Global Assessment Of Disease Activity Research Articles

P200 Characterisation of remission in patients with rheumatoid arthritis treated with upadacitinib or comparators

Abstract Background Across all phase 3 studies, treatment with upadacitinib (UPA), a JAK1-selective inhibitor, was associated with significantly higher remission (REM) rates, compared to placebo (PBO) or active comparators, in RA patients who were methotrexate (MTX)-naive, had inadequate response to conventional synthetic (csDMARD-IR) or had inadequate response or intolerance to biologic DMARDs (bDMARD-IR). Methods REM definitions are based on composite scores of various individual assessments of disease activity. To determine the response to UPA on REM and component assessments, we assessed the proportions of patients achieving REM using multiple REM definitions, and the improvement in their respective individual components, compared to PBO or active comparators, in 3 different RA patient populations spanning a range of RA patient populations. Methods: Three phase 3 studies included patients who were MTX naïve (SELECT EARLY, n = 945), MTX-IR (SELECT COMPARE, n = 1629) and bDMARD-IR (SELECT BEYOND, n = 498). The proportion of patients achieving REM at Week 12 by 4 definitions (DAS28-CRP<2.6; CDAI <2.8; SDAI <3.3 and Boolean, defined as < 1 for TJC, SJC, patient’s global assessment of disease activity [PtGA], and CRP <1 mg/L) were determined. For each definition of REM, the mean change in each of the respective component scores was also assessed. Binary endpoints are based on Non-responder imputation (NRI), and continuous endpoints on mixed-effect model repeat measurement (MMRM). Comparisons were made between UPA-treated groups vs respective control arms (MTX, adalimumab [ADA] or PBO). Results Patient demographics and disease characteristics have been previously reported. 1-3 At 12 weeks, in EARLY and COMPARE, a significantly greater proportion of patients receiving UPA 15 mg or 30 mg QD achieved REM by all 4 definitions vs MTX, PBO or ADA (Table). In BEYOND, (a refractory population many of whom had inadequate response to multiple bDMARDs), a significantly greater proportion of patients receiving UPA 30mg achieved all REM definitions vs PBO within the first 12 weeks, with significantly greater proportions on UPA 15mg achieving DAS28-CRP<2.6 and Boolean REM. Rates of REM in BEYOND further increased through Wk 24 for both dose groups. Compared to respective control groups, patients receiving UPA 15 or 30 mg QD had significantly greater improvements in each REM disease component (except for PhGA vs ADA in COMPARE). Significantly more patients receiving UPA also achieved the required cutoffs on the individual components of Boolean REM compared to respective controls. Conclusion Significantly greater proportions of patients receiving UPA 15 or 30mg achieved REM by multiple definitions at 12 weeks compared to PBO, MTX or ADA. All disease activity components of each REM definition were significantly improved in patients receiving UPA compared to MTX or PBO, and all Boolean components were significantly improved in patients receiving UPA 15mg compared to ADA. Disclosures S. Hall: Grants/research support; AbbVie, BMS, Lilly, Janssen, Pfizer, UCB, Novartis. T. Takeuchi: Honoraria; Mitsubishi-Tanabe Pharma Corp, Janssen Pharma KK, Chugai Pharma, Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd, BMS, Daiichi Sankyo Company Ltd, Eli Lilly Japan KK, Pfizer Japan Inc. Grants/research support; Pfizer Japan Inc., Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corp, Nippon Kayaku Co., Ltd, Taisho Toyama Pharma, Takeda Pharma, AYUMI Pharma, Takahashi Industrial. G. Thomson: Consultancies; Amgen. Grants/research support; AbbVie. P. Emery: Grants/research support; Research grants and consulting fees from Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. B. Combe: Grants/research support; Consultancy fees from Abbvie, BMS, Jansen, Lilly, MSD, Pfizer, Roche Chugai, UCB. A. Everding: None. K. Pavelka: Honoraria; Honoraria for lectures and consultations from companies: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie. Y. Song: Corporate appointments; Employee of AbbVie. T. Shaw: Corporate appointments; Employee of AbbVie. A. Friedman: Corporate appointments; Employee of AbbVie. I. Song: Corporate appointments; Employee of AbbVie. E. Mysler: Grants/research support; Research grants and consulting fees from AbbVie, Lilly, Pfizer, Roche, BMS, Sandoz.

A Canadian evaluation framework for quality improvement in childhood arthritis: key performance indicators of the process of care

BackgroundThe evaluation of quality of care in juvenile idiopathic arthritis (JIA) is critical for advancing patient outcomes but is not currently part of routine care across all centers in Canada. The study objective is to review the current landscape of JIA quality measures and use expert panel consensus to define key performance indicators (KPIs) that are important and feasible to collect for routine monitoring in JIA care in Canada.MethodsThirty-seven candidate KPIs identified from a systematic review were reviewed for inclusion by a working group including 3 pediatric rheumatologists. A shortlist of 14 KPIs was then assessed using a 3-round modified Delphi panel based on the RAND/UCLA Appropriateness Method. Ten panelists across Canada participated based on their expertise in JIA, quality measurement, or lived experience as a parent of a child with JIA. During rounds 1 and 3, panelists rated each KPI on a 1–9 Likert scale on themes of importance, feasibility, and priority. In round 2, panelists participated in a moderated in-person discussion that resulted in minor modifications to some KPIs. KPIs with median scores of ≥ 7 on all 3 questions without disagreement were included in the framework.ResultsTen KPIs met the criteria for inclusion after round 3. Five KPIs addressed patient assessments: pain, joint count, functional status, global assessment of disease activity, and the clinical Juvenile Arthritis Disease Activity Score (cJADAS). Three KPIs examined access to care: wait times for consultation, access to pediatric rheumatologists within 1 year of diagnosis, and frequency of clinical follow-up. Safety was addressed through KPIs on tuberculous screening and laboratory monitoring. KPIs examining functional status using the Childhood Health Assessment Questionnaire (CHAQ), quality of life, uveitis, and patient satisfaction were excluded due to concerns about feasibility of measurement.ConclusionsThe proposed KPIs build upon existing KPIs and address important processes of care that should be measured to improve the quality of JIA care. The feasibility of capturing these measures will be tested in various data sources including the Understanding Childhood Arthritis Network (UCAN) studies. Subsequent work should focus on development of meaningful outcome KPIs to drive JIA quality improvement in Canada and beyond.

Indirect comparison of NSAIDs for ankylosing spondylitis: Network meta-analysis of randomized, double-blinded, controlled trials.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by lower back pain, enthesitis and asymmetrical peripheral arthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first-line drug treatment for AS. The aim of the present study was to evaluate the efficacy and safety of NSAIDs in patients with active AS. A total of 9 randomized controlled trials focusing on 6 NSAIDs, including etoricoxib, celecoxib, meloxicam, diclofenac, naproxen and beta-D-mannuronic acid (M2000), were analyzed in the present study. The efficacy endpoints included total pain score, patients' global assessment of disease activity (PGA), Bath Ankylosing Spondylitis Functional Index (BASFI) and the rate of achieving an Assessment in Ankylosing Spondylitis 20% response (ASAS20). The safety endpoints included total adverse events (AEs), gastrointestinal (GI) AEs, withdrawals due to AEs and serious AEs. NSAIDs were compared with the placebo and among themselves using Bayesian network meta-analysis, calculating mean differences (MDs) for continuous data and odds ratios for dichotomous data. The analysis revealed that all NSAIDs were significantly more effective in reducing pain severity than placebo (MDs between -17.49 and -25.99). Similarly, significant improvements in PGA, BASFI and ASAS20 were determined in patients receiving NSAIDs. Furthermore, etoricoxib was ranked as the most efficacious treatment for patients with AS. With regard to safety, there were no significant differences between NSAIDs and placebo in terms of total AEs, withdrawals due to AEs or serious AEs. Furthermore, no significant differences in AEs were identified between M2000 and the placebo. However, patients treated with diclofenac and naproxen had a higher risk of GI events than those taking placebo. In conclusion, the NSAIDs were all highly effective and well-tolerated in the treatment of AS. However, clinicians should take GI toxicity into account when prescribing NSAIDs.

Efficacy and safety of a supplement combination for hand osteoarthritis pain: protocol for an internet-based randomised placebo-controlled trial (The RADIANT study)

IntroductionHand osteoarthritis (HOA) is a highly prevalent disabling joint disease. The current management regimens are limited. Potentially as a consequence, many people turn to complementary and alternative medicines for symptomatic...

Impact of discordance between patient's and evaluator's global assessment on treatment outcomes in 14868 patients with spondyloarthritis.

To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe. Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients. We included 14868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P<0.001), with 6/12/24-months' BASDAI < 2 (P≤0.002) and ASDAS < 1.3 (P≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P≤0.04) and DAPSA28 ≤ 4 (P≤0.01), but not DAS28CRP(3)<2.6 (P≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients. High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.

Trial of Anifrolumab in Active Systemic Lupus Erythematosus

BackgroundAnifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point.MethodsWe randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate.ResultsA total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P=0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group.ConclusionsMonthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.)

Validation of prediction models of severe disease course and non-achievement of remission in juvenile idiopathic arthritis part 2: results of the Nordic model in the Canadian cohort

BackgroundValidated clinical prediction models to identify children with poor prognosis at the time of juvenile idiopathic arthritis (JIA) diagnosis would be very helpful for tailoring treatments, and avoiding under- or over-treatment. Our objective was to externally validate Nordic clinical prediction models in Canadian patients with JIA.MethodsWe used data from 513 subjects at the 3-year follow-up from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcomes were non-achievement of remission, severe disease course, and functional disability. The Nordic models were evaluated exactly as published and after fine-tuning the logistic regression coefficients using multiple data splits of the Canadian cohort. Missing data was handled with multiple imputation, and prediction ability was assessed with C-indices. C-index values > 0.7 were deemed to reflect helpful prediction.ResultsOverall, 81% of evaluable patients did not achieve remission off medications, 15% experienced a severe disease course, and 38% reported disability (CHAQ score > 0). The Nordic model for predicting non-achievement of remission had a C-index of 0.68 (95% CI 0.62–0.74), and 0.74 (0.67–0.80) after fine-tuning. For prediction of severe disease course, it had a C-index of 0.69 (0.61–0.78), and 0.79 (0.68–0.91) after fine-tuning. The fine-tuned Nordic model identified 85% of the cohort as low risk for a severe disease course (< 20% chance) and 7% as high risk (> 60% chance). The Nordic model to predict functional disability had a C-index of 0.57 (0.50–0.63), and 0.51 (0.39–0.63) after fine-tuning.ConclusionsFine-tuned Nordic models, combining active joint count, physician global assessment of disease activity, morning stiffness, and ankle involvement, predicted well non-achievement of remission and severe disease course in Canadian patients with JIA. The Nordic model for predicting disability could not predict functional disability in Canadian patients.

Effectiveness and safety study of oral triamcinolone in patients with rheumatoid arthritis in India

INTRODUCTION: This study was conducted to assess the effectiveness and safety of low-dose oral triamcinolone (Kenacort®, Abbott Healthcare Pvt. Ltd) in combination with disease-modifying antirheumatic drugs (DMARDs) in Indian patients with rheumatoid arthritis (RA).MATERIALS AND METHODS: Patients with an established diagnosis of RA, on a stable dose of DMARDs for at least 6-weeks, with evidence of disease flare-up or insufficient response to DMARDs were enrolled. Effectiveness of triamcinolone (4 mg) on disease activity (Disease Activity Score-28 [DAS28]), severity (Visual Analog Scale) and duration of morning stiffness, tender joint count (TJC), swollen joint count (SJC), patient global assessment of disease activity (Health Assessment Questionnaire-Disability Index [HAQ-DI]), quality of life (RAND 36-Item Health Survey score [SF-36]), and safety at 6 and 12 weeks of treatment were assessed.RESULTS: About 98.3% of patients completed the study (119/121; female: 64.5%). A significant improvement in DAS28 score was evident at weeks 6 and 12 compared to baseline (baseline: mean [standard deviation (SD)]: 6.6 (0.9); week 6: mean (SD): 5.5 (0.9); 95% confidence interval difference (CI): −1.3 to −1.0; P < 0.001; week 12: mean [SD]:4.7 [0.7]; 95% CI difference: −2.1 to −1.8; P < 0.001). Severity and duration of morning stiffness also improved significantly at the end of 6 and 12 weeks of treatment (P < 0.001). Substantial improvement in TJC, SJC, HAQ-DI score, and RAND 36-Item score was also evident (P < 0.001). Commonly reported adverse events were gastroesophageal reflux disease (3.3%), headache (3.3%), and fever (2.5%), which were mild and resolved subsequently.CONCLUSION: Low-dose triamcinolone with DMARDs was effective and well-tolerated in Indian patients with RA and in those with evidence of disease flare-up or insufficient response to DMARDs.

Multicenter, Open-Label, Long-term Extension to Describe the Safety of Tocilizumab in Patients with Early, Moderate to Severe Rheumatoid Arthritis

Introduction: Biologic DMARDs (Disease Modifying Anti Rheumatic Drugs) have shown to be effective in the treatment of rheumatoid arthritis (RA) resistant to the use of synthetic DMARDs. The primary goal of this study was to assess the long-term safety of the use of tocilizumab in patients with early rheumatoid arthritis, moderate to severe disease activity. The secondary goal was to assess the efficiency of tocilizumab in achieving and maintaining clinical remission of the disease. Methods: ML28133 is a long-term, extended study of 13 patients with rheumatoid arthritis treated with tocilizumab. Two patients were male (15.4%), 11 (84.61%) female. The average age of patients was 53.27+/-10.68. Patients received 8 mg/kg tocilizumab i.v. every four weeks, 104 weeks overall. Safety was assessed following side effects, blood tests, physical examination and vital signs. Efficiency was assessed by achieving and maintaining clinical remission according to DAS28 (Disease Activity Score 28), global assessment of disease activity, VAS score and HAQ-DI (Health Activity Score) questionnaire. Results: Incidence of side effects was 76.92%. Infections were of special interest and were most common (15.3%). Four patients had serious adverse events, three of which associated with tocilizumab, and therapy was stopped. In 11 (84.6%) of the 13 treated patients clinical remission was achieved at times. At the end of the study, 8 out of 9 patients were in remission. Conclusion: The results have shown significant therapeutic effect of tocilizumab even in the most severe forms of the disease, which gives hope for its use as a monotherapy.

Comparative characteristics of early psoriatic arthritis with and without axial skeleton injury (a subanalysis of the all-Russian registry of patients with psoriatic arthritis)

Objective: to compare the clinical features of two groups of patients with early psoriatic arthritis (PsA): with the involvement of the axial skeleton and without axial lesion. Subjects and methods . Examinations were made in 95 patients (47 men and 48 women) with early PsA from the Russian registry, the diagnosis met the CASPAR criteria; their mean age was 36.5+10.7 years; the duration of arthritis was 12.1 + 10.3 months. In addition to the standard examination, all the patients underwent evaluation of inflammatory back pain (IBP) (ASAS criteria), pelvic radiography, and determination of HLA-B27; 79 patients had additionally magnetic resonance imaging (MRI) of the sacroiliac joints (SIJ). Active sacroiliitis (SI) detected on MRI (MRI-SI) was identified as bone marrow edema (osteitis) in the STIR mode. Radiographic SI on (rSI) was recorded if there were bilateral or unilateral changes (Kellgren grades >II or >III, respectively). The results of radiography and MRI were assessed by an independent radiologist. The disease activity in patients with IBP was evaluated by BASDAI. patients’ global assessment of disease activity (GADA) and assessment of pain intensity (PI) were made using a 100 mm visual analogue scale (VAS). The patients were divided into two groups: 1) those with axial lesion (axPsA), who had IBP, and/or rSI, and/or MRI-SI; 2) those without axial lesion, who had only peripheral PsA (pPsA). Results and discussion . IBP was found in 63 (66.3%) patients; it was transient, episodic in 35 (60.3%) from them. MRI-SI was detected in 28 (35.4%) from the 79 patients; rSI — in 29 (30.5%). The axPsA group included 65 (68.4%) patients and the pPsA group consisted of 30 (31.6%) patients. There was a preponderance of males in the axPsA group (60%) and that of females in the pPsA group (73.3%) ( р =0.003). The patients with axPsA were younger than those with pPsA (33.9+9.6 and 41.7+10.6 years, respectively; p=0.0007). They were more frequently HLA-B27 positive than pPSA patients: 47.6% (n=30) and 23.3% (n=7) (p=0.02); and had shorter duration of arthritis: 10.3+8.7 and 16.1 + 11.7 months, respectively (p = 0.008). In the axPsA group, of PI was worse than that in the pPsA group: GADA averaged 58.4+17.3 and 49.8+16.7 mm (p=0.02); PI >50 mm was observed in 44 (67.7%) and 13 (43.3%) patients, respectively [odds ratio (OR), 2.74; 95% confidence interval (CI), 1.13-6.67; p=0.026]. More severe skin lesions were seen in patients with axPsA than in those with pPsA: BSA >3% was detected in 24 (40.7%) and 4 (14.8%) patients (OR, 3.94; 95% CI, 1.21-12.86; p=0.023); the median PASI was 9.7 [6.6; 21.5] and 5.0 [0.0; 6.4] respectively (p=0.005). The patients with axPsA showed higher C-reactive protein (CRP) values than those with pPsA: CRP >5 mg/L was found in 58 (89.3%) and 19 (63.3%) patients, respectively (OR, 4.80; 95% CI, 1.63-14.13; p=0.004). Conclusion. The targeted examination of PsA patients revealed axial lesion in 68% from them; delayed diagnosis was generally associated with the inconsistent character of IBP. Among the patients with axPsA, there are significantly more males, younger adults, and HLA-B27 carriers. With the involvement of the axial skeleton, there was a more severe course of the disease: worse PI, a greater severity of skin lesions, and higher CRP levels. Considering the need for early diagnosis of axPsA for the timely use of biological agents, studies of this problem should be continued using large patient cohorts.

Factors associated with and cutoff points for Patient Acceptable Symptom State (PASS) in rheumatoid arthritis.

To identify factors associated with and cutoff points for patients' acceptance of symptom state in Thai patients with rheumatoid arthritis (RA). Patients aged ≥ 18years diagnosed with RA who were followed-up at the outpatient rheumatology clinics of Siriraj Hospital and Phramongkutklao Hospital during May 2017 to May 2019 responded to the Patient Acceptable Symptom State (PASS) questionnaire. The PASS questionnaire comprises three questions, including current PASS, future PASS (3months), and lifelong PASS. Univariate (p < 0.2) and multivariate (p < 0.05) analyses were performed to identify factors significantly associated with PASS. Cutoff points of indices related to disease activity, functional status, and health-related quality of life (HRQoL) in patients with PASS were identified using the 75th percentile and receiver operating characteristic curve analysis based on optimal sensitivity and specificity. From the 443 enrolled patients, 85%, 80%, and 84% considered themselves to be in current, future, and lifelong PASS, respectively. Step-wise backward multivariate analysis revealed disease duration, disease activity, functional status, cardiovascular comorbidities, and HRQoL to be independently associated with PASS. PASS cutoff points were identified, as follows: Disease Activity Score 28, 3.40-3.52; Health Assessment Questionnaire, 0.69-1; Patient Global Assessment of Disease Activity, 2.5-3; Physician Global Assessment of Disease Activity, 1-1.5; and EuroQoL-5 Dimensions, 0.83-0.86. PASS was high in Thai patients with RA. Patients accepted their disease state at moderate disease activity and mild functional impairment. More shared decision-making and patient education should be incorporated into daily practice to improve patient outcomes.Key Points•Patients with RA accepted their disease state at moderate disease activity and mild functional impairment, while a "treat-to-target" strategy aiming at remission or low disease activity is recommended as a standard goal.•More shared decision-making and patient education should be incorporated into daily practice to improve outcomes.

Longitudinal Occurrence and Predictors of Patient-Provider Discordance Between Global Assessments of Disease Activity in Rheumatoid Arthritis: A Case-Control Study.

To identify longitudinal predictors of discordance between patients with rheumatoid arthritis (RA) and their health care providers, where patient global assessment of disease activity is substantially higher than provider global assessment. This retrospective case-control study included 102 cases with positive discordance (i.e., ≥25 mm between patient and provider global assessments) and 102 controls without discordance who were matched for age, sex, RA duration, and Clinical Disease Activity Index (CDAI) score. Data were collected at the baseline visit (date of diagnosis or earliest available visit), the index visit (participation in a previous cross-sectional study), and at up to 11 additional visits before the index visit. Data included patient characteristics, disease activity measures, Disease Activity Score in 28 joints (3-variable) using the C-reactive protein level (DAS28-CRP), and medications. Data were analyzed by using linear and logistic regression models with smoothing splines for nonlinear trends. Overall, the mean age was 63 years, 75% of patients were female, and the mean RA duration was 10 years. Compared with controls, cases had higher rates of discordant visits during the 4 years before the index visit, and they had a higher CDAI score and DAS28-CRP earlier in the disease course. Cases more frequently had antinuclear antibodies, nonerosive disease, prior depression, or prior use of antidepressants or fibromyalgia medications. Disease-modifying medication use was not different between cases and controls. The findings inform new hypotheses about the relationships of disease activity and antinuclear antibodies to the later occurrence of positive discordance among patients with RA.

Effects of upadacitinib on patient-reported outcomes: results from SELECT-BEYOND, a phase 3 randomized trial in patients with rheumatoid arthritis and inadequate responses to biologic disease-modifying antirheumatic drugs

BackgroundPatient-reported outcomes (PROs) are important when evaluating treatment benefits in rheumatoid arthritis (RA). We compared upadacitinib, an oral, selective JAK-1 inhibitor, with placebo to assess clinically meaningful improvements in PROs in patients with RA who have had inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARD-IR).MethodsPRO responses between upadacitinib 15 mg or 30 mg and placebo were evaluated at week 12 from the SELECT-BEYOND trial. Improvement was determined by measuring Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36), duration and severity of morning (AM) stiffness, and Insomnia Severity Index (ISI). Least squares mean changes and percentage of patients reporting improvements ≥ minimum clinically important differences (MCID) and scores greater than or equal to normative values were determined. The number needed to treat (NNT) to achieve clinically meaningful improvements was calculated.ResultsIn 498 patients, both upadacitinib doses resulted in statistically significant changes from baseline versus placebo in PtGA, pain, HAQ-DI, SF-36 Physical Component Summary (PCS), 7 of 8 SF-36 domains (15 mg), 6 of 8 SF-36 domains (30 mg), and AM stiffness duration and severity. Compared with placebo, more upadacitinib-treated patients reported improvements ≥ MCID in PtGA, pain, HAQ-DI, SF-36 PCS, 7 of 8 SF-36 domains (15 mg), 5 of 8 SF-36 domains (30 mg), AM stiffness duration and severity, and ISI (30 mg) and scores ≥ normative values in HAQ-DI and SF-36 domains. Across most PROs, NNTs to achieve MCID with upadacitinib ranged from 4 to 7 patients.ConclusionsIn bDMARD-IR RA patients, upadacitinib (15 mg or 30 mg) improved multiple aspects of quality of life, and more patients reached clinically meaningful improvements approaching normative values compared with placebo.Trial registrationThe trial is registered with ClinicalTrials.gov (NCT02706847), registered 6 March 2016.

Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT

BackgroundTo evaluate the effect of upadacitinib on patient-reported outcomes (PROs) in patients with RA who had an inadequate response to csDMARDs.MethodsPatients in SELECT-NEXT, a randomised controlled trial, were on a background of csDMARDs and received upadacitinib 15 mg and 30 mg or placebo daily for 12 weeks. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), duration and severity of morning (AM) joint stiffness, Short Form 36 Health Survey (SF-36), and Work Instability Scale for RA (RA-WIS). Least squares mean (LSM) changes were based on mixed-effect repeated measure models. Percentages of patients reporting improvements ≥ minimum clinically important differences (MCIDs) and scores ≥ normative values and number needed to treat (NNT) were determined; group comparisons used chi-square tests.ResultsData from 661 patients were analysed. Compared with placebo, patients receiving upadacitinib reported statistically significant improvements (both doses, P < 0.05) in PtGA, pain, HAQ-DI, FACIT-F, duration and severity of AM stiffness, SF-36 (PCS and 6/8 domains), and RA-WIS at week 12. Significantly, more upadacitinib-treated patients (both doses, P < 0.05) reported improvements ≥ MCID in PtGA, pain, HAQ-DI, FACIT-F, AM stiffness, SF-36 (PCS and 4 or 7/8 domains), and RA-WIS and scores ≥ normative values in HAQ-DI, FACIT-F, and SF-36 (PCS and 4 or 5/8 domains). For most PROs, the incremental NNT with upadacitinib to report clinically meaningful improvement from baseline ranged from 4 to 8 patients.ConclusionsUpadacitinib 15 mg or 30 mg daily for 12 weeks resulted in significant and clinically meaningful improvements in global disease activity, pain, physical function, fatigue, duration and severity of AM stiffness, HRQOL, and work instability among csDMARD-IR patients with RA.Trial registrationClinicaltrials.gov, NCT02675426. Retrospectively registered 5 February 2016.

Patient-Reported Outcomes in Adult Idiopathic Inflammatory Myopathies.

Idiopathic inflammatory myopathies (IIM) have considerable impact on patient symptoms and quality of life. We have reviewed the evolution of patient-centered care and use of patient-reported outcome measures (PROMs) for adults with IIM. Use of PROMs in myositis care and research is limited, although the importance of incorporation into routine practice and trials has become increasingly recognized. Several key domains/measures have been identified including the patient global assessment of disease activity, physical function as measured by the health assessment questionnaire-disability index (HAQ-DI), Short Form Health Survey-36 (SF-36), or the Patient-Reported Outcome Measurement Information System ® (PROMIS®) in adult IIM. Data are limited for these instruments concerning their reliability, content and construct validity, and responsiveness. Incorporation of the patient perspective into clinical care and research may be used to address the unmet/unaddressed needs of the patient living with myositis. Several ongoing projects aim to bring validated PROMs to the IIM community.

Exercise programmes for ankylosing spondylitis.

Exercise programmes for ankylosing spondylitis.

Patient-reported outcomes for tofacitinib with and without methotrexate, or adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial

ObjectiveTo provide the first direct comparison of patient-reported outcomes (PROs) following treatment with tofacitinib monotherapy versus tofacitinib or adalimumab (ADA) in combination with methotrexate (MTX) in patients with rheumatoid arthritis...

Assessing the multimorbid profile (CIRS) in rheumatoid arthritis. First results

Objective : to assess the presence and nature of multimorbidity in patients with rheumatoid arthritis (RA) and the impact of multimorbidity on disease activity. Patients and methods . The investigation enrolled 117 patients (mean age, 54.8+14.8years) with RA according to the 2010 ACR/EULAR criteria, who had been examined and treated at the V.A. Nasonova Research Institute of Rheumatology in 2018—2019. The median disease duration was 5.0 [1.5; 9.5] years; the mean DAS28 score was 5.0+1.3. Documentation and anamnesis data were analyzed with emphasis on associated diseases. The Cumulative Illness Rating Scale (CIRS) was used to assess the profile of multimorbidity. Results and discussion . The patients with RA had a high index of the spectrum of multimorbidity; comorbidity was detected in 96 (82%) cases. The median number of diseases in one patient was 2 [1; 4], the mean total CIRS score was 6.7+3.3; the median value was 2.5 [1; 6]. The number of comorbidities diagnosed before using the CIRS was significantly fewer (by 48%; p<0.01) than was found in the investigation conducted. Chronic kidney disease that occurred in almost half (42.5%) of cases was most commonly undiagnosed in the cohort under study; on average, every three patients were not found to have signs of metabolic syndrome (hyperglycemia in 29% and obesity in 13.5%) and chronic hypoxia (new-onset anemia verified in 24% of cases). There was a correlation of the quantitative equivalent of multimorbidity with the clinical and laboratory measures of RA activity, including the number of painful joints (r = 0.39; p<0.001), overall patient assessment (r=0.37; p=0.03), physician's global assessment of disease activity (r = 0.37; p < 0.01), DAS28 (r = 0.42; p<0.001), CDAI (r=0.37; p<0.001), SDAI (r=0.34; p< 0.001), HAQ (r=0.34;p<0.001). The total CIRSscore did not differ in patients with early- and advanced- or end-stage RA: 6.6+3.5 and 6.7+3.3, respectively (p=0.9). Conclusion . A systematic screening of multimorbidity should be carried out in all patients with RA. It is advisable to use the CIRS to estimate the prevalence of multimorbidity and its consequences.

Inter-observer agreement of standard joint count examination and disease global assessment in a cohort of Egyptian Rheumatoid Arthritis patients

ObjectivesTo assess the inter-observer agreement of standard joint count between experienced Rheumatology professor (Prof) and young Rheumatology fellow (candidate), and to compare disease global assessment between professor, young candidate and patients. MethodsThis study included one hundred rheumatoid arthritis patients. For all patients independent clinical evaluation was done by two rheumatologists (professor and candidate) for detection of tenderness in 28 joints and swelling in 26 joints. The study also involved global assessment of disease activity by the provider (Prof and candidate) (EGA) as well as by the patient (PGA). The EGA was determined without previous knowledge of the patient's laboratory test results. ResultsA highly significant accordance (correlation) between professor and candidate was found in both the number of tender joints (p<0.001) (r=0.946), and the number of swollen joints (p<0.001) (r=0.797). Regarding swollen joints, the highest agreement was in right knee (0.929), while poor agreement was found in the right 5th MCP (0.049). Regarding tender joints, the highest analogy was in the right elbow (0.899), in contrast to the left 3rd PIP (0.462) which showed the least congruence. Agreement study using kappa measurement for disease global assessment showed: moderate agreement (between professor and candidate) (0.405), fair agreement between (professor and patient) (0.213), fair agreement between (candidate and patient) (0.367). ConclusionInter-observer reliability was better for TJCs than SJCs. Regarding SJCs agreement was better in large joints such as the knees compared to the small joints such as the MCPs. Disease global assessment may show discrepancy between patients and physicians.

The pain trajectory of juvenile idiopathic arthritis (JIA): translating from adolescent patient report to behavioural sensitivity in a juvenile animal model

BackgroundWhile pain is a common symptom in JIA patients, it remains unclear why some JIA patients develop ongoing or persistent pain. Complex clinical and social settings confound analysis of individual factors that may contribute to this pain. To address this, we first undertook a retrospective analysis of pain reports in a JIA patient cohort with the aim of identifying potential factors contributing to persistent pain. We then carried out an experimental laboratory study, using joint inflammatory pain behaviour in rodents, to validate the role of these factors in the onset of persistent pain under controlled conditions.MethodsPatients: Retrospective analysis of anonymised pain visual analogue scale (VAS) scores and accompanying clinical scores from 97 JIA patients aged 13–19 (mean: 16.40 ± 1.21) collected over 50 weeks. Rats: Experimental study of pain behaviour following intra-articular microinjection of complete Freund’s adjuvant (CFA) in adolescents (n = 25) and young adults (n = 43). Some animals (n = 21) had been previously exposed to joint inflammation in infancy or adolescence.ResultsPatients: Cluster analysis of patient pain VAS scores revealed three trajectories over 50 weeks: consistently low pain (n = 45), variable pain (n = 30) and persistently high pain (n = 22). Number of actively inflamed joints did not differ in the three groups. High pain at a single visit correlated with greater physician global assessment of disease activity, while a high pain trajectory over 50 weeks was associated with more limited joints but fewer actively inflamed joints. Rats: Rodents administered ankle joint CFA also exhibit low, medium and high joint pain sensitivities, independent of joint inflammation. Prolonged inflammatory pain behaviour was associated with high background pain sensitivity, following joint inflammation at an earlier stage in life.ConclusionsBoth JIA patients and rodents differ in their individual pain sensitivity independent of the concurrent joint inflammation. Using experimental animal models allows us to isolate physiological factors underlying these differences, independently of social or clinical factors. The results suggest that a history of prior arthritic activity/joint inflammation may contribute to high pain sensitivity in adolescents with JIA.