Five-year follow-up of patients with difficult-to-treat rheumatoid arthritis.

OBJECTIVES: To elucidate the long-term outcomes of patients with difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: We collected data on the clinical course of patients who had been identified as D2T RA in 2018 until 2023. We stratified the patients according to outcomes at the last visit: resolved D2T RA, persistent D2T RA, and mortality. We compared their clinical characteristics and investigated the predictive factors for the resolution of D2T RA or mortality. Furthermore, we investigated the impact of the causes of D2T RA identified in 2018, multidrug resistance, comorbidities, and socioeconomic factors on outcomes in 2023. RESULTS: Of 173 patients identified as D2T RA in 2018, 150 were included in the analysis. Among them, D2T RA was resolved in 67 (45%), 75 (50%) remained as D2T RA, and 8 (5%) died. Patients with resolved D2T RA were significantly younger at the latest visit (p= 0.02), had a higher proportion of treatment changes during five years (p= 0.002), and had a higher proportion of interleukin-6 receptor inhibitors use in 2023 (p= 0.04) than those in patients with persistent D2T RA or those who died. D2T RA resolved in 38% of patients with multidrug resistance, mainly with treatment changes. Rheumatic disease comorbidity index and glucocorticoid dose escalation were independent risk factors for mortality (odds ratio [OR], 3.50; p= 0.02 and OR, 31.9; p= 0.002, respectively). CONCLUSION: Further modifications in RA treatment are useful for resolving D2T RA. Multiple comorbidities and glucocorticoid use are associated with mortality.

Pain is Common in Myositis and Associated with Disease Activity.

BACKGROUND: Understanding pain in myositis remains challenging. This study aimed to assess patient-reported pain and its correlation with myositis core set measures (CSMs), patient-reported outcomes (PROs), and functional measures. METHODS: Fifty subjects underwent baseline, 3-month, and 6-month assessments, evaluating myositis CSMs, functional measures, and patient-reported outcomes. Pain was measured using three methods: (1) a 10-cm Visual Analogue Scale (VAS), (2) pain score from the HAQ-DI, and (3) SF-36 (Short Form survey) pain questions. Correlations between disease activity measures and pain were examined at baseline, and changes in both were assessed at 6 months, along with longitudinal change of pain. The change in pain was also correlated with the published 2016 ACR/EULAR myositis response criteria, physician/patient's assessment of change. RESULTS: Nearly half of patients (45%) reported moderate to severe pain in all 3 pain scales, with higher severity of pain in PM/NM subset. At baseline, pain severity showed a strong correlation with most CSMs, PROs and functional outcomes in all the 3 pain scales and similar trends were noted for change in pain at the 6 months. On longitudinal analysis, the physical function scores and fatigue showed strong correlation with pain. Pain improved in myositis patients with improvement in disease activity over time. CONCLUSIONS: Pain is common in myositis and is associated with multiple measures of disease activity, PROs, and functional outcomes in myositis. Most importantly pain improves with improvement in disease activity. SF-36 pain questions have good psychometric properties.

The Extent and Nature of Functional Limitations According to the Health Assessment Questionnaire Disability Index in Patients with Rheumatoid Arthritis and Severe Functional Disability.

BACKGROUND: For a subgroup of people with rheumatoid arthritis (RA) and severe disability, insight into their limitations is crucial for adequate treatment. AIM: To describe the extent and nature of functional limitations in people with RA and severe disability and to explore the associations of the extent of the functional limitations with patient characteristics, disease characteristics, and outcome measures. METHODS: Baseline data of 215 participants in an RCT on the (cost-)effectiveness of longstanding physiotherapy were used. Functional limitations were assessed with the Health Assessment Questionnaire Disability Index (HAQ-DI). The total HAQ-DI including eight domain scores were calculated. Associations between high HAQ-DI scores (≥2, yes/no) and other variables were examined using the Student's t-test or Chi-squared test where appropriate. RESULTS: The participants (90% women, age 58.8 ± 12.8 years) had a mean HAQ-DI score of 1.7 ± 0.5. The majority (56%) showed a moderate-to-severe disability in all domains. Higher HAQ-DI scores seemed to be associated with advanced age, longer disease duration, unemployment, joint replacements, and outcomes for daily functioning and physical quality of life, but not with measures of disease activity. CONCLUSIONS: Our findings indicate that a comprehensive assessment of all areas of daily activities in this subgroup is necessary in order to provide appropriate (non-)pharmacological care.

Assessment of Disease Activity, Structural Damage, and Function in Rheumatoid Arthritis.

The primary goal in the treatment of rheumatoid arthritis (RA) is to control disease activity, prevent structural damage in joints, and normalize function. Therefore, reliable tools are needed to disease activity, physical function, and radiographic progression in RA. We herein describe methods recently used to assess RA.

Mapping health assessment questionnaire disability index onto EQ-5D-5L in China.

Objective: This research aimed to develop the more accurate mapping algorithms from health assessment questionnaire disability index (HAQ-DI) onto EQ-5D-5L based on Chinese Rheumatoid Arthritis patients. Methods: The cross-sectional data of Chinese RA patients from 8 tertiary hospitals across four provincial capitals was used for constructing the mapping algorithms. Direct mapping using Ordinary least squares regression (OLS), the general linear regression model (GLM), MM-estimator model (MM), Tobit regression model (Tobit), Beta regression model (Beta) and the adjusted limited dependent variable mixture model (ALDVMM) and response mapping using Multivariate Ordered Probit regression model (MV-Probit) were carried out. HAQ-DI score, age, gender, BMI, DAS28-ESR and PtAAP were included as the explanatory variables. The bootstrap was used for validation of mapping algorithms. The average ranking of mean absolute error (MAE), root mean square error (RMSE), adjusted R 2 (adjR 2) and concordance correlation coefficient (CCC) were used to assess the predictive ability of the mapping algorithms. Results: According to the average ranking of MAE, RMSE, adjR 2, and CCC, the mapping algorithm based on Beta performed the best. The mapping algorithm would perform better as the number of variables increasing. Conclusion: The mapping algorithms provided in this research can help researchers to obtain the health utility values more accurately. Researchers can choose the mapping algorithms under different combinations of variables based on the actual data.

Factors Leading to Diagnostic and Therapeutic Delay of Rheumatoid Arthritis and Their Impact on Disease Outcome.

Objective To identify the factors which lead to delay in diagnosis and initiation of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients and their impact on disease outcome and functional ability. Methodology This cross-sectional study was conducted from June 2021 to May 2022 at the Department of Rheumatology and Immunology, Sheikh Zayed Hospital, Lahore. Inclusion criteria were patients aged >18 years who were diagnosed with RA, based on American College of Rheumatology (ACR) criteria 2010. Delay was defined as any sort of delay which leads to delay in diagnosis or initiation of treatment of more than three months. The factors and impact on disease outcome were measured by using Disease Activity Score-28 (DAS-28) for disease activity and Health Assessment Questionnaire-Disability Index (HAQ-DI) for functional disability. The collected data were analyzed with Statistical Package for Social Sciences (SPSS) version 24 (IBM Corp., Armonk, NY, USA). Results One hundred and twenty patients were included in the study. Mean delay in referral to a rheumatologist was 36.75±61.07 weeks. Fifty-eight (48.3%) patients with RA were misdiagnosed before presentation to a rheumatologist. Sixty-six (55%) patients had the perception that RA is a non-treatable disease. Delay in diagnosis of RA from onset of symptoms (lag 3) and delay in start of DMARDs from onset of symptoms (lag 4) were significantly associated with increased DAS-28 and HAQ-DI scores (p-value 0.001). Conclusion The factors which led to diagnostic and therapeutic delay were delayed consultation with a rheumatologist, old age, low education status and low socioeconomic status. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies had no role in diagnostic and therapeutic delay. Many RA patients were misdiagnosed with gouty arthritis and undifferentiated arthritis before consulting a rheumatologist. This diagnostic and therapeutic delay compromises RA management leading to high DAS-28 and HAQ-DI in RA patients.

Functional disability and health-related quality of life among systemic sclerosis patients in Bangladesh.

OBJECTIVE: To assess the relationship between functional disability and health-related quality of life (HRQoL) among systemic sclerosis (SSc) patients. METHODOLOGY: This cross-sectional study was carried out on 78 adults who met the classification criteria for SSc defined by the American College of Rheumatology/European League of Rheumatology (ACR/EULAR)-2013. The Bangla version of Short Form 36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were used to measure HRQoL and functional disability in SSc patients. RESULTS: The patients' median [IQR] HAQ-DI was 1.4 [0.6-2.1], with 37.2% having a mild functional disability, 33.3 percent having a moderate functional disability, and 29.5 percent having a severe functional disability. The hygiene and activity domains of the HAQ-DI obtained the highest scores, 2.0 [0.0-3.0] and 2.0 [1.0-3.0], respectively. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36 had median [IQR] values of 26.2 [15.0-58.1] and 42.0 [19.6-60.6]. The highest score was 50.0 [25.0-75.0] in social functioning. The PCS of the SF-36 was moderately correlated with the HAQ-DI (rs = - 0.629, P < 0.001) and the MCS of the SF-36 was weakly correlated with the HAQ-DI ((rs = - 0.344, P < 0.001). Age, female sex, and incomplete fist closure substantially influenced functional status. Calcinosis, Raynaud's Phenomenon, and flexion contracture significantly diminished the quality of life. CONCLUSIONS: Functional disability negatively affects health-related quality of life. Age, Musculoskeletal, and skin involvement are significantly associated with poor quality of life and functional disability. Therefore, treatment strategies should be aimed at reducing functional disability, which will enhance the HRQoL of SSc patients.

Driving Impairment and Healthcare Provider Counseling in Rheumatoid Arthritis and Osteoarthritis Patients: A Cross-Sectional Survey.

BACKGROUND/OBJECTIVE: To examine rates of counseling on driving for individuals with osteoarthritis (OA) and/or rheumatoid arthritis (RA) and evaluate the Health Assessment Questionnaire Disability Index (HAQ-DI) as a screening tool for further driving evaluation. METHODS: A cross-sectional survey was completed by individuals recruited via ResearchMatch (a national web-based recruitment tool) between March 5 and April 20, 2020. Individuals with a current US driver's license, ≥18 years old, with self-reported OA and/or RA diagnosis were surveyed about driving difficulty and vehicle modification and completed a HAQ-DI assessment. Respondents were dichotomized based on reporting vehicle modification(s) due to arthritis versus no modification(s) for univariate and multivariate analyses. RESULTS: Of 4,435 recruited patients, 304 (6.9%) met inclusion/exclusion criteria and completed the surveys. Of all respondents, 259 (85.2%) reported at least some difficulty with one or more driving activities, but only 47 (15.5%) reported discussion with a physician and/or healthcare professional. A total of 184 (60.5%) respondents had HAQ-DI ≥ 1 and were more likely to report vehicle modification(s) compared to respondents with HAQ-DI score < 1 (OR = 5.00, 95% CI = 2.69-9.32, p < 0.011) after controlling for age, gender, type of arthritis, and driving behaviors. CONCLUSION: Few respondents report discussion of driving difficulties with healthcare providers, although many report driving-related impairments, particularly those with HAQ-DI scores ≥ 1. Our data suggest a strong association between HAQ-DI scores and vehicle modification. The HAQ-DI may serve as a screening tool to predict a patient's need for driving evaluation and vehicle modification(s).

The Impact of Metabolic Syndrome on Quality of Life Among Individuals With Knee Osteoarthritis Living in Egypt.

Background: Several studies have linked metabolic syndrome (MetS) to osteoarthritis (OA), but they have not looked into how MetS can affect the health-related quality of life (HRQOL) of OA individuals. Objectives: We aimed to assess the association of MetS and its components, including obesity, hypertension, hyperglycemia, and dyslipidemia, with HRQOL among Egyptians with knee OA. Methods: This cross-sectional study comprised 116 adult Egyptian participants with knee OA. They were divided into 2 groups based on whether or not they had the MetS. All participants were subjected to a thorough medical history taking and a detailed medical examination. The Kellgren and Lawrence (K/L) scale evaluated OA in all individuals using anteroposterior knee radiographs. The Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to assess participants' HRQOL; their higher scores indicate more disability. Spearman rank and Pearson's correlation analyses were used to assess the association between variables. Results: Diabetes, hypertension, dyslipidemia, and obesity were significantly associated with the OA + MetS group with a prevalence of 77.6%, 82.8%, 77.6%, and 50.0%, respectively. According to the K/L scale, 70.7% of the OA + MetS group had grade IV knee affection. The HAQ-DI and WOMAC scores were significantly (P < .001) higher among the OA + MetS individuals compared with the OA individuals. Interleukin (IL)-6 serum levels were also significantly higher in the OA + MetS group (P = .036) and increased significantly with the more serious radiological damage and functional disability. We found significant positive correlations between HAQ-DI and WOMAC with waist circumference (P = .004, .001), as well as triglycerides (P = .006, .008), cholesterol (P = .041, .048), fasting blood sugar (P < .001, < .001) and significant negative correlations with high-density lipoprotein levels (P = .628, .002). Conclusions: Individuals with knee OA with MetS showed more significant radiological damage, severe functional disability, and poor HRQOL. They also had higher levels of IL-6, which correlated significantly with the degree of disability, promoting it as a significant therapeutic target.

The impact of filgotinib on patient-reported outcomes and health-related quality of life for patients with active rheumatoid arthritis: a post hoc analysis of Phase 3 studies.

BACKGROUND: The effects of filgotinib on patient-reported outcomes (PROs) from 3 trials in patients with active rheumatoid arthritis were investigated. METHODS: Methotrexate (MTX)-naïve patients received filgotinib 200 or 100 mg plus MTX (FIL200+MTX, FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX monotherapy through 52 weeks (NCT02886728). Patients with inadequate response (IR) to MTX (MTX-IR) received FIL200+MTX, FIL100+MTX, adalimumab 40 mg +MTX (ADA+MTX), or placebo (PBO)+MTX (rerandomized to FIL200+MTX or FIL100+MTX at week 24) through 52 weeks (NCT02889796). Patients with IR to biologic disease-modifying antirheumatic drugs (bDMARD-IR) received FIL200 or FIL100 or PBO with background stable conventional synthetic (cs) DMARDs for up to 24 weeks (NCT02873936). PROs included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical/mental component summary (PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and Patient Global Assessment of Disease Activity (PtGA). Data are reported as least-squares mean changes from baseline with standard error to the timepoint representing each study's primary endpoint. All statistical comparisons are of filgotinib groups vs their respective control groups. RESULTS: At week 24, among MTX-naïve patients, change from baseline (standard deviation) in HAQ-DI was - 1.00 (0.03; P < 0.001) with FIL200+MTX, - 0.94 (0.04; P < 0.01) with FIL100+MTX, and - 0.91 (0.04; P < 0.05) with FIL200 alone compared with - 0.81 (0.03) with MTX alone. At week 12, among MTX-IR patients, change from baseline in HAQ-DI was - 0.69 (0.04; P < 0.001 vs PBO+MTX, P < 0.05 vs ADA) with FIL200+MTX, - 0.57 (0.04; P < 0.001 vs placebo) with FIL100+MTX, and - 0.60 (0.04) with ADA vs - 0.40 (0.04) with PBO+MTX. At week 12, among bDMARD-IR patients, change from baseline in HAQ-DI was - 0.50 (0.06; P < 0.001) with FIL200+csDMARD and - 0.46 (0.05; P < 0.001) with FIL100+csDMARD vs - 0.19 (0.06) with placebo+csDMARD. Changes in SF-36 PCS and MCS, FACIT-Fatigue, WPAI, and PtGA tended to favor filgotinib over PBO, MTX, and ADA. Greater proportions of patients experienced clinically meaningful differences with either dosage of FIL in combination with csDMARDs (including MTX) and with FIL200 monotherapy vs comparators. CONCLUSIONS: Filgotinib provided improvements in PROs across patient populations. These findings suggest filgotinib can be an effective treatment option for patients with insufficient response to MTX or bDMARDs and patients who are MTX-naïve. TRIAL REGISTRATION: ClinicalTrials.gov , FINCH 1, NCT02889796 , first posted September 7, 2016; FINCH 2, NCT02873936 , first posted August 22, 2016, retrospectively registered; FINCH 3, NCT02886728 , first posted September 1, 2016, retrospectively registered.

Anxiety, Distress, and Depression in Elderly Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) and affective disorders (anxiety/depression) constitute important pathologies in the elderly population, and their coexistence creates synergistically increased problems in functional ability and quality of life of the patients. Purpose: Evaluation of anxiety, distress, and depression in elderly (≥65 years old) patients with RA. Patients ­ methods: 114 patients from the cities of Patras, Arta and Ioannina (all located in Western Greece) were included. Demographics and medical information regarding RA were recorded, including disease duration, medication, previous treatments, disease activity measures, comorbidities etc. Patients answered the State-Trait Anxiety Inventory (STAI), General Health Questionnaire-28 (GHQ28) and Health Assessment Questionnaire -Disability Index (HAQ-DI) questionnaires, for evaluation of anxiety, general health and functional ability, respectively. Statistical analysis was made by using STATA. Results: 88 women (78.07%) and 25 men (21.93%) with median age 70 years and median disease duration 10 years were studied. Female patients, with longer disease duration and higher disease activity, had statistically significant higher levels of anxiety, worse general health and decreased functional ability. A strongly significant association was found between the levels of anxiety and distress, with disease activity and functional inability. Conclusions: Levels of anxiety and distress are strongly associated with disease activity and functional inability in elderly patients with RA. Women with longer disease have higher levels of anxiety and distress. Controlling disease activity is of upmost importance for improvement of anxiety and distress and functional ability. Larger studies are needed for evaluation of anxiety and distress in elderly patients with RA.

Patient- and physician-reported outcomes from two phase 3 randomized studies (RAJ3 and RAJ4) of peficitinib (ASP015K) in Asian patients with rheumatoid arthritis.

BACKGROUND: Peficitinib (ASP015K), a novel oral Janus kinase inhibitor, has demonstrated efficacy and safety in the treatment of patients with rheumatoid arthritis (RA). This study evaluated the effect of peficitinib on patient- and physician-reported outcomes in Asian patients with RA and an inadequate response to prior disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients from two randomized, placebo-controlled, double-blind, phase 3 trials (RAJ3 and RAJ4) received once-daily peficitinib 100 mg, peficitinib 150 mg, or placebo, alone or in combination with DMARDs (RAJ3), or in combination with methotrexate (RAJ4). Mean changes in Work Productivity and Activity Impairment (WPAI) questionnaire domain scores from baseline, and percentages of patients achieving minimal clinically important differences (MCIDs) for patient- and physician-reported outcomes (WPAI, Health Assessment Questionnaire - Disability Index [HAQ-DI], and Subject's Global Assessment of Pain [SGAP]), and Physician's Global Assessment of disease activity (PGA) were evaluated at weeks 4, 8, 12, and 12/early termination (ET). RESULTS: Data from 1025 patients were analyzed. At week 12/ET in both studies, patients who received peficitinib 100 mg or 150 mg reported significantly improved WPAI domain scores from baseline (except for absenteeism in RAJ4) compared with placebo (both doses, p<0.05). A higher proportion of peficitinib- versus placebo-treated patients achieved MCID in WPAI, HAQ-DI, SGAP, and PGA in studies RAJ3 and RAJ4. Significant differences with peficitinib versus placebo were evident in both studies as early as week 4 in HAQ-DI (peficitinib 150 mg only), SGAP, and PGA, and week 8 in WPAI loss of work productivity and daily activity impairment. At week 12/ET, significantly higher proportions of patients receiving peficitinib versus placebo achieved MCID in HAQ-DI, SGAP, PGA, and WPAI domains of presenteeism (RAJ3 only), loss of work productivity (RAJ3 only), and daily activity impairment (p<0.05 for all comparisons). CONCLUSIONS: Peficitinib 100 mg or 150 mg administered daily over 12 weeks resulted in clinically meaningful improvements in outcomes that are important to RA patients, including pain, physical function, and work productivity and activity. These observations were reinforced through similar improvements in physicians' rating of disease activity. TRIAL REGISTRATION: RAJ3: ClinicalTrials.gov, NCT02308163 , registered 4 December 2014. RAJ4: ClinicalTrials.gov, NCT02305849 , registered 3 December 2014.

Evaluation of levels of oxidative stress as a potential biomarker in patients with rheumatoid arthritis.

OBJECTIVES: One of the most prevalent autoimmune disease globally, rheumatoid arthritis (RA) is caused by interplay of multiple inflammatory mediators in specific joints. Altered redox balance is one of the key factors in pathophysiology of RA. This study aims to find whether oxidative stress in peripheral blood neutrophil correlates with the disease activity and disability associated with it. METHODS: Ten healthy controls and 29 RA patients with moderate to severe disease activity (DAS28 score >3.2) were recruited and reactive oxygen species (ROS) level in peripheral blood neutrophil was measured using flow cytometry at baseline visit and after 6 months follow-up. Functional status of RA patients was measured using Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: RA patients showed significantly higher level of ROS in compared to healthy control. DAS28 correlated well with ROS at baseline visit (Pearson's r = +0.63) as well as follow-up visit (Pearson's r = +0.75). HAQ-DI showed weak positive correlation at baseline visit (Pearson's r = 0.1) but it was negative at follow-up visit (Pearson's r = -0.19). CONCLUSIONS: Oxidative stress mirrors the disease activity in RA and can be considered as a biomarker, but it is not related with functional ability of the patients.

Musculoskeletal health and capability wellbeing: Associations between the HAQ-DI, ICECAP-A and ICECAP-O measures in a population survey.

BACKGROUND: The capability approach has received increasing attention in wellbeing measurement in the past years, but it has still remained an underexplored area in musculoskeletal (MSK) health. OBJECTIVE: We aimed to explore the capability wellbeing in relation to MSK health, by measuring the associations between the Health Assessment Questionnaire Disability Index (HAQ-DI) physical functioning and the ICECAP-A and ICECAP-O capability wellbeing measures. DESIGN: A cross-sectional survey was performed in 2019 on a representative sample of the Hungarian general adult population. METHOD: Capability wellbeing was measured by the ICECAP-A (age-group 18-64) and ICECAP-O (age group 65+) questionnaires. MSK health was defined by the HAQ-DI, the mobility domain of the EQ-5D-3L/-5L health status measures, self-reported walking problems and MSK diagnosis (neck/back/low back defects, hip/knee arthrosis, osteoporosis). RESULTS: Altogether 2021 individuals (female: 50.1%) participated in the survey with mean (SD) age of 48.7 (17.9) years and HAQ-DI of 0.138 (0.390). ICECAP-A (N = 1568, 77.6%) and ICECAP-O (N = 453, 22.4%) scores were on average (SD) 0.894 (0.126) and 0.828 (0.150), respectively. Spearman correlations between the HAQ-DI and ICECAP-A/-O index scores were moderate (r = -0.303 and -0.496; p < 0.05). Both the ICECAP-A/-O index scores differed significantly (ANOVA test, p < 0.05) across all MSK subgroups. In the ordinary least square regressions, marginal effects of ICECAP-A/-O scores on HAQ-DI were significant (-0.149 and -0.123) when controlling for socio-demographic characteristics. CONCLUSIONS: MSK health problems are associated with lower capability wellbeing. ICECAP-A/-O might capture effects of MSK conditions not measured by the HAQ-DI or the EQ-5D-5L. Further studies should test these associations in disease-specific samples.

Diagnostic and therapeutic delay in Rheumatoid Arthritis patients: Impact on disease outcome.

OBJECTIVE: To identify factors causing diagnostic and therapeutic delay in patients with rheumatoid arthritis, and to evaluate relationship of diagnostic and therapeutic delay with disease outcome. METHODS: This cross-sectional study was conducted in Rheumatology Department, Fatima Memorial Hospital, Lahore, Pakistan, from May 2018 to July 2018. In this study 102 patients fulfilling ACR/EULAR criteria 2010 were enrolled. Lag times were calculated in months: lag-1 (delay in initial medical consultation); lag-2 (delay in consulting rheumatologists); lag-3 (diagnostic delay); lag-4 (therapeutic delay). Disease activity and functional outcome were measured by DAS28, HAQ-DI respectively. Association of lag-3 and lag-4 with HAQ-DI and DAS28 was calculated by Pearson correlation. RESULTS: Median (IQR) disease duration of study group was 6(2-10) years. Initial consultations were with; orthopedic surgeon 40(39.2%), general practitioner 27(26.5%), rheumatologist 13(12.7%), medical specialists 14(13.7%). Median (IQR) lag times in months: lag-1 (delayed initial consultation): 2(0-5), lag-2 (delay in consulting rheumatologist): 30(7.7-72), lag-3 (diagnostic delay): 12(3-48), lag-4 (therapeutic delay):18(5.7-72). Factors attributed to lag-3 (diagnostic delay) and lag-4 (therapeutic delay) (p<0.05): older Age (r= 0.2), education level(r= - 0.2), initial consultation (non-rheumatologist) (r=0.2), lag-2(r=0.8), >three doctors visited before diagnosis(r=0.6). Positive anti-CCP antibodies(r=0.2) and lag-1 (delayed initial consultation) (r=1) were associated with lag-3 (diagnostic delay) only; no association was found with positive RA factor. Significant correlation (p=<0.05) of lag-3 (diagnostic delay) was found with both DAS28(r=0.2) & HAQ-DI(r=0.2). Similarly lag-4 (therapeutic delay) also correlated with both & DAS28(r=0.2) & HAQ-DI(r=0.3) (p=<0.05). CONCLUSION: Diagnostic and therapeutic delay were associated with older age, lower education and delayed consultation with rheumatologist but not with positive RA factor. Positive anti-CCP antibodies were associated with diagnostic delay only. Diagnostic and therapeutic delay led to high disease activity and poor functional outcome in RA patients.

Yoga improves mitochondrial health and reduces severity of autoimmune inflammatory arthritis: A randomized controlled trial.

BACKGROUND: Oxidative stress (OS) and mitochondrial alterations have been implicated in the pathogenesis of rheumatoid arthritis (RA). Various environmental triggers like air pollutants, smoking, unhealthy social habits and sedentary lifestyle induce OS, which may compromise mitochondrial integrity. This trial was designed to explore the effect of 8-weeks yoga practice on mitochondrial health and disease severity in an active RA group compared with a usual-care control group. METHODS: A total of 70 subjects were randomized into two groups: yoga group and non-yoga group. Mitochondrial health was assessed by calculation of mitochondrial DNA copy number (mtDNA-CN), OS markers, mitochondrial activity, mitochondrial membrane potential (ΔΨm), circadian rhythm markers and transcripts associated with mitochondrial integrity: AMPK, TIMP-1, KLOTHO, SIRT-1, and TFAM. Parameters of disease activity and disability quotient were also assessed by disease activity score - erythrocyte sedimentation rate (DAS28-ESR) and health assessment questionnaire-disability index (HAQ-DI), respectively. RESULTS: In yoga group, there was a significant upregulation of mtDNA-CN, mitochondrial activity markers, ΔΨm, and transcripts that maintain mitochondrial integrity after 8-weeks of yoga. There was optimization of OS markers, and circadian rhythm markers post 8-weeks practice of yoga. Yoga group participants showed significant improvements in DAS28-ESR (p < 0.05) and HAQ-DI (p < 0.05) over the non-yoga group. CONCLUSION: Adoption of yoga by RA patients holds the key to enhance mitochondrial health, improve circadian rhythm markers, OS marker regulation, upregulation of transcripts that maintain mitochondrial integrity, reduce disease activity and its associated consequences on health outcome and hence can be beneficial as an adjunct therapy.

Improvement from ixekizumab treatment in patients with psoriatic arthritis who have had an inadequate response to one or two TNF inhibitors.

OBJECTIVE: To evaluate the efficacy of ixekizumab (IXE), a monoclonal antibody selectively targeting interleukin-17A, in patients with inadequate response to one or two TNF inhibitors (TNFi). METHODS: A phase 3 study (SPIRIT-P2; NCT02349295) randomized patients with PsA with inadequate response or intolerance to one or two TNFi to receive 80-mg IXE every 2 weeks (n = 123) or every 4 weeks (n = 122) after a 160-mg starting dose or placebo (PBO; n = 118) through week 24. This post hoc analysis used data from inadequate responders to one or two TNFi, measuring the percentage achieving: ≥50% improvement in ACR response criteria (ACR50) and 100% improvement from baseline in the Psoriasis Area and Severity Index (PASI 100), ACR50, improvement in HAQ-Disability Index (HAQ-DI) ≥0.35, minimal disease activity (MDA), European League Against Rheumatism (EULAR) Good Response Criteria [improvement in Disease Activity Score 28 CRP (DAS28-CRP) >1.2], and Disease Activity in PsA (DAPSA) ≤14. RESULTS: There were no significant differences in baseline characteristics between inadequate responders to one and two TNFi. At week 24, significantly more patients irrespective of previous TNFi experience receiving IXE than PBO achieved ACR50, HAQ-DI ≥0.35 improvement, MDA, EULAR good response, and DAPSA ≤14, and significantly more patients with inadequate response to one TNFi receiving IXE than PBO achieved ACR50 and PASI 100. Improvement persisted in all measures through week 52. CONCLUSION: IXE improved the signs and symptoms of PsA in a population of difficult-to-treat patients with inadequate response to one or two TNFi.

Clinicodemographic Profiles of Rheumatoid Arthritis Patients from a Single Center in Saudi Arabia.

PURPOSE: Rheumatoid arthritis (RA), if left untreated, can lead to joint damage and deformity, disability, and even death. Hence, early diagnosis and management are essential to improve clinical and functional outcomes. This study aimed to identify the most common variables and risk factors related to RA activity among patients living in the Kingdom of Saudi Arabia (KSA). PATIENTS AND METHODS: This study was conducted between January 2018 and March 2019 on consecutive patients diagnosed with RA at a tertiary care hospital in KSA. Adult patients (≥18 years old) diagnosed with RA based on the American College of Rheumatology 2010 criteria were recruited. The Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) and health assessment questionnaire disability index (HAQ-DI) were calculated for 75 patients attending the rheumatology clinic during the study period to evaluate the rate of remission and functional capacity, and to compare findings with other local studies after assessing the relationship of these factors with medication use and existing comorbidities. RESULTS: The majority of the 75 patients were female (n=64), with a mean age of 49.7 years and average disease duration of 130 days. The median HAQ-DI was less than 0.5 (range 0-1.95). The DAS28-CRP scores revealed moderate disease activity in 45.3% and low disease or remission in 38.6% of the patients. Many patients (45.3%) were treated with methotrexate, and the most commonly used biological treatment was adalimumab in 14.6%. Comorbidities included hypertension (26.7%) and diabetes mellitus (18.7%). There was a strong association between cardiovascular diseases and a high DAS28-CRP score (p < 0.001). CONCLUSION: A higher RA activity rate was observed. This may be related to difficultly accessing rheumatology clinics in our facility and financial difficulties accessing biological treatments.

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database.

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CONCLUSIONS: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc.

Depression, sleep disturbances, pain, disability and quality of LIFE in Brazilian Fabry disease patients.

BACKGROUND: Fabry disease (FD) is a lysosomal disease in which mutations affect the GLA gene located on the X chromosome. The defective product, the enzyme alpha-galactosidase A, causes accumulation of substrate and contributes to the disruption of cell function in several organs, with variable severity and consequent damage of tissue or organ function. Patient reported outcomes (PROs) enable patients to provide information regarding the consequences of their disease and its treatment and are often recognized as the most important outcomes for them. OBJECTIVES: To evaluate pain, depression, sleep disturbances, disability and disease impact on quality of life in a cohort of Brazilian FD patients and compare between groups stratified by the Mainz Symptom Severity Index (MSSI) Methods: Thirty-seven genotype confirmed classic FD patients - 16 male and 21 female - (mutations: C142R, A156D, L180F, R227X, W262X, G271A, P293S, Y264SX) were evaluated and answered the following questionnaires: Brief Pain Inventory (BPI), Hamilton Depression Rating Scale (HAM-D), Pittsburgh Sleep Quality Index (PSQI), Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form Health Survey 36 (SF-36). RESULTS: In FD patients, mean ± SD BPI severity result was 2.78 ± 2.66 for severe; 2.80 ± 2.55 for moderate and 1.55 ± 2.38 for mild severity patients. Mean ± SD BPI interference result was 2.55 ± 2.44 for severe; 2.80 ± 3.18 for moderate and 1.36 ± 2.83 for mild patients. BPI severity and interference values correlated with MSSI scores (r = 0.24; p < .001 / r = 0.25; p < .001). Application of HAM-D indicated depression in 21 patients (56.8%). HAM-D results had positive correlation with MSSI values (r = 0.21; p < .001), with BPI severity (r = 0.54; p < .001) and interference (r = 0.65; p < .001). PSQI depicted sleep disturbances in 22 patients (59.5%). PSQI values correlated with MSSI values (r = 0.25; p < .001), with HAM-D results (r = 0.65; p < .001) and BPI severity (r = 0.47; p < .001) and interference (r = 0.66; p < .001). Mean HAQ-DI result was 0.490 for severe; 0.274 for moderate and 0.157 for mild severity patients. CONCLUSIONS: Depression, sleep disturbances and disability were under-recognized in FD patients. HAQ-DI revealed worse disability according to MSSI severity status. The lowest raw scores from the SF-36 questionnaire were for the domains general health perception and physical role functioning. Standardized assessments should be routine care and started as early as diagnosis of Fabry disease is made.