Change In Health Assessment Questionnaire Disability Index Research Articles

P170 Ixekizumab significantly improved quality of life and joint pain in patients with psoriatic arthritis, nail disease and distal interphalangeal joint involvement from SPIRIT-H2H

Abstract Background/Aims Among adults with psoriatic arthritis (PsA) in the SPIRIT H2H study, 65% had nail psoriasis (PsO) at baseline and of these, 96.2% had simultaneous distal interphalangeal joint (DIP) disease in ≥ 1 digits at baseline. This analysis describes the impact of ixekizumab (IXE) and adalimumab (ADA) on quality of life (QoL), function and joint pain. Methods This post-hoc analysis included patients from SPIRIT-H2H (NCT03151551) treated with either IXE or ADA who had simultaneous nail and DIP involvement (swelling or tenderness) in ≥ 1 digits at baseline. Nail PsO was measured using Nail Psoriasis Severity Index (NAPSI). Joint involvement was measured by tender/swollen joint count scores. Joint pain was measured by patient’s assessment of pain using Visual Analogue Scale (100 mm). QoL measures included Dermatology Life Quality Index (DLQI), Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 Mental and Physical Component Summary Scores (SF-36 MCS/PCS). Patients were evaluated at baseline and Week 4, 8, 12, 16, 24, 32, 40, and 52. Joint pain and SF-36 MCS/PCS changes from baseline were analysed using a mixed effects model of repeated measures. Proportions of patients achieving DLQI ≤1 or HAQ-DI change ≥0.35 (minimal clinically important difference) were analysed using logistic regressions. Non-responder imputation and modified baseline observation carried forward methods were used for missing data. Results 354 SPIRIT-H2H patients had a NAPSI total score >0 and DIP involvement in ≥ 1 digits simultaneously at baseline (IXE, N = 186 and ADA, N = 168). Among them, IXE-treated patients had a significant improvement in joint pain at Week 4 and a larger improvement in joint pain over 52 weeks vs ADA-treated patients. In addition, a larger proportion of IXE-treated patients achieved a DLQI score of 0 or 1, and these statistically significant differences were observed as early as Week 4 and sustained at each visit over 52 weeks. IXE-treated patients also experienced statistically significant improvements in SF-36 MCS at Week 4, 12 and 32 compared to ADA-treated patients; numerically greater improvements in favor of IXE were sustained at all other visits. IXE-treated patients showed a larger improvement in SF-36 PCS over 52 weeks vs ADA-treated patients, and these differences reached statistical significance at Week 24 and 32. Similar proportions of patients treated with IXE or ADA showed a clinically important improvement in HAQ-DI. Conclusion In patients with simultaneous nail and DIP involvement in ≥ 1 digit at baseline, IXE treatment resulted in significant improvements across multiple QoL measures, and greater improvements in joint pain compared to ADA treatment. These data may help health care providers make clinical decisions concerning the care of PsA in patients with nail and DIP involvement. Disclosure C. Ritchlin: Consultancies; C. Ritchlin has received consulting fees and/or honoraria and/or grant support from: AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB Pharma. A. Kavanaugh: Consultancies; A. Kavanaugh has received consulting fees and/or honoraria from: AbbVie, Eli Lilly and Company, Janssen, Novartis, Pfizer, UCB Pharma. L. Kristensen: Consultancies; L.E. Kristensen has received consulting fees and/or honoraria and/or research support from: Pfizer, AbbVie, Amgen, UCB Pharma, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly and Company, Janssen. J. Merola: Consultancies; J. F. Merola is a consultant and/or investigator for: Amgen, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly and Company, Novartis, Janssen, UCB Pharma, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer. B. Strober: Corporate appointments; B. Strober has been serving as an Editor-in-Chief for the Journal of Psoriasis and Psoriatic Arthritis; and serving as scientific co-director and investigator for CorEvitas Psoriasis Registry. Consultancies; B. Strober has served as a speaker for and/or has received consulting fees and/or honoraria from: AbbVie, Alamar, Alumis, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim. Shareholder/stock ownership; reports having stock options in Connect Biopharma, Mindera Health. Honoraria; He is also a consultant for Immunic Therapeutics, Kangpu Pharmaceuticals, Bristol-Myers-Squibb, Connect Biopharma, Dermavant, Evelo Biosciences, Incyte, Janssen, Leo, Eli Lilly and Company, Maruho. Grants/research support; He is also a consultant for Meiji Seika Pharma, Mindera Health, Protagonist, Nimbus, Novartis, Pfizer, UCB Pharma, Sun Pharma, Regeneron, Sanofi-Genzyme, Union Therapeutics, Ventyxbio, vTv Therapeutic. J. Lisse: Consultancies; J. Lisse is employee and stockholder of Eli Lilly and Company. R. Bolce: Shareholder/stock ownership; R. Bolce is employee and stockholder of Eli Lilly and Company. C. Sapin: Shareholder/stock ownership; C. Sapin is employee and stockholder of Eli Lilly and Company. J. Pustizzi: Shareholder/stock ownership; J. Pustizzi is employee and stockholder of Eli Lilly and Company. D. McGonagle: Consultancies; D. McGonagle has received consulting fees and/or honoraria and/or research grants from: AbbVie and Eli Lilly and Company. Grants/research support; His funding sources include or have included the Wellcome Trust-EPSRC, UK NIHR, ARUK, MRC UK and EU FP7 programme.

Health-related quality of life improvement by adalimumab therapy in patients with rheumatoid arthritis in Taiwan: A nationwide prospective study.

To determine the effects of adalimumab on health-related quality of life (HRQoL) in Taiwanese patients with moderate-to-severe rheumatoid arthritis (RA) (NCT02616380). During a 24-week observational period, 100 biologic-naive patients with RA received 40 mg adalimumab subcutaneously, every 2 weeks. The primary endpoint was a change in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at 24 weeks. The secondary endpoints included change in HAQ-DI at week 12, number and percentage of patients achieving a meaningful improvement in HAQ-DI at weeks 12 and 24, and changes in the 36-Item Short Form Health Survey (SF-36), EuroQol 5-dimension 3-level version (EQ-5D-3L) index, and Work Productivity and Activity Impairment (WPAI) questionnaire scores at weeks 12 and 24. At weeks 12 and 24, mean changes in HAQ-DI from baseline were -0.34 ± 0.46 and -0.44 ± 0.59 (both p < 0.001), and clinically meaningful improvement in HAQ-DI was achieved by 60.4% and 59.6% of patients, respectively. SF-36, EQ-5D-3L index, and WPAI scores significantly improved ( p < 0.001) from baseline to weeks 12 and 24. Exploratory analyses showed diabetes was significantly associated with changes in HAQ-DI, EQ-5D-3L, and WPAI scores whereas peptic ulcer correlated with changes in the SF-36 physical component summary T-score. HRQoL improved after initiation of adalimumab therapy in Taiwanese patients with moderate-to-severe RA.

Effects of Locomotion Training on the Physical Functions and Quality of Life in Patients with Rheumatoid Arthritis: A Pilot Clinical Trial.

ABSTRACTObjectives:This study investigated the effects of locomotion training on physical functions and quality of life in patients with rheumatoid arthritis (RA).Methods:Thirty-five patients with RA underwent locomotion training for 6 months. Health data collected from the subjects at baseline and after 6 months were the Health Assessment Questionnaire Disability Index (HAQ-DI), pain Visual Analog Scale, 10-m walking test, Timed Up-and-Go (TUG) test, single-leg standing test, Short Form-8 score with physical and mental component summaries, and 25-question Geriatric Locomotive Function Scale. The primary endpoint was a change in HAQ-DI at 6 months.Results:In terms of the primary outcome, the HAQ-DI significantly improved from 0.48 ± 0.69 at baseline to 0.27 ± 0.36 at 6 months (P=0.011). The significant secondary outcomes were a change in TUG test for comfortable walking from 9.8 ± 2.1 s at baseline to 8.9 ± 2.0 s at 6 months (P=0.002) and increased single-leg standing times for the right and left legs from 24.7 ± 23.5 s and 22.6 ± 22.8 s at baseline to 30.9 ± 22.1 s and 32.4 ± 24.1 s at 6 months (P=0.004, P <0.001), respectively.Conclusions:The findings suggest that locomotion training for 6 months may improve the HAQ-DI in patients with RA.

Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study.

Vagus nerve stimulation delivered with an implanted device has been shown to improve rheumatoid arthritis severity. We aimed to investigate the safety and efficacy of non-invasive stimulation of the auricular branch of the vagus nerve for the treatment of patients with moderately to severely active rheumatoid arthritis. This prospective, multicentre, open-label, single-arm proof-of-concept study enrolled patients aged 18-80 years with active rheumatoid arthritis who had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and up to one biological DMARD. Biological DMARDs were stopped at least 4 weeks before enrolment and concomitant use was not allowed during the study. All eligible participants were assigned to use a non-invasive, wearable vagus nerve stimulation device for up to 30 min per day, which delivered pulses of 20 kHz. Follow-up visits occurred at week 1, week 2, week 4, week 8, and week 12 after the baseline visit. The primary endpoint was the mean change in Disease Activity Score of 28 joints with C-reactive protein (DAS28-CRP) at week 12 compared with baseline. Secondary endpoints included the mean change in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the proportion of patients with a minimal clinically important difference of 0·22 on HAQ-DI, the proportion achieving American College of Rheumatology (ACR) 20, ACR50, and ACR70 response, and safety analysis. This study is registered with ClinicalTrials.gov (NCT04116866). Of 35 patients screened for eligibility, 30 (86%) were enrolled at six centres in Spain between Dec 27, 2018, and Oct 24, 2019, of whom 27 (90%) completed the week 12 visit. The mean change in DAS28-CRP at 12 weeks was -1·4 (95%CI -1·9 to -0·9; p<0·0001) from a mean baseline of 5·3 (SD 1·0). 11 (37%) of 30 patients reached DAS28-CRP of 3·2 or less, and seven (23%) patients reached DAS28-CRP of less than 2·6 at week 12. The mean HAQ-DI change was -0·5 (95%CI -0·7 to -0·2; p<0·0001) from a mean baseline of 1·6 (SD 0·7), and 17 (57%) patients reached a minimal clinically important difference of 0·22 or more. ACR20 responses were reached by 16 (53%) patients, ACR50 responses by 10 (33%) patients, and ACR70 by five (17%) patients. Four adverse events were reported, none of which were serious and all of which resolved without intervention. Use of the device was well tolerated, and patients had clinically meaningful reductions in DAS28-CRP. This was an uncontrolled, open-label study, and the results must be interpreted in this context. Further evaluation in larger, controlled studies is needed to confirm whether this non-invasive approach might offer an alternative treatment for rheumatoid arthritis. Nēsos.

Tofacitinib as monotherapy following methotrexate withdrawal in patients with psoriatic arthritis previously treated with open-label tofacitinib plus methotrexate: a randomised, placebo-controlled substudy of OPAL Balance.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis, rheumatoid arthritis, and ulcerative colitis. This study evaluated the efficacy and safety of tofacitinib 5 mg twice daily monotherapy after methotrexate withdrawal. OPAL Balance was an open-label, long-term extension study of tofacitinib in patients with psoriatic arthritis who participated in the OPAL Broaden and OPAL Beyond phase 3 studies. This 12-month, randomised, double-blind, placebo-controlled, methotrexate withdrawal substudy (50 centres, 14 countries) included patients from OPAL Balance who completed tofacitinib treatment for 24 months or more (≥3 months' stable tofacitinib 5 mg twice daily) and were receiving methotrexate (7·5-20 mg/week). Patients were blindly randomised (1:1) using interactive response technology and received open-label tofacitinib 5 mg twice daily with either placebo (tofacitinib 5 mg twice daily plus placebo group) or continued methotrexate (tofacitinib 5 mg twice daily plus methotrexate group). Patients were masked to placebo or methotrexate, with identical capsules used. Coprimary endpoints were changes from substudy baseline in psoriatic arthritis disease activity score (PASDAS) and health assessment questionnaire-disability index (HAQ-DI) at month 6 in all randomised patients with one or more substudy drug dose. Safety was assessed throughout. No specific statistical hypothesis (either superiority or non-inferiority) was tested. The study (OPAL Balance) is registered with ClinicalTrials.gov (NCT01976364) and is complete. Between Oct 30, 2017, and May 20, 2019, 180 patients from OPAL Balance who were eligible for the substudy were randomly assigned to treatment (90 patients received tofacitinib 5 mg twice daily plus placebo and 89 patients assigned to tofacitinib plus methotrexate; one patient was not treated because of randomisation error). At month 6, least squares mean (LSM) changes in PASDAS were 0·23 (SE 0·08) for tofacitinib 5 mg twice daily plus placebo and 0·14 (0·08) for tofacitinib 5 mg twice daily plus methotrexate (treatment difference LSM 0·09 [95% CI -0·13 to 0·31]), and changes in HAQ-DI were 0·04 (0·03) and 0·02 (0·03), respectively (treatment difference 0·03 [-0·05 to 0·10]). Rates of adverse events, discontinuations because of adverse events, adverse events of special interest, and laboratory changes were generally similar between treatment groups, although liver enzyme elevations were more common with tofacitinib 5 mg twice daily plus methotrexate than tofacitinib 5 mg twice daily plus placebo. Flares of worsening symptoms was reported in one (1%) of 90 patients in the tofacitinib 5 mg twice daily plus placebo group (recorded as psoriatic arthropathy). Some patients with psoriatic arthritis who are stable on tofacitinib 5 mg twice daily with background methotrexate might be able to discontinue methotrexate without clinically meaningful changes in disease activity and safety. Pfizer Inc.

Associations between Patient Global Assessment scores and pain, physical function, and fatigue in rheumatoid arthritis: a post hoc analysis of data from phase 3 trials of tofacitinib

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We examined the degree to which Patient Global Assessment of Disease Activity (PtGA) was driven by patient-reported assessments of pain (Pain), physical function, and fatigue in patients receiving tofacitinib 5 mg twice daily or placebo, each with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).MethodsThis post hoc analysis used data pooled from three randomized controlled trials in csDMARD-inadequate responder (csDMARD-IR) patients (ORAL Scan: NCT00847613; ORAL Standard: NCT00853385; ORAL Sync: NCT00856544). Using subgroup analysis from 2 × 2 tables, associations between PtGA and Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at month 3 were evaluated using Pearson’s Phi correlation coefficients. To support the main analysis, associations between select patient-reported outcomes (PROs) were also evaluated in csDMARD-naïve (ORAL Start; NCT01039688) and biologic (b)DMARD-IR (ORAL Step; NCT00960440) patients.ResultsAcross csDMARD-IR treatment groups, low disease activity (defined as PtGA ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in PtGA were associated with mild Pain (Visual Analog Scale score ≤ 20 mm), and moderate (≥ 30%) and substantial (≥ 50%) improvements from baseline in Pain; lack of Pain improvement was associated with little/no improvement in PtGA. In contrast, large proportions of csDMARD-IR patients who reported PtGA improvements did not report HAQ-DI or FACIT-F scores ≥ normative values (≤ 0.25 and ≥ 43.5, respectively) or changes in HAQ-DI or FACIT-F scores ≥ minimum clinically important difference (≥ 0.22 and ≥ 4.0, respectively). Generally, PtGA and Pain outcomes were moderately-to-strongly correlated at month 3 in csDMARD-IR patients, with weaker correlations evident between PtGA and HAQ-DI/FACIT-F outcomes. Similar findings were generally evident in csDMARD-naïve and bDMARD-IR patients.ConclusionsThis analysis supports the role of Pain as a key driver of PtGA in RA; physical function and fatigue play lesser roles in patients’ perceptions of disease activity. These findings corroborate the importance of improved PROs and attainment of low symptom states for optimizing patient care.Trial registrationClinicaltrials.gov: NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009); NCT01039688 (registered: December 25, 2009); NCT00960440 (registered: August 17, 2009)

A new laboratory surrogate (Monocyte Chemotactic Protein-1) for Disease Activity Score28: a favourable indicator for remission in rheumatoid arthritis

This prospective one-year follow-up study was conducted from 835 visits in 178 rheumatoid arthritis (RA) patients. Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months. Radiographs of hands and feet were acquired at baseline and one year. We evaluated the correlation and accuracy of activity scores in predicting remission, HAQ-DI changes and radiographic changes. DAS28-MCP-1 correlated strongly with DAS28-ESR, DAS28-CRP and SDAI scores (0.830, 0.899 and 0.931, respectively, with all P < 0.001). Score changes of DAS28-MCP-1 were comparable to those of DAS28-ESR, DAS28-CRP and SDAI in predicting changes in HAQ-DI and bone erosion. DAS28-MCP-1 (<2.2) was better than DAS28-ESR (<2.6) in indicating modified American Rheumatism Association remission and 2011 American College of Rheumatology/European League Against Rheumatism remission (75.61% vs. 36.99% and 81.71% vs. 49.13%, respectively) with odds ratios of 5.28 and 4.62 (both P < 0.001), respectively. We compared DAS28-MCP-1 with SDAI (≦3.3) in indicating remission with odds ratios of 2.63 (P = 0.002) and 0.98, respectively (and DAS28-MCP-1 with DAS28-CRP < 2.5: 1.33 and 0.92). Therefore, DAS28-MCP-1 is useful as an alternative in assessing RA activity.

Clinical Improvements as Predictors of Improvements in Patient-Reported Outcomes: Post Hoc Analysis of a Randomized, Open-Label Study of Etanercept in Latin American Patients with Rheumatoid Arthritis.

BackgroundIn rheumatoid arthritis (RA), little is known about clinical responses to treatment as predictors of patient-reported outcome (PRO) changes. In this post hoc analysis, we examined the relationship between clinical outcomes at week 12 and PRO changes at week 24 in patients with RA.MethodsIn an open-label study, Latin American patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX) were randomized to receive etanercept 50 mg/week plus MTX (ETN+MTX; n=281) or an additional conventional disease-modifying anti-rheumatic drug (DMARD) plus MTX (DMARD+MTX; n=142) for 24 weeks. The PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form (SF-36), Physician and Patient Global Assessment scores (PGA, PtGA), Physician and Patient Satisfaction, and an activity impairment assessment. PRO changes at week 24 were calculated by week-12 improvements using the American College of Rheumatology criteria (ACR <20, ≥20 to <50, ≥50 to <70, and ≥70) and the 28-joint Disease Activity Scores (DAS28 ≥3.2, ≥2.6 to <3.2, and <2.6). Observed-cases data were analyzed using an ANCOVA model with linear contrast, adjusted for baseline PRO and ACR/DAS28 values.ResultsFor both ETN+MTX- and DMARD+MTX-treated patients, there was a significant linear trend between week-12 changes in ACR and DAS28 responses and week-24 changes in HAQ-DI (P<0.001 for all), with numerical improvements generally favoring ETN+MTX. Similar relationships were observed for SF-36, PGA, PtGA, Physician Satisfaction, Patient Satisfaction, and activity impairment.ConclusionsIn patients with RA, clinical response after 12 weeks of treatment with ETN+MTX or DMARD+MTX could be a predictor of week-24 response for several PROs.Trial registrationClinicalTrials.gov, NCT00848354.

Changes in disability and their relationship with skin thickening, in diffuse and limited cutaneous systemic sclerosis: a retrospective cohort study

Objective: The burden of disability associated with systemic sclerosis (SSc) is being increasingly recognized. Our aim was to test the hypothesis that changes in functional ability over time differ between patients with limited (lcSSc) and diffuse cutaneous (dcSSc) subtypes, and that in dcSSc (but not lcSSc) these changes correlate with skin thickening.Method: This was a retrospective analysis of data collected prospectively between 2005 and 2016 at a single centre. Data recorded at annual review visits included modified Rodnan skin score (mRSS) and Health Assessment Questionnaire Disability Index (HAQ-DI). Yearly rates of mRSS and HAQ-DI change were assessed by individual linear regressions, and those gradients were compared between disease groups (lcSSc/dcSSc) for each of early/late disease (less/greater than 5 years’ duration).Results: The study included 402 patients (110 dcSSc, 292 lcSSc), with mean length of follow-up of 5.5 years (sd 3.5). Mean baseline HAQ-DI was 1.4 in dcSSc and 1.2 in lcSSc. In dcSSc, increased mRSS was associated with worsening disability (ρ = 0.36, p = 0.004) during early but not late disease (ρ = 0.12, p = 0.331). In lcSSc, changes in mRSS were not associated with changes in disability for early (ρ = −0.15, p = 0.173) or late disease (ρ = 0.10, p = 0.137).Conclusion: These findings confirm high disability in patients with SSc. A relationship between HAQ-DI and mRSS (worsening mRSS associated with increasing disability) was found only in patients with early dcSSc, suggesting that in other patient subgroups other factors play the major role.

Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study

ObjectivesInterleukin-6 (IL-6) is implicated in rheumatoid arthritis (RA) pathophysiology. Unlike IL-6 receptor inhibitors, sirukumab is a human monoclonal antibody that selectively binds to the IL-6 cytokine. The phase III, multicentre,...

Patient-reported Outcomes as Predictors of Change in Disease Activity and Disability in Early Rheumatoid Arthritis: Results from the Yorkshire Early Arthritis Register.

To assess patient-reported variables as predictors of change in disease activity and disability in early rheumatoid arthritis (RA). Cases were recruited to the Yorkshire Early Arthritis Register (YEAR) between 1997 and 2009 (n = 1415). Predictors of the 28-joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline and change over 12 months were identified using multilevel models. Baseline predictors were sex, age, symptom duration, autoantibody status, pain and fatigue visual analog scales (VAS), duration of early morning stiffness (EMS), DAS28, and HAQ-DI. Rates of change were slower in women than men: DAS28 fell by 0.19 and 0.17 units/month, and HAQ-DI by 0.028 and 0.023 units/month in men and women, respectively. Baseline pain and EMS had small effects on rates of change, whereas fatigue VAS was only associated with DAS28 and HAQ-DI at baseline. In patients recruited up to 2002, DAS28 reduced more quickly in those with greater pain at baseline (by 0.01 units/mo of DAS28 per cm pain VAS, p = 0.024); in patients recruited after 2002, the effect for pain was stronger (by 0.01 units/mo, p = 0.087). DAS28 reduction was greater with longer EMS. In both cohorts, fall in HAQ-DI (p = 0.006) was greater in patients with longer EMS duration, but pain and fatigue were not significant predictors of change in HAQ-DI. Patient-reported fatigue, pain, and stiffness at baseline are of limited value for the prediction of RA change in disease activity (DAS28) and activity limitation (HAQ-DI).

Efficacy and safety of tabalumab, an anti-B-cell-activating factor monoclonal antibody, in patients with rheumatoid arthritis who had an inadequate response to methotrexate therapy: results from a phase III multicentre, randomised, double-blind study

ObjectivesRandomised, double-blind, placebo-controlled study to evaluate efficacy and safety of tabalumab in patients with rheumatoid arthritis (RA) with inadequate responses to methotrexate (MTX-IR).Methods1041 patients with moderate–severe RA despite ongoing MTX...

Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis for Function and Pain is Affected by Rheumatoid Factor.

Objectives : To investigate differences in response to tumor necrosis factor inhibitor treatment (TNFi) in seropositive (rheumatoid factor positive; RF+) versus seronegative (RF-) patients with established RA as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain.Methods : RA patients from an established RA cohort were studied according to rheumatoid factor (RF) status for change in HAQ-DI and pain (0-3 VAS) one year after starting treatment with a TNFi.Results : There were 238 patients treated with TNFi who had follow-up data (178 RF+ and 60 RF-). Disease duration was longer in RF+ vs RF- (12+8 vs 8+8 years) but the proportion of females (82% vs 72%, P=0.7), baseline HAQ-DI (1.44+0.63 vs 1.41+0.63, P=0.8) and pain (1.92+0.67 vs 1.93+0.67, P=0.9) were not different. The mean duration of treatment of first TNFi was 2.8 vs 2.3 years, P=0.1 and 68% of RF+ vs 62% of RF- were still receiving first TNFi at last visit (P=0.5). For patients with data at baseline and one year, the one-year HAQ-DI change was significantly greater in 90 RF+ patients (-0.356) versus 38 RF- patients (-0.126; P=0.04). The mean pain improvement was also greater in 77 RF+ vs 32 RF- patients (-0.725 vs -0.332 respectively; P=0.03). Numbers are small, data are missing and comorbidities, DAS28 and anti-CCP were not collected.Conclusion : Despite limitations in the data, in established RA after failure of DMARDs, RF+ patients may be more responsive to TNFi therapy as measured by changes in HAQ-DI and pain.Innovation : There may be a better response to TNFi in RA if RF positive for function and pain.

Older age at rheumatoid arthritis onset and comorbidities correlate with less Health Assessment Questionnaire-Disability Index and Clinical Disease Activity Index response to etanercept in the RADIUS 2 registry.

Controversy exists in understanding the effects of age at onset and comorbidities in predicting rheumatoid arthritis (RA) response to biologic therapy. The objective of this study was to investigate the influence of age at onset and number of comorbidities on Health Assessment Questionnaire-Disability Index (HAQ-DI) and Clinical Disease Activity Index (CDAI) responses in active RA patients after 6 months of treatment with etanercept. One thousand eight hundred ninety-nine RA patients were assessed after 6 months of etanercept therapy. Patients met the following inclusion criteria: initiated etanercept, continued therapy for at least 6 months, and were not in CDAI low disease activity (LDA) at baseline (CDAI ≤10.0). Changes in HAQ-DI and CDAI scores over 6 months were analyzed across age of onset quintiles. Multivariate regression models evaluated the independent association between both age at onset and number of comorbidities with change in HAQ-DI/CDAI scores or achieving LDA, while accounting for other covariates. Significant improvements in HAQ-DI and CDAI scores were observed in all age-onset groups, although HAQ-DI improvements were less in older-onset patients. Results of multiple linear regression demonstrated that younger age at onset, higher baseline HAQ-DI/CDAI score, rheumatoid factor positivity, shorter disease duration, and fewer comorbidities at baseline were independently associated with improvement in both HAQ-DI and CDAI scores. Similarly, achieving CDAI LDA after 6 or more months of etanercept was associated with younger age at onset, higher baseline CDAI, shorter disease duration, and fewer comorbidities. These patients with older-onset RA and more comorbidities clinically improved with etanercept, but had lower odds of achieving CDAI LDA. Age of onset and number of comorbidities may be important in determining RA tumor necrosis factor inhibitor response.

Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

ObjectiveAssess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents.MethodsIn...

THU0257 Investigation of parameters of oral aperture in 131 patients with systemic sclerosis in a three-year single-centre prospective study

BackgroundDecreased ability of mouth opening has a remarkable impact on oral hygiene, nutrition and quality of life in systemic sclerosis (SSc).ObjectivesTo evaluate different parameters of oral aperture in a large...

Disability outcomes and dose escalation with etanercept, adalimumab, and infliximab in rheumatoid arthritis patients: a US-based retrospective comparative effectiveness study

Introduction:Rheumatoid arthritis (RA) is a chronic disease that if left untreated may substantially impair physical functioning. Etanercept, infliximab, and adalimumab are tumor necrosis factor (TNF) blockers whose FDA-approved indications in the US include moderate to severe RA. TNF-blocker dose escalation has been well documented in the literature; however, the comparative effectiveness of these agents remains uncertain.Objective:To compare the effectiveness and dose escalation rates of etanercept, adalimumab, and infliximab in US community settings. We hypothesized that etanercept would be equivalent to infliximab and adalimumab in patient-reported disability 9–15 months after therapy initiation, and that fewer etanercept patients would experience dose escalation.Methods:This is a retrospective analysis of the Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS). Adult patients with no biologic use 6 months before TNF-blocker initiation (index) and with Health Assessment Questionnaire Disability Index (HAQ-DI) scores at index and 9–15 months after index were analyzed (218 etanercept, 93 infliximab, and 40 adalimumab).Results:HAQ-DI change scores at 9–15 months did not differ by treatment (−0.12, −0.10, and −0.08 points for etanercept, infliximab, and adalimumab, respectively; p = 0.52). Dose increases were observed in 1.4% of etanercept, 10.8% of infliximab (p < 0.001), and 12.5% of adalimumab patients (p = 0.004). HAQ-DI change was associated with pre-index HAQ-DI score (p < 0.0001) and disease duration (p = 0.001).Conclusions:Fewer etanercept patients escalated dose than infliximab or adalimumab patients, but improvements in functional disability were similar. These differences may have been influenced by package labeling, mode of administration, or other factors. RA treatment with infliximab and adalimumab in community settings, characterized by dose escalation, did not yield greater disability improvements compared to etanercept, which remained at a relatively stable dose. Uncontrolled treatment selection in this observational design may have influenced outcomes, and prior methotrexate treatment may partly explain disability improvements smaller than typically observed in clinical trials.

Analysis of the Validation Status of Quality of Life and Functional Disability Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis: Results of a Systematic Literature Analysis by the Expert Panel on Outcomes Measures in Pulmonary Arterial Hypertension Related to Systemic Sclerosis (EPOSS)

We aimed to assess the current validity status of the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the 36-item Medical Outcomes Study Short Form Health Survey (SF-36). Studies using HAQ-DI and/or SF-36 in patients with pulmonary arterial hypertension (PAH) associated with systemic sclerosis (PAH-SSc) were identified through a systematic literature review and assessed according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus group criteria. Both HAQ-DI and SF-36 were considered credible (having face validity) and feasible. Based on expert opinion, neither HAQ-DI nor SF-36 was specific for PAH-SSc since their results may be influenced by other aspects of SSc (judged "unclear" with respect to the content validity criterion). In the overall SSc population, there was significant albeit weak correlation between physical component SF-36 scores and pulmonary artery systolic pressure (PASP) by echocardiography (Kendall tau b = -0.2, p < 0.01). Although HAQ-DI also correlated with PASP by echocardiography, there were no significant correlations in SSc patients with PAH proven by right heart catheterization between changes in HAQ-DI over time and changes in other PAH measures including 6-min walk distance (r = -0.04, p = 0.86), expert global assessment (r = 0.06, p = 0.97), and New York Heart Association functional class (r = 0.38, p = 0.39), indicating lack of construct validity for HAQ-DI in PAH-SSc. No studies enabling assessment of criterion validity or discrimination of HAQ-DI or SF-36 in PAH-SSc could be identified. Further validation of HAQ and SF-36 in PAH-SSc is needed. Alternatively, more specific assessments for functional disability or quality of life in PAH-SSc might be required.

Minimally Important Difference of Health Assessment Questionnaire in Psoriatic Arthritis: Relating Thresholds of Improvement in Functional Ability to Patient-rated Importance and Satisfaction

To evaluate changes in function as measured by Health Assessment Questionnaire Disability Index (HAQ-DI) and the meaningfulness of the changes, in importance and satisfaction, in patients with psoriatic arthritis (PsA). HAQ-DI was assessed at baseline and at Weeks 4, 12, and 24 in a randomized double-blind study of 205 patients with active PsA receiving etanercept 25 mg twice weekly or placebo. Concurrently, patients rated the importance of and satisfaction with their change in function on a 7-point scale (1 = not at all important/satisfied; 7 = extremely important/satisfied). Mean HAQ-DI improvement corresponding to ratings of minimally (2-3) or very (6-7) important or satisfied was determined using a posthoc linear mixed-model analysis. Patient importance ratings were used as an anchor to estimate minimally important difference (MID) for HAQ-DI; distribution-based estimates were also calculated. A total of 161 patients (69 placebo; 92 etanercept) had ≥ 1 HAQ-DI scores showing improvement from baseline and a corresponding importance or satisfaction rating. HAQ-DI improvements corresponding to importance scale ratings of 2 or 3 were 0.335 (95% CI 0.214, 0.455) and 0.360 (95% CI 0.263, 0.456), respectively, suggesting an MID of about 0.35. HAQ-DI improvements corresponding to satisfaction scale ratings of 2 and 3 were 0.293 (95% CI 0.230, 0.357) and 0.360 (95% CI 0.307, 0.413). For a given change in HAQ-DI, nearly two-thirds of patients indicated a lower rating for satisfaction than for importance. This trial was registered in the ClinicalTrials.gov registry (NCT00317499). Our study suggests the MID for HAQ-DI in PsA is about 0.35. The results may also provide insight into patient satisfaction with changes in function and expectations for therapy.