Baseline Health Assessment Questionnaire Research Articles

Time-averaged DAS28 and HAQ predict cardiovascular disease in patients with rheumatoid arthritis: Data from KORONA registry.

To evaluate the predictive role of time-averaged disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ) on cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA). Patients with RA were recruited from 23 tertiary hospitals. Baseline and annual follow-up data of demographic, laboratory, questionnaire, RA-associated parameters, and occurrence of CVD were collected. Patients were divided into three groups according to time-averaged DAS28: 1) remission (<2.6), 2) low (2.6-3.2), 3) moderate (3.2-5.1), and 4) high (>5.1). Kaplan-Meier curves was performed to compare the cumulative probability of CVD. Hazard ratios of each factor on the occurrence of CVD were obtained using Cox regression analyses. A total of 4,034 RA patients with 826 for remission, 938 for low, 2,002 for moderate, and 268 for high time-averaged DAS28 groups were included. Baseline age, disease duration, ESR, CRP, DAS28, and HAQ scores were higher in the high time-averaged DAS28 group. The incidence rate of CVD was 2.86, 2.71, 3.53, and 8.13 events per 1,000 person-years for the remission, low, moderate, and high time-averaged DAS28 groups, respectively. The incidence rate ratio of CVD in the high time-averaged DAS28 group were 3.01 (95% CI 1.20-8.50) when compared to low time-averaged DAS28 group. The cumulative hazard for CVD in the high time-averaged DAS28 group was significantly high (log-rank P<0.01). In multivariate Cox regression analysis, age, high time-averaged DAS28, and time-averaged HAQ>0.5, were positively associated with CVD events in RA patients. In patients with RA, time-averaged DAS28 and HAQ could predict the occurrence of CVD. Clinical Research Information Service of South Korea https://cris.nih.go.kr: KCT0000086, registered May 26, 2009.

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.

Successful psychopharmacotherapy of anxiety and depressive disorders improve functional limitations in patients with rheumatoid arthritis

To compare changes in functional limitations in patients with rheumatoid arthritis (RA) and comorbid anxiety and depressive disorders (ADD) treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone or in combination with biologic DMARDs (bDMARDs) and/or psychopharmacotherapy (PPT), and to determine predictors of HAQ treatment response. 128 RA-patients were enrolled, 86% were women with a mean age of 47.411.3 (MSD) years and a median of RA duration 96 [48; 228] months. Disease activity was assessed using DAS28, functional limitations using Health Assessment Questionnaire (HAQ). The Minimal Clinical Important Difference in HAQ was considered to be 0.22. ADD were diagnosed by a licensed psychiatrist in 123 (96.1%) of RA-pts in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with MontgomeryAsberg Depression Rating Scale and Hamilton Anxiety Rating Scale. RA-pts with ADD were divided into the following treatment groups: 1 сsDMARDs (n=39), 2 сsDMARDs + PPT (sertraline or mianserine; n=43), 3 сsDMARDs + bDMARDs (n=32), 4 сsDMARDs + bDMARDs + PPT (sertraline or mianserine; n=9); 83 (67.5%) patients were assessed at 5-years follow-up. Multivariable logistic regression was performed to determine predictors of HAQ treatment response. Only remission of anxiety and depressive symptoms at 5-yrs endpoint (OR 6.6, 95% CI 1.7824.43, p=0.005), higher baseline HAQ (OR 2.61, 95% CI 1.126.11, p=0.027) and lower baseline BMI (OR 0.9, 95% CI 0.850.96, p=0.001) were independently associated with HAQ treatment response at 5-years follow-up. While ADD do affect functional limitations in patients with RA, PPT tends to attenuate the negative impact of ADD on RA outcomes, and RA patients with functional limitations should therefore be screened for depression and long-term PPT should be recommended.

Patient-reported outcomes in Chinese rheumatoid arthritis patients: a systematic review and meta-analysis.

Patient-reported outcomes in Chinese rheumatoid arthritis patients: a systematic review and meta-analysis.

O06 Baseline predictors of methotrexate-related adverse events in methotrexate-naïve patients with RA

Abstract Background/Aims Methotrexate (MTX) is the most common treatment for rheumatoid arthritis (RA). The prevalence of adverse events (AEs) associated with MTX treatment for RA have been studied extensively, but there are limited data on the predictors of these AEs. This study aims to summarise the prevalence rates of MTX AEs, including gastrointestinal (GI), neurological, mucocutaneous, and elevated alanine transaminase (ALT) enzyme, and to identify baseline demographic and clinical predictors of these AEs. Methods The Rheumatoid Arthritis Medication Study (RAMS) is a UK multi-centre prospective cohort study of patients with RA starting MTX for the first time. Relevant demographic, medication, clinical and disease related data were collected at baseline. AEs were reported at six and twelve months follow-ups. The prevalence rates of AEs were calculated based on the proportions of patients who reported having had an AE within one year of follow-up. The associations between candidate baseline predictors and AEs were assessed using multivariable logistic regression. Results A total of 2,089 patients were included with a mean age of 58.4 (standard deviation: 13.5) years, 1390 (66.5%) were women. 1,814 and 1,579 patients completed the 6 and 12 months follow-up visits, respectively. The prevalence rates of the AEs within one year of follow-up were: GI = 777 (40.6%), mucocutaneous = 441 (23.1%), neurological = 487 (25.5%), elevated ALT (> upper limit of normal [ULN]) = 286 (15.5%). Younger age and being a woman were associated with increased risk of GI AEs, (age: OR 0.97 per year increase in age, 95% CI 0.98, 1.00; male sex: OR 0.58 vs female, 95% CI 0.46, 0.74) (Table 1). Higher baseline Health Assessment Questionnaire (HAQ) score was an independent predictor of GI, mucocutaneous, and neurological AEs. Furthermore, having ALT >1xULN at baseline or history of diabetes was associated with increased risk of subsequent ALT elevation during the study follow-up. Conclusion In patients with RA starting MTX, GI AEs were the most commonly reported AEs during the first year of follow-up. The identified predictors of AEs may facilitate discussions between clinicians and patients prior to commencing MTX, and may lead to increased adherence and consequently improved effectiveness. Disclosure A.A. Sherbini: None. J.M. Gwinnutt: Grants/research support; BMS. K.L. Hyrich: Member of speakers’ bureau; Abbvie. Grants/research support; Pfizer, UCB, BMS. S.M.M. Verstappen: Consultancies; Celltrion. Member of speakers’ bureau; Pfizer. Grants/research support; BMS.

Health-related Quality of Life Outcomes of Adalimumab for Patients With Rheumatoid Arthritis in Korea.

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disorder that impairs patients' overall health-related quality of life (HRQOL) In this study, we evaluated the effect of adalimumab in Korean patients with active RA on HRQOL. Patients included in the study had moderate to severe active RA that did not respond to conventional drugs with a Disease Activity Score of 28 joints >32 and were biologics-naïve All patients received adalimumab 40 mg subcutaneously every other week and were followed for 24 weeks The primary endpoint was the change in baseline Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24 Secondary endpoints were changes in the EuroQol 5-dimension 3-Level (EQ-5D-3L) baseline score and Short Form 36-Item Health Survey (SF-36) domain scores at weeks 12 and 24 and change in baseline HAQ-DI score at week 12. In total, 91 Korean patients were included Ninety-three percent of patients were in high disease activity with a baseline mean DAS28 value of 61 within all patients The mean change from baseline in HAQ-DI scores were -046 at week 12 and∼067 at week 24 (p<00001) Additionally, EQ-5D-3L score at weeks 12 and 24 had significantly improved (p<00001) compared to baseline SF-36 at weeks 12 and 24 had significantly improved (p<00001, p=00001) compared to baseline. Treatment with adalimumab resulted in significant improvement in HAQ-DI, EQ-5D-3L, and SF-36 scores at 12 and 24 weeks in Korean RA patient.

Heterogenous bone response to biologic DMARD therapies in rheumatoid arthritis patients and their relationship to functional indices

Objectives: Previous studies of high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of hand joints in patients with rheumatoid arthritis (RA) have suggested that erosion healing may occur. Our objective was to examine changes in erosion volume, joint space width (JSW), bone mineral density (BMD), and bone remodelling, and their association with clinical outcomes and measures of patient hand function. Method: We examined 48 patients who achieved a good response to a newly initiated biologic therapy. HR-pQCT images of the dominant hands’ second and third metacarpophalangeal joints were obtained 3 and 12 months after therapy initiation. Bone erosion volume, JSW, BMD, and bone remodelling were quantified from HR-pQCT images, with improvement, no change (unchanged), or progression in these measures determined by least significant change. Disease activity and hand function measures were collected. Results: There were no significant group changes in HR-pQCT outcomes over the 9 month period. Twenty-two patients had total erosion volumes that remained unchanged, nine showed improvement, and two progressed. The majority of JSW and BMD measures remained unchanged. There was a significant association between the baseline Health Assessment Questionnaire score and the change in minimum JSW, but no other significant associations between HR-pQCT outcomes and function were observed. Conclusions: The vast majority of patients maintained unchanged JSW and BMD over the course of follow-up. Significant improvements in total erosion volume occurred in 27% of patients, suggesting that biologic therapies may lead to erosion healing in some patients, although this did not have an impact on self-reported and demonstrated hand function.

Characterization of disease course and remission in early seropositive rheumatoid arthritis: results from the TACERA longitudinal cohort study.

Background:To characterise disease course and remission in a longitudinal observational study of newly diagnosed, initially treatment-naïve patients with seropositive rheumatoid arthritis (RA).Methods:Patients with early untreated seropositive RA were recruited from 28 UK centres. Multiple clinical and laboratory measures were collected every 3 months for up to 18 months. Disease activity was measured using the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI). Logistic regression models examined clinical predictors of 6-month remission and latent class mixed models characterised disease course.Results:We enrolled 275 patients of whom 267 met full eligibility and provided baseline data. According to SDAI definition, 24.3% attained 6-month remission. Lower baseline Health Assessment Questionnaire (HAQ) and SDAI predicted 6-month remission (p = 0.013 and 0.011). Alcohol intake and baseline prescribing of methotrexate with a second disease-modifying antirheumatic drug (DMARD; vs monotherapy without glucocorticoids) were also predictive. Three distinct SDAI trajectory subpopulations emerged; corresponding to an inadequate responder group (6.5%), and higher and lower baseline activity responder groups (22.4% and 71.1%). Baseline HAQ and Short Form-36 Health Survey – Mental Component Score (SF-36 MCS) distinguished these groups. In addition, a number of baseline clinical predictors correlated with disease activity severity within subpopulations. Beneficial effects of alcohol intake were found across subpopulations.Conclusion:Three distinct disease trajectory subpopulations were identified. Differential effects of functional and mental well-being, alcohol consumption, and baseline RA medication prescribing on disease activity severity were found across subpopulations. Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors. We hypothesise that biological markers collected early in disease course (within 6 months) may help patient management and better targeting of existing and novel therapies.

Relation Between Fatigue and ACR Response in Patients With Psoriatic Arthritis Treated With Tumor Necrosis Factor Inhibitor Therapy: A Population-based Cohort Study.

The objective of this population-based cohort study was to investigate the association between fatigue with disease activity and drug survival in patients with psoriatic arthritis (PsA) receiving their first tumor necrosis factor inhibitor (TNFi). Data on patient characteristics, disease activity, and drug survival were obtained from the DANBIO database on all patients with PsA from 2006 through 2015. Information on comorbidities was obtained through linkage with the Danish National Patient Registry. A total of 880 patients were eligible for analyses. Patients with upper median fatigue scores had statistically significant higher disease activity measures (Disease Activity Score in 28 joints based on C-reactive protein), pain, and Health Assessment Questionnaire (HAQ) scores; tender joint counts; comorbidities (Charlson Comorbidity Index ≥ 2); and current smoking status at baseline compared to patients with lower median fatigue scores (P < 0.05). In the upper median fatigue group, fewer patients achieved American College of Rheumatology (ACR) responses and improvements in visual analog scale (VAS) fatigue compared to patients in the lower median fatigue group. Kaplan-Meier curves showed shorter drug survival in patients in the upper median fatigue group compared with the lower median fatigue group at 6-month follow-up. Fatigue remains a dominating symptom after TNFi treatment, and is associated with higher baseline disease activity, pain, and HAQ scores; more comorbidities; and increased risk of TNFi treatment discontinuation in a cohort of Danish patients with PsA. The agreement between ACR and VAS fatigue responses is weak to moderate, suggesting heterogeneity between experienced fatigue and joint inflammation.

PMS28 COST-UTILITY ANALYSIS OF TREATMENT OPTIONS AFTER INITIAL TUMOR NECROSIS FACTOR INHIBITOR THERAPY FAILURE IN PATIENTS WITH RHEUMATOID ARTHRITIS

To use real-world data to analyze the cost-utility of sequences of therapeutic drugs used by rheumatoid arthritis patients whose initial tumor necrosis factor inhibitor therapy failed. We developed a microsimulation Markov model to analyze 10,000 rheumatoid arthritis patients (80% female, mean age 52yrs) beginning their second biological treatment with adalimumab (cycling) or abatacept (swapping) and followed them for 10 years or until death. Patients not responding switched to the next drug in a sequence of three (adalimumab-abatacept-tocilizumab versus abatacept-tocilizumab-rituximab) and then shifted to palliative treatment. Demographics, the most common drug choice per cycling or swapping cohorts, subsequent treatment sequences, direct medical costs, and transition probabilities were derived from a cohort of rheumatoid arthritis patients in the 2008-2016 Truven Health MarketScan Research database. Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) were derived from an age-adjusted comorbidity index and converted to utilities using the formula from the Birmingham Rheumatoid Arthritis Model. Scenario analysis was used to vary the time horizon, utility formula and baseline HAQ-DI. We also performed a probabilistic sensitivity analysis. Swapping to a sequence beginning with abatacept showed an incremental discounted cost of $11,357 over ten years and achieved a discounted cost per quality-adjusted life year (QALY) benefit of 0.16 compared with cycling to adalimumab. The incremental cost-effectiveness ratio of $68,950/QALY was within current willingness-to-pay thresholds. Scenario analysis produced an incremental cost-effectiveness ratio range of $44,573/QALY to $148,558/QALY: abatacept was more cost-effective over longer periods of time and when baseline HAQ was lower. Probabilistic sensitivity analysis showed that swapping to abatacept after tumor necrosis factor inhibitor therapy failure had an 80.6% likelihood of being cost-effective at $100,000/QALY. Abatacept is a cost-effective strategy for rheumatoid arthritis patients whose initial tumor necrosis factor inhibitor therapy fails. Being able to stratify patients by reason for switch would improve the validity of our conclusions.

Predicting Remission Among Patients With Rheumatoid Arthritis Starting Tocilizumab Monotherapy: Model Derivation and Remission Score Development.

ObjectiveMost patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score.MethodsWe identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score.ResultsThe variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease‐modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%‐25% probability), and 15% in the moderate remission prediction category (greater than 25% probability).ConclusionWe used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.

Real-world Longterm Effectiveness of Tumor Necrosis Factor Inhibitors in Psoriatic Arthritis Patients from the Rheumatic Diseases Portuguese Register.

To assess longterm effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with psoriatic arthritis (PsA) registered in the Rheumatic Diseases Portuguese Register, exposed to at least 1 TNFi, prospectively followed between 2001 and 2017. Kaplan-Meier analysis was performed for first-, second-, and third-line TNFi. Responses included European League Against Rheumatism (EULAR) criteria, Disease Activity Index for Psoriatic Arthritis (DAPSA), minimal disease activity (MDA), and Ankylosing Spondylitis Disease Activity Score (ASDAS) at 3 and 6 months. Baseline predictors of discontinuation and response were studied using Cox and multivariable multinomial/logistic regression models. The 750 patients with PsA showed drug retention of 4.1 ± 3.4 years (followup 5.8 ± 3.8 yrs) for first TNFi. Switching to a second (189 patients) or third (50 patients) TNFi further decreased survival by 1.1 years. Female sex, higher baseline 28-joint count Disease Activity Score, and infliximab were predictors of first TNFi discontinuation. After 6 months of the first TNFi, 48.7% of patients achieved a good EULAR criteria response and 20.9% were in DAPSA remission. There were 11.4% in MDA, and 56.4% had a good ASDAS. Responses to the second TNFi were significantly inferior compared to responses to the first TNFi. Female sex and higher baseline Health Assessment Questionnaire-Disability Index were negatively associated with good EULAR response at 3 months, and obesity decreased the chance of response at 6 months. In this study, switching to a second or third TNFi was associated with significantly lower drug survival and response rates for patients with axial and peripheral PsA subtypes. More successful therapeutic approaches will require considering the effect of sex and obesity on TNFi effectiveness.

Not all moderate disease is the same - Identification of disability trajectories among patients with rheumatoid arthritis and moderate disease activity.

BackgroundUnited Kingdom guidelines for the use of biologic disease modifying anti-rheumatic drugs (bDMARDS) for rheumatoid arthritis (RA) require patients to have active disease (Disease Activity Score [DAS28] >5.1) and have failed ≥2 previous conventional synthetic DMARDs (csDMARD). Patients with moderate disease activity (MDA) do not meet these criteria, yet often have poor outcomes. This study aimed to identify trajectory groups of disability scores over three years in RA patients with MDA.MethodsThe study included biologic-naïve patients receiving csDMARDs only with MDA (3.2 <DAS28≤ 5.1) when recruited to the control cohort of the British Society for Rheumatology Biologics Register–RA (BSRBR-RA). Disability scores, measured using the Health Assessment Questionnaire (HAQ), were recorded every six months for three years. Trajectories of HAQ scores over follow-up were assessed using latent class growth models (LCGMs). Baseline age, gender, DAS28, symptom duration, rheumatoid factor status, number of prior csDMARDs and co-morbidities were assessed as potential predictors of group membership.ResultsIn total, 1274 patients were included (mean age: 61 years (standard deviation: 12), 71.4% women). The best fitting model included seven HAQ trajectories. These trajectories were horizontal over follow-up and were related to baseline HAQ: very-low (6.8%, baseline (BL) HAQ: 0.22), low (11.5%, BL HAQ: 0.41), low-moderate (17.0%, BL HAQ: 0.93), moderate (13.4%, BL HAQ: 1.09), high-moderate (19.5%, BL HAQ: 1.61), severe (23.2%, BL HAQ: 1.98) and very-severe (8.6%, BL HAQ: 2.54). Higher DAS28, older age, female gender, longer disease duration and more co-morbidities were independently associated with higher HAQ trajectory group.ConclusionThere is substantial heterogeneity in baseline HAQ scores in this population, and the trajectories of HAQ scores after baseline are, on average, relatively flat. As bDMARD therapy has been shown to improve HAQ scores, patients with MDA but high HAQ scores may benefit from a more aggressive approach to therapy.

Simplified disease activity changes in real-world practice: a nationwide observational study of seropositive rheumatoid arthritis patients with moderate-to-high disease activity.

Background/AimsThe objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheumatoid arthritis (RA) in daily clinical practice.MethodsThis was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Serial SDAI changes and clinical remission rate at 6 and 12 months were assessed.ResultsA total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was –19.0 in the bDMARD group and –12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, respectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission.ConclusionsThere was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

Discrete Trajectories of Resolving and Persistent Pain in People With Rheumatoid Arthritis Despite Undergoing Treatment for Inflammation: Results From Three UK Cohorts

Rheumatoid arthritis (RA) is an example of human chronic inflammatory pain. Modern treatments suppress inflammation, yet pain remains a major problem for many people with RA. We hypothesized that discrete RA subgroups might display favorable or unfavorable pain trajectories when receiving treatment, and that baseline characteristics will predict trajectory allocation. Growth mixture modelling was used to identify discrete trajectories of Short Form-36 bodily pain scores during 3 years in 3 RA cohorts (Early RA Network (n = 683), British Society for Rheumatology Biologics Register Biologics (n = 7,090) and nonbiologics (n = 1,720) cohorts. Logistic regression compared baseline predictor variables between trajectories. The role of inflammation was examined in a subgroup analysis of people with normal levels of inflammatory markers after 3 years. The mean Short Form-36 bodily pain scores in each cohort improved but remained throughout 3 years of follow-up of >1 standard deviation worse than the UK general population average. Discrete persistent pain (59–79% of cohort participants) and resolving pain (19–27%) trajectories were identified in each cohort. In Early RA Network, a third trajectory displaying persistently low pain (23%) was also identified. In people with normal levels of inflammatory markers after 3 years, 65% were found to follow a persistent pain trajectory. When trajectories were compared, greater disability (adjusted odds ratio = 2.3–2.5 per unit baseline Health Assessment Questionnaire score) and smoking history (adjusted odds ratio = 1.6–1.8) were risk factors for persistent pain trajectories in each cohort. In conclusion, distinct trajectories indicate patient subgroups with very different pain prognosis during treatment for RA. Inflammation does not fully explain the pain trajectories, and noninflammatory factors as well as acute phase response predict which trajectory an individual will follow. Targeted treatments additional to those which suppress inflammation might reduce the long-term burden of arthritis pain. PerspectiveImmunosuppression decreases inflammation in RA, but pain outcomes are less favorable. Discrete persistent and resolving pain trajectories were identified after treatment, both in early and established RA. Smoking and greater disability at baseline predicted persistent pain. Identifying patient subgroups with a poor pain prognosis could enable adjunctive treatment to improve outcomes.

PMU67 - COST-EFFECTIVENESS ANALYSIS OF IXEKIZUMAB VERSUS SECUKINUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS AND CONCOMITANT MODERATE-TO-SEVERE PSORIASIS IN THE UNITED KINGDOM

Biologic disease-modifying antirheumatic drugs (bDMARDs) are a major driver of total costs in psoriatic arthritis (PsA), a chronic inflammatory rheumatic condition associated with psoriasis. To date, there are no cost-effectiveness analyses (CEAs) comparing the interleukin-17A antagonists ixekizumab and secukinumab in PsA in the UK. We conducted a CEA from the UK National Health Service perspective to compare the cost-effectiveness of ixekizumab versus secukinumab in bDMARD-naïve patients with PsA and concomitant moderate-to-severe psoriasis. A Markov model derived from the widely accepted York model was developed. The model used a lifetime horizon with monthly cycles. Treatment sequences evaluated were ixekizumab→ustekinumab→best supportive care (BSC) versus secukinumab→ustekinumab→BSC. The model included the health states trial bDMARD period, continuous bDMARD treatment, BSC and death. At the end of the bDMARD trial period, Psoriatic Arthritis Response Criteria (PsARC) responders transitioned to continuous treatment with trial bDMARD. PsARC non-responders and patients who discontinued continuous treatment transitioned to trial period of next bDMARD or BSC, as appropriate. Clinical efficacy was measured in terms of proportion of patients achieving a PsARC response and change from baseline Health Assessment Questionnaire – Disability Index (HAQ-DI) and Psoriasis Area Severity Index (PASI) scores, which were derived from network meta-analyses. Health utilities were estimated by applying regression analysis to HAQ-DI and PASI scores collected in the SPIRIT trials with ixekizumab in PsA. Only direct medical costs were included. Ixekizumab was associated with lower total costs (£155,455 vs £155,530 [year of costing 2017]) and higher total QALYs (8.127 vs 7.989) than secukinumab, although differences were modest. Robustness of results was assessed through deterministic and probabilistic sensitivity analyses. In bDMARD-naïve patients with PsA and concomitant moderate-to-severe psoriasis in the UK, first-line ixekizumab in this biologic treatment sequence provided slight advantages in cost savings and QALYs gained over first-line secukinumab in a similar sequence.

HAQ score is an independent predictor of sustained remission in patients with rheumatoid arthritis.

We assessed potential predictors of sustained remission for 2years according to the Disease Activity Score in 28 joints (DAS28)-CRP in patients with rheumatoid arthritis (RA). We obtained data for 290 RA outpatients, from July 2009 to September 2012. Sociodemographic data and answers to questionnaires were collected in face-to-face interviews. Remission was defined according to DAS28-CRP. Sustained remission was defined as meeting criteria for remission in the annual assessment for twoconsecutive years. Predictive factors of sustained remission according to DAS28-CRP were assessed by univariate and multivariate analyses. Of the 290 RA patients, the baseline remission level, according to DAS28-CRP, was 54.5%. During 2years of follow-up, the sustained remission rate was 24.5%. RA patients who achieved sustained remission, according to DAS28-CRP, were younger, and had a shorter duration of symptoms, longer period of education, higher monthly income, lower Health Assessment Questionnaire (HAQ) score, lower physician global assessment, lower patient global assessment, lower patient pain assessment, and higher EQ-5D at baseline. Multivariate analyses showed that the baseline HAQ score was independently associated with sustained remission for 2years according to DAS28-CRP (OR 0.298, 95% CI 0.115-0.770; p=0.012). A lower HAQ score at baseline was an independent predictor of sustained remission at 2years, according to DAS28-CRP. Thus, HAQ scores could be useful when stratifying patients according to risk for flare-ups in the clinic.

Meta-Regression of a Dose-Response Relationship of Methotrexate in Mono- and Combination Therapy in Disease-Modifying Antirheumatic Drug-Naive Early Rheumatoid Arthritis Patients.

To investigate a possible short-term dose-response relationship of initial treatment with methotrexate (MTX) in monotherapy and combination therapy in recent-onset rheumatoid arthritis (RA) patients. A systematic literature search was performed on trials and cohorts, including early, disease-modifying antirheumatic drug (DMARD)-naive RA patients treated with MTX, with data on clinical results within 6 months from treatment start. Cohen's effect sizes were calculated for the Health Assessment Questionnaire (HAQ), erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) level, and/or Disease Activity Score (DAS)/in 28 joints (DAS28) in 4 treatment groups: MTX monotherapy, or MTX in combination with synthetic (cs) DMARDs, biologic (b) DMARDs, or glucocorticoids. Random-effects meta-regression analyses were performed for each outcome, with treatment group as the predictor corrected for baseline HAQ or disease activity and assessment point. Thirty-one studies including 5,589 patients were included. The meta-regression did not support higher effectiveness of increasing MTX dose in monotherapy. The number of treatment groups using combination therapy with csDMARDs was too small to perform meta-regression analyses. In combination therapy with glucocorticoids, a higher MTX dose was associated with higher (worse) outcome HAQ, but not with DAS/DAS28 or ESR/CRP level. In combination therapy with bDMARDs, a higher MTX dose was associated with higher outcome HAQ and DAS/DAS28, but not with ESR/CRP level. All effect sizes were small. In DMARD-naive, early RA patients who start MTX, either as monotherapy or in combination with bDMARDs or glucocorticoids, a higher initial dose of MTX was not associated with better clinical outcomes. This finding suggests that there is little short-term gain from starting with high compared to low MTX doses.

Real-world validation of the minimal disease activity index in psoriatic arthritis: an analysis from a prospective, observational, biological treatment registry

ObjectiveTo describe the minimal disease activity (MDA) rate over time in patients with psoriatic arthritis (PsA) receiving antitumour necrosis factor agents, evaluate prognostic factors of MDA achievement and identify the...

Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators

Aims: To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs.Materials and methods: An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY.Results: For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs.Conclusions: bDMARD treatment sequences are cost-effective from a US societal perspective.