Change In Health Assessment Questionnaire Research Articles

Changes in Physical Function using Three Methods of Scoring the Health Assessment Questionnaire in Established Active Rheumatoid Arthritis

Background: We investigated sensitivity to change of three scoring methods of the Health Assessment Questionnaire (HAQ) in relation to change in disease activity in patients with active rheumatoid arthritis (RA). Patients and Methods: Adult RA-patients with complete data in the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology database with respect to the 20 HAQ questions and disease activity score with 28-joint count using the erythrocyte sedimentation rate (DAS28-ESR) for 2 visits, at least 6–12 months apart, and high disease activity (DAS28-ESR >5.1) at visit 1. Changes in HAQ scored by the (1) conventional method (HAQ-8), (2) HAQ-Tomlin method (HAQ-T), and (3) HAQ-20-item method (HAQ-20) were analyzed in relation to the European League Against Rheumatism (EULAR) RA response criteria, dichotomized to good/moderate and no response. Results: In 421 patients, mean standard deviation (SD) DAS28-ESR declined significantly (6.1 [0.8]–4.8 [1.6], P < 0.0001), over a mean period (SD) of 8.7 (1.9) months. Median HAQ scores improved by all three scoring methods, HAQ-8 (1.6–1.4); HAQ-T (1.2–0.7); and HAQ-20 (1.2–0.9) with similar effect sizes of 0.97, 0.96, and 0.95, respectively. The proportion who achieved a HAQ minimally clinically important improvement (MCII) of ≥0.22 was significantly higher in 47% of patients with EULAR good/moderate score compared to the no response patients (64% vs. 11%, P < 0.0001). Good/moderate EULAR response, higher baseline DAS28, and higher baseline HAQ (7.11, 1.55, and 1.06, respectively) were independent predictors of achieving a HAQ-MCII. Conclusion: Three HAQ scoring methods performed similarly in sensitivity to change with no advantage of alternative scoring methods compared to the conventional HAQ-8 method. A good/moderate EULAR response, despite long disease duration, was associated with a significant likelihood of achieving a HAQ-MCII.

OA14b Etanercept originator versus its biosimilar (SB4) for the treatment of rheumatoid arthritis. Are they truly similar?

Abstract Background/Aims Etanercept biosimilar SB4 (ETN-B) showed comparable efficacy to its biologic originator (ETN-O) among biologic-naïve patients with rheumatoid arthritis (RA) in randomised controlled trials. Subsequently, a nationwide guideline in the United Kingdom (UK) obligated the prescription of biosimilars in 2016, resulting in significant cost-savings to the NHS. However, real-world evidence comparing ETN-O and ETN-B is limited. This analysis aims to compare the effectiveness of ETN-O versus ETN-B amongst biologic-naïve patients with RA treated in routine clinical practice in the UK. Methods The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included patients starting their first biologic (ETN-O or ETN-B), recruited since 2010, with at least one follow-up. Baseline data are collected at start of therapy, including patient demographics and disease activity. Follow-up data are collected six monthly for the first three years and annually thereafter, including changes in disease activity and anti-rheumatic therapy. Key outcomes assessed were change in Disease Activity Score for 28-joints (DAS28), DAS28 remission, EULAR treatment response, change in Health Assessment Questionnaire (HAQ), and minimal clinically important difference (MCID) in HAQ. Drug retention was explored using Kaplan-Meier and Cox-regression analyses, along with reasons for treatment withdrawal. Multiple imputation was used to account for missing data and confounding by indication was accounted for using propensity-decile adjustment. Results This analysis included 1927 patients with RA starting their first biologic therapy: 996 (52%) ETN-O and 931 (48%) ETN-B. At six-months, change in DAS28 and HAQ were similar between therapies (Table). There were no differences in key imputed propensity adjusted outcomes (odds ratio [95% confidence interval]): DAS28 remission: 0.90 (0.7-1.1, p = 0.3); MCID in HAQ: 0.86 (0.7-1.1, p = 0.3) and EULAR treatment response: 0.96 (0.8-1.2, p = 0.8). One-year retention rates were 69% (95% CI: 66-72) for ETN-O and 70% (95% CI: 67-73) for ETN-B and the main reasons for treatment withdrawal were adverse events and ineffectiveness for both drugs. Conclusion This analysis is the first to our knowledge to show similar outcomes amongst biologic-naïve patients with RA treated with either ETN-O or ETN-B using real-world data, which brings further evidence for similarity between the drugs. Disclosure A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

Disease Activity Indices in Rheumatoid Arthritis: Comparative Performance to Detect Changes in Function, IL-6 Levels, and Radiographic Progression.

Objective: To compare the capacity of various disease activity indices to evaluate changes in function, IL-6 levels, and radiographic progression in early and established rheumatoid arthritis (RA).Methods: Secondary data analysis of a clinical trial assessing the efficacy of tocilizumab in patients with established RA (ACT-RAY) and a longitudinal prospective register of early arthritis (PEARL). Targeted outcomes were changes in physical function, measured with the health assessment questionnaire (HAQ), IL-6 serum levels, and radiographic progression. The “Hospital Universitario La Princesa Index” (HUPI), DAS28 using erythrocyte sedimentation rate and SDAI were the disease activity indices compared. Models adjusted for age and sex were fitted for each outcome and index and ranked based on the R2 parameter and the quasi-likelihood under the independence model criterion.Results: Data from 8,090 visits (550 patients) from ACT-RAY and 775 visits (534 patients) from PEARL were analyzed. The best performing models for HAQ were the HUPI (R2 = 0.351) and SDAI ones (R2 = 0.329). For serum IL-6 levels, the SDAI (R2 = 0.208) followed by the HUPI model (R2 = 0.205). For radiographic progression in ACT-RAY, the HUPI (R2 = 0.034) and the DAS28 models (R2 = 0.026) performed best whereas the DAS28 (R2 = 0.030) and HUPI models (R2 = 0.023) did so in PEARL.Conclusions: HUPI outperformed other indices identifying changes in HAQ and radiographic progression and performed similarly to SDAI for IL-6 serum levels.

Effectiveness and safety of iguratimod treatment in patients with active rheumatoid arthritis in Chinese: A nationwide, prospective real-world study

BackgroundThere is heterogeneity in the clinical manifestations and responses to drugs in RA patients due to variety of factors such as genes and environment. Despite advances in the treatment of rheumatoid arthritis (RA), approximately 40% of RA patients still do not achieve primary clinical outcomes in randomized trials, and its low remission rate and high economic consumption remain unresolved, especially in developing countries. Iguratimod (IGU) is a new disease-modifying anti-rheumatic drug (DMARD) with a low price that has demonstrated good efficacy and safety in clinical trials and was approved for active RA in China and Japan. As the most populous country in the Western Pacific region, it is warranted to conduct a study with a large scale of patients in a real-life setting. Our study confirms the new option for RA patients, which is potentially benificial for public health in developing countries. MethodsThis was a nationwide, prospective real-world study of IGU. Eligible subjects were active adult RA patients who aged 18 to 85 with or without multiple comorbidities such as hypertension and diabetes with DMARDs at a stable dosage for at least 12 weeks, or without ongoing DMARDs. A two-stage design was used for this study. In the first stage (the first 12 weeks), IGU 25 mg bid was added as monotherapy or to the background therapy, and in the second stage (the latter 12 weeks), adjustment of RA medicines other than IGU was allowed according to the participants’ disease activity. The primary endpoints were American College of Rheumatology 20% response (ACR20) 24 weeks and adverse events during 24 weeks. The secondary endpoints were ACR50 and ACR70 over 24 weeks, the changes of DAS28 and Health Assessment Questionnaire (HAQ) at week 12 and week 24 from baseline. The trial was registered with ClinicalTrials.gov, number NCT01554917. FindingsBetween March 2012 and January 2015, 1759 participants were enrolled, of whom 81•5% (1433/1759) completed the study. Notably, 1597 patients in the full analysis set were assessed for the effectiveness and 1751 patients were in the safety analysis set; 71•9% (1148/1597) of the patients achieved the primary endpoint of ACR20 response at week 24, and 51•7% (906/1751) patients had at least 1 adverse event (AE). The incidence of the clinical significant AE (grade≥3) of special interest was 3•4% (54 patients for grade 3 and 6 patients for grade 4), and 0•7% (13/1751) of patients developed SAEs associated with IGU. The most common clinical significant AEs were infection in 0•6% (10/1751) of the patients, abdominal discomfort in 0•5% (9/1751) of the patients including 0•2% (3/1751) gastric ulcer, fracture in 0•4% (7/1751), and increased alanine aminotransferase (ALT) in 0•2% (3/1751) of the patients. The secondary endpoint of ACR50 and ACR70 response rates at week 24 were 47•4% (757/1597) and 24•0% (384/1597). DAS28 was 4•11±1•27 and 3•75±1•32 at week 12 and 24, which was significantly decreased -1•40±1•10 and -1•75±1•26 compared with baseline (P<0•001) respectively. Changes in HAQ at week 12 and 24 from baseline were -7•4 ± 9•18 and -8•5 ± 9•97, respectively (all P<0•001). Stratified analysis results showed that the patients with shorter disease duration, male gender had better response to IGU. There was no significant difference in ACR20/50/70 responses between elderly patients(≥65 years) and younger patients(<65 years), IGU monotherapy or combined with other DMARDs. However, more fractures (1•1% vs 0•5%; P = 0•64) and infections (8•7% vs 7•9%; P = 0•69) were observed in elderly patients in our study. InterpretationOur results confirmed the effectiveness and safety of IGU as a new DMARD for active patients with RA as monotherapy or combination therapy. FundingThis study was supported by “the 11th Five-Year-Plan for Science and Technology Support Program (2012ZX09104-103-01)”.

Assessment of Treatment Safety and Quality of Life in Patients Receiving Etanercept Biosimilar for Autoimmune Arthritis (ASQA): A Multicenter Post-marketing Surveillance Study.

PhaseIV post-marketing surveillance studies are needed to evaluate the real-world safety and effectiveness of drug products. This study aimed to evaluate the safety and effectiveness of biosimilar etanercept (Altebrel, AryoGen Co., Iran) in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). In this open-label, multicenter, prospective, observational, post-marketing surveillance study, 583 patients received biosimilar etanercept 25mg twice weekly or 50mg once weekly and were followed up to 12months. The primary objective was to evaluate the safety of biosimilar etanercept by documenting all the adverse events in the case report forms throughout the study period. The secondary objective was to evaluate the effectiveness of biosimilar etanercept in study patients, where longitudinal changes in health assessment questionnaire (HAQ), pain, and disease activity scores were assessed. A total of 583 patients (44.80 ± 13.09years of age) were included and followed for an average of 8.12 ± 3.96months. Among all patients, 172 (29.50%) experienced at least one adverse event, and injection site reaction, abdominal pain, and upper respiratory tract infection were the most common. HAQ scores decreased from 1.32 ± 0.77 at baseline to 0.81 ± 0.61 at 12months in patients with RA/PsA (p < 0.01) and from 0.82 ± 0.58 at baseline to 0.66 ± 0.63 at 12months in patients with AS (p = 0.18). Pain scores decreased from 6.49 ± 2.41 at baseline to 3.51 ± 2.39 at 12months (p < 0.01). The results demonstrated the real-world safety and effectiveness of biosimilar etanercept in patients with RA, PsA, and AS. ClinicalTrials.gov identifier NCT04582084.

Evaluation of the Effect of Diabetes on Rheumatoid Arthritis-related Outcomes in an Electronic Health Record-based Rheumatology Registry.

Patients with rheumatoid arthritis (RA) who also have diabetes mellitus (DM) might have worse clinical outcomes and adverse events compared to patients with RA who do not have DM. We evaluated the effects of DM on Health Assessment Questionnaire (HAQ) changes and outpatient infection rates in patients with RA. Using the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) electronic health record-based registry, we identified patients with RA who had ≥ 1 rheumatologist visit with a HAQ measured in 2016 (index visit), ≥ 1 previous visit, and a subsequent outcome visit with the same HAQ measured at 12 months (± 3 months). We identified DM by diagnosis codes, medications, or laboratory values. Outpatient infection was defined by diagnosis codes or antiinfective medications. We calculated mean HAQ change and incidence rate (IR) of outpatient infections among patients with and without DM. Generalized linear models and Cox regression were used to calculate the adjusted mean HAQ change and HRs. We identified 3853 RA patients with DM and 18,487 without DM. The mean HAQ change between index and outcome visit among patients with DM was 0.03 and without DM was 0.002 (P < 0.01). We identified 761 outpatient infections for patients with DM with an IR of 22.6 (95% CI 21.0-24.2) per 100 person-years and 3239 among patients without DM with an IR of 19.8 (95% CI 19.1-20.5). The adjusted HR of outpatient infections among patients with DM was 0.99 (95% CI 0.91-1.07), compared to patients without DM. Patients with RA with concomitant DM had greater worsening, or less improvement, in their functional status, suggesting additional interventions may be needed for RA patients with DM to optimize treatment and management of other comorbidities.

The Impact of Frailty on Changes in Physical Function and Disease Activity Among Adults With Rheumatoid Arthritis.

ObjectiveReduced physical function and frailty are common in rheumatoid arthritis (RA). However, relationships between frailty and changes in physical function and disease activity over time in RA are unknown. We tested whether frailty is a risk factor for worsening patient‐reported physical function and disease activity in RA.MethodsAdults from a longitudinal RA cohort (N = 124) participated. By using an established frailty definition, individuals with three or more of the following deficits were considered frail: 1) body mass index less than or equal to 18.5, 2) low grip strength, 3) severe fatigue, 4) slow 4‐m walking speed, and 5) low physical activity. Individuals with one to two or zero deficits were considered “pre‐frail” or “robust,” respectively. Physical function and RA disease activity were assessed by the Health Assessment Questionnaire (HAQ) and Rheumatoid Arthritis Disease Activity Index (RADAI), respectively, at baseline and follow‐up 2 years later. Regression analyses modeled associations of frailty status with change in HAQ and RADAI scores between baseline and follow‐up with and without controlling for covariates. Associations of individual frailty components with change in HAQ and RADAI scores were also examined.ResultsAmong adults with RA, baseline frailty status predicted significant increases, or worsening, in HAQ (β: 0.4; 95% confidence interval: 0.1‐0.8; P < 0.01) but not RADAI scores (β: 0.5; 95% confidence interval: −0.4 to 1.5; P > 0.05) between baseline and follow‐up in fully adjusted models. Fatigue was an important contributor to this effect.ConclusionFrailty may be an important risk factor for reduced physical function over time in RA. Future studies should address whether interventions to reduce frailty improve physical function in RA.

Effect of Filgotinib vs Placebo on Clinical Response in Patients With Moderate to Severe Rheumatoid Arthritis Refractory to Disease-Modifying Antirheumatic Drug Therapy

Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options. To evaluate the effects of filgotinib vs placebo on the signs and symptoms of RA in a treatment-refractory population. A 24-week, randomized, placebo-controlled, multinational phase 3 trial conducted from July 2016 to June 2018 at 114 sites internationally, randomizing 449 adult patients (and treating 448) with moderately to severely active RA and inadequate response/intolerance to 1 or more prior bDMARDs. Filgotinib, 200 mg (n = 148); filgotinib, 100 mg (n = 153); or placebo (n = 148) once daily; patients continued concomitant stable conventional synthetic DMARDs (csDMARDs). The primary end point was the proportion of patients who achieved 20% improvement in the American College of Rheumatology criteria (ACR20) at week 12. Secondary outcomes included week 12 assessments of low disease activity (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] ≤3.2) and change in Health Assessment Questionnaire-Disability Index, 36-Item Short-Form Health Survey Physical Component, and Functional Assessment of Chronic Illness Therapy-Fatigue scores, as well as week 24 assessment of remission (DAS28-CRP <2.6) and adverse events. Among 448 patients who were treated (mean [SD] age, 56 [12] years; 360 women [80.4%]; mean [SD] DAS28-CRP score, 5.9 [0.96]; 105 [23.4%] with ≥3 prior bDMARDs), 381 (85%) completed the study. At week 12, more patients receiving filgotinib, 200 mg (66.0%) or 100 mg (57.5%), achieved ACR20 response (placebo, 31.1%; difference vs placebo: 34.9% [95% CI, 23.5%-46.3%] and 26.4% [95% CI, 15.0%-37.9%], respectively; both P < .001), including among patients with prior exposure to 3 or more bDMARDs (70.3%, 58.8%, and 17.6%, respectively; difference vs placebo: 52.6% [95% CI, 30.3%-75.0%] for filgotinib, 200 mg, and 41.2% [95% CI, 17.3%-65.0%] for filgotinib, 100 mg; both P < .001). The most common adverse events were nasopharyngitis (10.2%) for filgotinib, 200 mg; headache, nasopharyngitis, and upper respiratory infection (5.9% each) for filgotinib, 100 mg; and RA (6.1%) for placebo. Four uncomplicated herpes zoster cases and 1 retinal vein occlusion were reported with filgotinib; there were no opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations, or deaths. Among patients with active RA who had an inadequate response or intolerance to 1 or more bDMARDs, filgotinib, 100 mg daily or 200 mg daily, compared with placebo resulted in a significantly greater proportion achieving a clinical response at week 12. However, further research is needed to assess longer-term efficacy and safety. ClinicalTrials.gov Identifier: NCT02873936.

Impact of the combined presence of erosions and ACPA on rheumatoid arthritis disease activity over time: results from the METEOR registry

ObjectiveTo investigate associations between baseline presence of erosions and/or anti-citrullinated protein antibodies (ACPA) on functional ability, disease activity and treatment survival over time.MethodsReal life data from newly diagnosed rheumatoid arthritis...

Cost-Effectiveness of Secukinumab Versus Other Biologics in the Treatment of Psoriatic Arthritis: An Argentinean Perspective

ObjectivePsoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. This study assessed the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, versus other biologics in PsA from the Argentinean social security perspective. MethodsA semi-Markov model evaluated subcutaneous (sc) treatment with secukinumab 150 mg and 300 mg against other sc treatments such as adalimumab, certolizumab pegol, etanercept, golimumab, ustekinumab, and intravenous treatment infliximab in biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients over a lifetime horizon. Response to treatments was determined using the PsA Response Criteria (PsARC) at 12 weeks. Model inputs were derived from randomized controlled trials, network meta-analyses, published literature, and other Argentinean sources. Model outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios. Sensitivity analyses and alternative scenarios with a higher cost option were also conducted. ResultsAmong biologic-naïve PsA patients without psoriasis, secukinumab 150 mg provided the highest QALYs (7.18) versus all sc biologics at the lowest cost ($3 755 678 Argentine peso), thus dominating them. Among biologic-naïve PsA patients with psoriasis and biologic-experienced PsA patients, secukinumab 300 mg provided highest QALYs (6.99 and 7.53, respectively), dominated infliximab, and was cost-effective versus other sc biologics. Deterministic sensitivity analyses indicated sensitivity of results to variation in PsARC rates, drug acquisition costs, Health Assessment Questionnaire change, and utilities. A probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from an alternative scenario analysis were similar to base-case analysis. ConclusionsFor both biologic-naïve and experienced PsA patients, secukinumab is either a dominant or cost-effective treatment option compared with other biologics in Argentina.

Sarilumab monotherapy compared with adalimumab monotherapy for the treatment of moderately to severely active rheumatoid arthritis: an analysis of incremental cost per effectively treated patient.

PurposeTreatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment.Patients and methodsShort-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire – Disability Index score and via published algorithms.ResultsFor sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses.ConclusionSarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses.

Changes over Time and Responsiveness of the Cochin Hand Function Scale and Mouth Handicap in Systemic Sclerosis Scale in Patients with Systemic Sclerosis: A Prospective Observational Study.

To assess changes over time and responsiveness of the Cochin Hand Function Scale (CHFS) and Mouth Handicap In Systemic Sclerosis (MHISS) scale in patients with systemic sclerosis (SSc). This was a prospective longitudinal study. Participants were drawn from a convenience sample of individuals with SSc, who were attending the annual Congress of the Association des Sclérodermiques de France, the French SSc patients' association. Participants were evaluated twice by the CHFS, MHISS scale, Health Assessment Questionnaire, McMaster-Toronto Arthritis Patient Preference Disability Questionnaire, and other outcome measures. Differences in measures over time were evaluated using the Wilcoxon signed rank test. Responsiveness was assessed by the effect size and standardized response mean. Nonparametric Spearman rank correlation (r) was used to assess correlation between outcome measures. Forty-nine patients were assessed. The CHFS and MHISS scores worsened over time (mean [SD] differences 2.7 [10.7], P = 0.08, and 3.5 [9.8], P = 0.14, respectively). The CHFS effect size and standardized response mean values were -0.16 and -0.24, respectively, and MHISS values were -0.53 and -0.52, respectively. The correlation between change in the CHFS score and change in Health Assessment Questionnaire and McMaster-Toronto Arthritis Patient Preference Disability Questionnaire scores was fair to moderate, whereas changes in MHISS score were poorly or not correlated to other measures. For patients considering their state deteriorated, the MHISS scale was the most responsive instrument. The CHFS and MHISS scores may be useful in detecting changes in location-specific limitations in activity for SSc patients.

The outcome and cost-effectiveness of nurse-led care in the community for people with rheumatoid arthritis: a non-randomised pragmatic study

ObjectiveTo determine the outcome and cost-effectiveness of nurse-led care in the community for people with rheumatoid arthritis (RA).DesignNon-randomised pragmatic study.SettingPrimary (7 primary care practices) and secondary care (single centre) in...

Updated systematic review and meta-analysis of randomized controlled trials comparing low- versus high-dose rituximab for rheumatoid arthritis.

Thepurpose of this study is to update a systematic review and meta-analysis comparing low- (2 × 500 or 1 × 1000mg) and high-dose (2 × 1000mg) rituximab (RTX) for the treatment of rheumatoid arthritis (RA), considering the recent emergence of new evidence. The systematic literature review searching for randomized controlled trials (RCTs) was updated to November 6, 2014 using the PubMed, EMBASE, Cochrane Library, Web of Science databases, and hand searching. The primary outcomes were the American College of Rheumatology (ACR) criteria for 20% improvement (ACR20), ACR50, and ACR70 responses and the Disease Activity Score in 28 joints (DAS28) at 24 and 48/52weeks. The secondary outcomes were change in Health Assessment Questionnaire (HAQ) score, change in the radiographic modified Total Sharp Score (mTSS), levels of immunoglobulin G (IgG), and adverse events. In total, seven RCTs were identified, including two new full publication versions and one abstract of RCTs. There were no significant differences in the primary outcomes and change in HAQ, although the mean change in mTSS was 0.25 units (95% CI, 0.01 to 0.49; P = 0.04) higher in low-dose group at week 52. Two RCTs did not demonstrate difference between the RTX regimens for maintaining clinical response (obtained initially using high-dose RTX) in anti-TNF-experienced patients. IgG levels were significantly higher (P ≤ 0.02), and first infusion reactions were less frequent in the low-dose group (P = 0.02). Our updated results further support the similar efficacy of both RTX regimens in different subsets of RA patients, demonstrating a better clinical and laboratory safety profile of the low-dose scheme.

OP0127 Impact of Disease Activity and Treatment on Progression of Functional Limitation in RA

BackgroundFunctional limitation is a key outcome in rheumatoid arthritis and a key driver of the cost of RA in health economic models. Due to restrictive inclusion/exclusion criteria and short follow...

THU0181 Short-Lasting Flares and HAQ Impairment in Rheumatoid Arthritis Patients in Remission According to the New Acr/Eular Criteria

BackgroundThe new remission criteria suggested by the ACR/EULAR study group for trials [1] are applied in the clinical practice, although they are considered rather strict [2]. Notwithstanding this criteria, patients...

THU0318 Real-Life Assessment of the Validity of Patient Global Impression of Change in Fibromyalgia

BackgroundAssessing fibromyalgia (FM) is challenging due to the lack of hard outcomes and the need to rely on patient-reported symptoms. Completion of questionnaires by patients may be fraught with inaccuracy,...

Is Tightly Controlled Disease Activity Possible with Online Patient-reported Outcomes?

To evaluate the performance of patient-reported outcomes (PRO) as primary indices for identification and prediction of a 28-joint Disease Activity Score (DAS28)>3.2 among patients with rheumatoid arthritis (RA). Patients with RA completed monthly online PRO [Health Assessment Questionnaire (HAQ), Rheumatoid Arthritis Disease Activity Index (RADAI), visual analog scale (VAS) fatigue] and were clinically assessed every 3 months using the DAS28. Simple descriptive statistics, logistic regression, and the Bayesian joint modeling approach were used to analyze the data. The Bayesian joint model combines the scores and changes in the scores of 3 PRO to predict a DAS28>3.2 at the subsequent timepoint. A group of 159 patients with RA participated. Stratified summaries of the PRO by DAS28 categories at baseline provided incremental values of the PRO for more active disease. However, on an individual level, the DAS28 and the PRO fluctuated over time. The prediction of subsequent DAS score by a single instrument at single timepoints resulted in moderate sensitivity and specificity. Using the intercept and slope of the combined PRO of the first 3 measurements to predict the DAS28 state at 3 months resulted in a sensitivity of 0.81 and a specificity of 0.92. After 10-fold cross validation, the model had a sensitivity of 0.61 and specificity of 0.75 to identify patients with a DAS28>3.2. PRO showed fluctuating levels of disease activity over time, while on a group level disease activity stayed the same. Using the changes in RADAI, HAQ, and VAS fatigue over time to predict future DAS28>3.2 resulted in moderate performance after the internal cross-validation of the model (sensitivity 0.61, specificity 0.75).

Comparative effectiveness of cycling of tumor necrosis factor-α (TNF-α) inhibitors versus switching to non-TNF biologics in rheumatoid arthritis patients with inadequate response to TNF-α inhibitor using a Bayesian approach

Alternative tumor necrosis factor-α (TNF-α) inhibitors and non-TNF biologics are available as treatment options for rheumatoid arthritis patients who exhibit inadequate response to TNF-α inhibitor (TNF-IR patients). These agents have considerable efficacy compared with placebo, but head-to-head comparisons among these agents have not been performed. The objective of this study was to use Bayesian approach to compare the effectiveness of cycling TNF-α inhibitors versus switching to non-TNF biologics in TNF-IR patients. A systematic review was conducted using MEDLINE and Cochrane library. Key endpoints were the American College of Rheumatology (ACR) responses of 20/50/70 and the health assessment questionnaire (HAQ) score change at six months. Bayesian outcomes were calculated as the probability that OR is greater than one and HAQ score change difference is less than zero. Compared with TNF-α inhibitors, non-TNF biologics were associated with higher ACR response rates; in ACR20, the OR was 1.639 for abatacept [P(OR > 1) = 90.7 %], 1.871 for rituximab [P(OR > 1) = 96.2 %] and 3.52 for tocilizumab [P(OR > 1) = 99.9 %]. Similar trends were shown in the HAQ change comparison; the median differences (MD) were -0.259 for abatacept [P(MD < 0) = 100 %], -0.160 for rituximab [P(MD < 0) = 98.2 %], and -0.200 for tocilizumab [P(MD < 0) = 99.3 %]. In conclusion, switching to non-TNF biologics was more effective than cycling TNF-α inhibitor in TNF-IR patients.

Smoking in combination with antibodies to cyclic citrullinated peptides is associated with persistently high levels of survivin in early rheumatoid arthritis: a prospective cohort study

IntroductionHigh levels of the oncoprotein survivin may be detected in the majority of patients with early rheumatoid arthritis (RA). Survivin is a sensitive predictor of joint damage and persistent disease activity. Survivin-positive patients are often poor responders to antirheumatic and biological treatment. The aim of this study was to investigate the reproducibility of survivin status and its significance for clinical and immunological assessment of RA patients.MethodsSurvivin levels were measured in 339 patients from the Better Anti-Rheumatic FarmacOTherapy (BARFOT) cohort of early RA at baseline and after 24 months. The association of survivin status with joint damage (total Sharp-van der Heijde score), disease activity (Disease Activity Score based on evaluation of 28 joints (DAS28)), functional disability (Health Assessment Questionnaire (HAQ)), and pain perception (Visual Analogue Scale (VAS)) was calculated in the groups positive and negative for survivin on both occasions, and for the positive-negative and negative-positive groups.ResultsIn 268 patients (79%) the levels of survivin were similar at baseline and after 24 months, 15% converted from survivin-positive to survivin-negative, and 5% from survivin-negative to survivin-positive. A combination of smoking and antibodies against cyclic citrullinated peptides (aCCP) predicted persistently (baseline and 24 months) high levels of survivin (odds ratio 4.36 (95% CI: 2.64 to 7.20), P < 0.001), positive predictive value 0.66 and specificity 0.83). The independent nature of survivin and aCCP was demonstrated by statistical and laboratory analysis. Survivin positivity on both test occasions was associated with the progression of joint damage, significantly higher DAS28 and lower rate of remission at 24 and 60 months compared to negative-negative patients. Survivin status was less associated with changes in HAQ and VAS.ConclusionsSurvivin is a relevant and reproducible marker of severe RA. Persistently high levels of survivin were associated with smoking and the presence of aCCP and/or RF antibodies and predicted persistent disease activity and joint damage.