each additional cycle (p < 0.0001 for all pairwise comparisons). A total of 800 patients qualified for the second analysis: 616 were retreated on flare and 184 at fixed interval. For the first retreatment, the fixed-interval retreatment group yielded significantly better results than the on-flare group (estimated marginal mean DAS28 = 3.8, 95% CI 3.6–4.1 vs 4.6, 95% CI 4.5–4.7, p < 0.0001). Similar results were found for the second retreatment.Conclusion.Repeated treatment with RTX leads to further clinical improvement after the first course of RTX. A fixed-interval retreatment strategy seems to be more effective than on-flare retreatment.

Objective.To examine the 2-year disease course in patients with undifferentiated arthritis (UA) focusing on fulfillment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) classification criteria.Methods.Data were provided by the Norwegian Very Early Arthritis Clinic study, which included patients presenting with ≥ 1 swollen joint of ≤ 16 weeks’ duration. UA was defined as patients not fulfilling the 2010 ACR/EULAR RA criteria and who did not have a clinical diagnosis other than RA at baseline. The main outcome was fulfillment of the 2010 RA criteria. Secondary outcomes were disease-modifying antirheumatic drug (DMARD) use, resolution of synovitis without use of DMARD during followup, and final clinical diagnosis.Results.We included 477 patients with UA of whom 47 fulfilled the 2010 ACR/EULAR RA criteria during followup (UA-RA) and 430 did not (UA–non-RA). Of the UA-RA patients, 70% fulfilled the criteria within the first 6 months. UA-RA patients were older, more often positive for rheumatoid factor and anticitrullinated protein antibodies, female, and ever smokers, and they more often presented with polyarticular arthritis, small joint involvement, and a swollen shoulder joint. During followup, 53% of UA-RA patients vs 13% of UA-non-RA patients used DMARD (p < 0.001). Overall, 71% of patients with UA achieved absence of clinical synovitis at final followup without use of DMARD. The most frequent final clinical diagnosis was UA (61%).Conclusion.Only 9.8% of patients with UA fulfilled the 2010 RA criteria during 2-year followup. Small joint involvement and swollen shoulder joint were among the factors associated with RA development. In two-thirds of patients with UA, the arthritis resolved without use of DMARD.

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). 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

Fatigue is a frequently occurring symptom in patients with rheumatoid arthritis (RA). Our aims were to assess the level of reported fatigue in RA patients who had achieved remission or low disease activity after 6 months of treatment with disease‐modifying antirheumatic drugs (DMARDs), and to explore associations between fatigue and demographics, disease activity, and other patient‐reported outcomes in this patient group. A total of 2,193 RA patients (ages ≥18 years) starting either methotrexate (MTX) monotherapy or a tumor necrosis factor inhibitor in combination with MTX were retrieved from the Norwegian Disease‐Modifying Antirheumatic Drugs Register (NOR‐DMARD). At the 6‐month followup, 699 patients (31.9%) were in remission or in a low disease activity state. Bivariate and multivariate linear regression analyses were conducted, with the fatigue visual analog scale (VAS) at 6 months as the dependent variable. Age, sex, disease duration, treatment group, erythrocyte sedimentation rate (ESR), the swollen and tender joint count in 28 joints, the pain VAS score, and disability at baseline and at 6 months were tested as predictors of fatigue at 6 months. At 6 months, the median (25th, 75th percentile) level of fatigue was 20.0 mm (6.0, 43.0), and a fatigue VAS score of ≥40 mm was reported by 27.9% of patients. In the multivariate analysis, lower ESR and higher pain at baseline were statistically significant predictors of higher levels of fatigue (P< 0.001). In the multivariate cross‐sectional analysis at 6 months, younger age and greater pain were significantly associated with higher levels of fatigue (P< 0.001). Pain levels at baseline and at 6 months were associated with a higher level of fatigue. Patients in remission or in a low disease activity state may need nonpharmacologic interventions to manage their pain and fatigue.

Purpose: This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate. Methods: This review is the result of a multidisciplinary expert working group, organised by European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis. The recent literature was surveyed and the salient evidence synthetized. Results: The pathophysiological basis of RA (and other inflammatory rheumatic diseases) now strongly implicates the adaptive immune system in addition to innate mechanisms. The molecular effect of GCs and differential GC sensitivity is better understood, although exploiting this knowledge is still in its infancy. The newer treatment strategies of early and aggressive control of RA have gr eatly improved clinical outcomes, but improvements are still possible. Newer targeted anti-inflammatory drugs have made an important impact, yet they too are associated with numerous side effects. Discussion: Short durations of moderate doses of GCs are generally well tolerated and have a positive benefit/risk ratio. Patients should be assessed for fracture risk and bone preserving agents and be prescribed calcium and vitamin D supplementation. Conclusions: Within a strategy of a disease modifying approach to inflammatory disease, combination therapy including a GC is effective approach.

Objective.We evaluated the predictive value of these vascular biomarkers for cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA): aortic pulse wave velocity (aPWV), augmentation index (AIx), carotid intima-media thickness (cIMT), and carotid plaques (CP). They are often used as risk markers for CVD.Methods.In 2007, 138 patients with RA underwent clinical examination, laboratory tests, blood pressure testing, and vascular biomarker measurements. Occurrence of CVD events was recorded in 2013. Predictive values were assessed in Kaplan-Meier plots, log-rank, and crude and adjusted Cox proportional hazard (PH) regression analyses.Results.Baseline median age and disease duration was 59.0 years and 17.0 years, respectively, and 76.1% were women. CVD events occurred in 10 patients (7.2%) during a mean followup of 5.4 years. Compared with patients with low aPWV, AIx, cIMT, and without CP, patients with high aPWV (p < 0.001), high AIx (p = 0.04), high cIMT (p = 0.01), and CP (p < 0.005) at baseline experienced more CVD events. In crude Cox PH regression analyses, aPWV (p < 0.001), cIMT (p < 0.001), age (p = 0.01), statin (p = 0.01), and corticosteroid use (p = 0.01) were predictive of CVD events, while AIx was nonsignificant (p = 0.19). The Cox PH regression estimates for vascular biomarkers were not significantly altered when adjusting individually for demographic variables, traditional CVD risk factors, RA disease-related variables, or medication. All patients who developed CVD had CP at baseline.Conclusion.CP, aPWV, and cIMT were predictive of CVD events in this cohort of patients with RA. Future studies are warranted to examine the additive value of arterial stiffness and carotid atherosclerosis markers in CVD risk algorithms. Regional Ethical Committee approval numbers 2009/1582 and 2009/1583.