Adjunct role of potassium-rich vegetarian diet and a novel potassium food supplement to improve pain in chronic rheumatoid arthritis on supervised standard care: a randomised controlled study.

Introduction: An earlier food survey showed dietary potassium deficiency in rheumatoid arthritis (RA). Objective: To evaluate an adjunct role of oral potassium to reduce joint pain in RA. Methods: 172 consenting eligible symptomatic patients (median duration 6.5 years) on standard care were randomised into an assessor blind, parallel efficacy, controlled, prospective, multiarm single-centre study (80% power, drug trial design) of 16 weeks duration-arm A (potassium-rich vegetarian diet), arm B (arm A plus novel potassium food supplement) and arm C (control, regular diet). Standard efficacy (American College of Rheumatology recommendation) and safety and diet intake (3-day recall) were assessed at monthly intervals (protocol). Standard soft-ware package (SPSS V.20) was used for statistical analysis; analysis of variance), Mann-Whitney statistic and χ2 test.; significant p<0.05, two sided). Study arms were found matched at baseline. Background RA medication remained stable. Preset target for increased potassium intake (India standards) were mostly achieved and participants remained normokalemic. Results: 155 patients (90.1%) completed the study and several showed improvement (maximum improved measures in arm B). Potassium intervention was safe and well tolerated. Adverse events were mild; none caused patient withdrawal. On comparison, the mean change in pain visual analogue scale (-2.23, 95% CI -2.99 to -1.48) at week 16 (primary efficacy) from baseline was significantly superior in arm B (per protocol analysis). A high daily potassium intake (5-7.5 g, arm B) was significantly associated with low pain (study completion); OR 2.5 (univariate analysis), likelihood ratio 2.9 (logistic regression). Compliance (intervention), diet record and analysis, RA medication and absence of placebo were potential confounders. Conclusion: High oral potassium intake, based on a suitable vegetarian diet and food supplement, reduced joint pain and improved RA. It was a safe adjunct to standard care, Further validation studies are required. Trial registration: CTRI/2022/03/040726; Clinical Trial Registry of India.

Country-level socioeconomic status relates geographical latitude to the onset of RA: a worldwide cross-sectional analysis in the METEOR registry.

OBJECTIVE: Age at rheumatoid arthritis (RA) onset varies by geographical latitude. We have investigated to what extent differences in patient-specific factors and country-level socioeconomic indicators explain this variability. METHODS: Patients with RA from the worldwide METEOR registry were included. Bayesian multilevel structural equation models were used to study the relationship between the absolute value of (hospital) geographical latitude and age at diagnosis (as a proxy for age at RA onset). We examined to what extent this effect is mediated by individual patient characteristics and by country-specific socioeconomic indicators and disentangled whether the observed effects occurred at the patient, hospital, or country levels. RESULTS: We included 37 981 patients from 93 hospitals in 17 geographically widespread countries. Mean age at diagnosis per country ranged from 39 (Iran) to 55 (Netherlands) years. Per degree increase in country latitude (between 9.9° and 55.8°), mean age at diagnosis increased by 0.23 years (95% credibility interval: 0.095 to 0.38) (reflecting >10 years difference in age at RA onset). For hospitals within a country, this latitude effect was negligible. Inclusion of patient-specific factors (eg, gender, anticitrullinated protein antibodies status) in the model augmented the main effect from 0.23 to 0.36 years. Inclusion of country-level socioeconomic indicators (eg, gross domestic product per capita) in the model almost effaced the main effect (from 0.23 to 0.051 (-0.37 to 0.38)). CONCLUSIONS: Patients living closer to the equator get RA at a younger age. This latitude gradient was not explained by individual patient characteristics, but rather by countries' socioeconomic status, providing a direct link between countries' level of welfare and the clinical onset of RA.

Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

The Long-Term Effects of Short-Period Adalimumab Biosimilar Usage in Ankylosing Spondylitis.

Background Cost and drug toxicity frequently deter the long-term use of anti-tumor necrosis factor (TNF) agents in ankylosing spondylitis (AS). Therefore, this study was conducted to observe long-term relief after the short-term administration of an anti-TNF agent. Methodology A one-year, prospective, interventional, uncontrolled, single-center trial was conducted. There were 50 patients with symptomatic active chronic AS who received rheumatology therapy and were anti-TNF naive. Every two weeks, 40 mg of standard biosimilar adalimumab (Bs-ADA, Exemptia™) was administered subcutaneously for six injections (10 weeks) or to continue with standard follow-up if they did not achieve an Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) index response by week 12. Standard indicators (Assessment Spondyloarthritis International Society/ASAS and Bath) were used to evaluate progress. In addition, TNF-alpha, interleukin (IL)-6, and IL-17 were tested using a commercially available enzyme-linked immunosorbent assay kit from Bio Legend (Bengaluru, India). Results Patients experienced early and significant improvement in pain, non-steroidal anti-inflammatory drugs (NSAIDs) requirement, function, and several indices (ASAS 20 and 40, ASAS partial remission, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score) after discontinuing injections. At weeks 12 and 48, 84% and 52% of patients showed ASAS 20 improvement, with 34% and 24% showing ASAS partial remission. Over half of the patients continued to improve and provided proof of concept. Conclusions In difficult-to-treat AS, a 10-week course of biosimilar adalimumab demonstrated significant early improvement that often lasted for 24 weeks. This unconventional method proved to be economically appealing. It merits further confirmation and acceptance, especially in resource-constrained contexts.

Corrigendum: Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

[This corrects the article DOI: 10.3389/fmed.2022.761655.].

Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

INTRODUCTION: Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. METHODS AND ANALYSIS: We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].

Withania somnifera as a safer option to hydroxychloroquine in the chemoprophylaxis of COVID-19: Results of interim analysis.

OBJECTIVES: To study the efficacy and safety of Withania somnifera (WS, Ashwagandha) in the prophylaxis against COVID-19 in high risk health care workers (HCW) in comparison to hydroxychloroquine (HCQ). To evaluate the general physical and mental health benefits of Ashwagandha. METHODS: A 16 week randomized prospective, open-label, parallel efficacy, two arm, multi-centre study. The primary efficacy measure was 'failure of prophylaxis' as confirmed COVID-19 by quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) at any time during the study period. This study on 400 participants from three centres was designed to establish non-inferiority for WS to HCQ for prophylaxis against COVID-19 at 80 % power and significance p < 0.025, one-sided. The interim analysis was carried out on 160 participants after completion of 8 weeks. RESULTS: Participants in both the arms were well-matched at the baseline characteristics. Forty participants in the HCQ group and 26 participants in the WS group reported mild AE. The symptoms of confirmed COVID-19 were found to be 3.7 % (95 % CI 1.3-10.5 %) in the HCQ and 1.3 % (95 % CI 0.02-6.7 %) in the WS arm amongst the first 160 participants completing 8 weeks. CONCLUSION: Our intent was to explore a safer option to HCQ. We report that WS was not found inferior to HCQ and its efficacy was within the 15 % non-inferiority margin set a priori. WS as an immunomodulator has other clinical benefits including reducing mental stress. The final report of this study is expected by end of August 2021.

Rheumatoid arthritis management in the APLAR region: Perspectives from an expert panel of rheumatologists, patients and community oriented program for control of rheumatic diseases.

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.

Phenotype and treatment of elderly onset compared with younger onset rheumatoid arthritis patients in international daily practice.

OBJECTIVE: To identify possible differences in baseline characteristics, initial treatment and treatment response between RA patient subgroups based on age at disease onset. METHODS: Daily practice data from the worldwide METEOR registry were used. Patients (7912) were stratified into three age-groups (age at disease diagnosis <45 years, 45-65 years, >65 years). Initial treatment was compared between the different age-groups. With Cox regression analyses the effect of age-group on time-to-switch from first to second treatment was investigated, and with linear mixed models differences in response to treatment (DAS and HAQ) between the age-groups were assessed, after correction for potential confounders. RESULTS: The >65 years age-group included more men, and more seronegative RA with somewhat higher inflammatory markers. Initial treatment choices differed only slightly between the age-groups, and the time-to-switch from initial treatment to the next was similar. DAS and HAQ improvement were dependent on the age-group, reflected by a significant interaction between age-group and outcome. The stratified analysis showed a difference of -0.02 and -0.05 DAS points and, -0.01 and 0.02 HAQ points per month in the <45 and 45-65 years age-groups as compared with the >65 year age group, a difference that did not seem clinically relevant. CONCLUSION: In this international study on worldwide clinical practice, patients with RA onset >65 years include more men and seronegative arthritis, and were initially treated slightly differently than younger patients. We observed no clinically relevant differences in timing of a next treatment step, or response to treatment measured by DAS and HAQ.

Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial.

OBJECTIVES: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. METHODS: This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24. RESULTS: The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments. CONCLUSIONS: FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

PURPOSE OF THE REVIEW: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. RECENT FINDINGS: Sixteen RCTs of up to 16 weeks duration including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain (SMD - 0.82, 95% CI - 1.17 to - 0.47, I2 = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc analysis of efficacy and safety in Phase 3 and long-term extension studies over 7 years.

OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients. METHODS: Efficacy data were pooled for disease-modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate-naïve) and ORAL Sequel (long-term extension [LTE] study; data cut-off March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire-Disability Index. Incidence rates (IRs; patients with events/100 patient-years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison. RESULTS: One-hundred-and-ninety-seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non-smokers and all were biologic DMARD (bDMARD)-naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25). CONCLUSIONS: Tofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD-treated RA patients from high-risk countries (IR = 0.00-2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.

Association of 17 Definitions of Remission with Functional Status in a Large Clinical Practice Cohort of Patients with Rheumatoid Arthritis.

OBJECTIVE: To compare the association between different remission criteria and physical function in patients with rheumatoid arthritis followed in clinical practice. METHODS: Longitudinal data from the METEOR database were used. Seventeen definitions of remission were tested: American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean-based; Simplified/Clinical Disease Activity Index (SDAI/CDAI); and 14 Disease Activity Score (DAS)-based definitions. Health Assessment Questionnaire (HAQ) ≤ 0.5 was defined as good functional status. Associations were investigated using generalized estimating equations. Potential confounders were tested and sensitivity analyses performed. RESULTS: Data from 32,915 patients (157,899 visits) were available. The most stringent definition of remission was the ACR/EULAR Boolean-based definition (1.9%). The proportion of patients with HAQ ≤ 0.5 was higher for the most stringent definitions, although it never reached 100%. However, this also meant that, for the most stringent criteria, many patients in nonremission had HAQ ≤ 0.5. All remission definitions were associated with better function, with the strongest degree of association observed for the SDAI (adjusted OR 3.36, 95% CI 3.01-3.74). CONCLUSION: The 17 definitions of remission confirmed their validity against physical function in a large international clinical practice setting. Achievement of remission according to any of the indices may be more important than the use of a specific index. A multidimensional approach, targeted at wider goals than disease control, is necessary to help all patients achieve the best possible functional status.

Household air pollution and arthritis in low-and middle-income countries: Cross-sectional evidence from the World Health Organization's study on Global Ageing and Adult Health.

BACKGROUND: Evidence points to a clear link between air pollution exposure and several chronic diseases though investigations regarding arthritis are still lacking. Emerging evidence suggests an association between ambient air pollution and rheumatoid arthritis. Household air pollution exposure, conversely, is largely unstudied but may be an important consideration for arthritis, particularly in low- and middle-income countries (LMICs), where cooking and heating activities can generate high indoor air pollutant levels. METHODS: We investigated the association of household air pollution (electricity vs. gas; kerosene/paraffin; coal/charcoal; wood; or agriculture/crop/animal dung/shrubs/grass as the main fuel used for cooking) and arthritis in six LMICs (China, Ghana, India, Mexico, the Russian Federation, South Africa) using data from Wave I of the World Health Organization Study on Global AGEing and Adult Health (SAGE) (2007-2010). Multivariable analyses were adjusted for sociodemographic, household and lifestyle characteristics and several comorbidities. RESULTS: The use of gas (aOR = 1.76, 95%CI: 1.40-2.21); coal (aOR = 1.74, 95%CI: 1.22-2.47); wood (aOR = 1.69, 95%CI: 1.30-2.19); or agriculture/crop/animal dung/shrubs/grass: aOR = 1.95 (1.46-2.61) fuels for cooking were strongly associated with an increased odds of arthritis, compared to electricity in cluster and stratified adjusted analyses. Gender (female), age (≥50 years), overweight (25.0 ≤BMI<30.0 kg/m2), obesity (BMI ≥30.0 kg/m2), former and current alcohol consumption, and the comorbidities angina pectoris, diabetes, chronic lung disease, depression and hypertension were also associated with a higher odds of arthritis. Underweight (BMI<18.5 kg/m2) and higher education levels (college/university completed/post-graduate studies) were associated with a lower odds of arthritis. CONCLUSIONS: These findings suggest that exposure to household air pollution from cook fuels is associated with an increased odds of arthritis in these regions, which warrants further investigation.

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

Objective: To investigate associations between baseline presence of erosions and/or anti-citrullinated protein antibodies (ACPA) on functional ability, disease activity and treatment survival over time. Methods: Real life data from newly diagnosed rheumatoid arthritis patients were identified in the international METEOR registry. Patients were grouped according to presence/absence of ACPA and/or erosions at baseline. Associations between the presence of ACPA and/or erosions (four groups) with the change of Disease Activity Score (DAS) and Health Assessment Questionnaire (HAQ) over time were assessed using linear mixed models during maximum 6 or maximum 12 months from baseline. Treatment survival was assessed using multiple failure-times Cox regression. Results: Data were included from 701 ACPA‒/erosions‒, 334 ACPA‒/erosions+, 1585 ACPA+/erosions‒ and 1993 ACPA+/erosions+ patients. We found statistically significant differences in DAS and HAQ change over time between the four groups, both after maximum follow-up durations of 6 and of 12 months, but after stratification differences proved small and not clinically meaningful. Patients in the ACPA‒/erosions‒ group were less likely to switch treatment compared with the ACPA+/erosions‒ reference group (p<0.001). The other two ACPA/erosions groups did not differ from the reference group. Conclusions: In this analysis of worldwide real life data, we found statistically significant, but clinically irrelevant differences in treatment response to initial disease modifying anti-rheumatic drug therapies as measured by DAS and HAQ in ACPA‒/erosions‒, ACPA‒/erosions+, ACPA+/erosions‒ and ACPA+/erosions+ rheumatoid arthritis patients. However, after maximum follow-up durations of 6 and 12 months all groups had a similar response to initial treatment, but with a lower likelihood to switch treatment for ACPA‒/erosions‒ patients during the first year of follow-up.

Impact of Patient's Global Assessment on Achieving Remission in Patients With Rheumatoid Arthritis: A Multinational Study Using the METEOR Database.

OBJECTIVE: There is an ongoing debate about excluding patient's global assessment (PtGA) from composite and Boolean-based definitions of rheumatoid arthritis (RA) remission. This study aimed at determining the influence of PtGA on RA disease states, exploring differences across countries, and understanding the association between PtGA, measures of disease impact (symptoms), and markers of disease activity (inflammation). METHODS: Cross-sectional data from the Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology international database were used. We calculated the proportion of patients failing American College of Rheumatology/European League Against Rheumatism Boolean-based remission (4-variable remission) solely due to PtGA (PtGA-near-remission) in the overall sample and in the most representative countries (i.e., those with >3,000 patients in the database). Multivariable linear regression models were used to identify the main determinants of PtGA, grouped in predominantly inflammatory impact factors (28 tender joint counts, 28 swollen joint counts, and C-reactive protein level) and disease impact factors (pain and function). RESULTS: This study included 27,768 patients. Excluding PtGA from the Boolean-based definition (3-variable remission) increased the remission rate from 5.8% to 15.8%. The rate of PtGA-near-remission varied considerably between countries, from 1.7% in India to 17.9% in Portugal. One-third of the patients in PtGA-near-remission group scored PtGA >4 of 10. Pain and function were the main correlates of PtGA, with inflammation-related variables contributing less to the model (R2 = 0.57). CONCLUSION: PtGA is moderately related to joint inflammation overall, but only weakly so in low levels of disease activity. A considerable proportion of patients otherwise in biologic remission still perceive high PtGA, putting them at risk of excessive immunosuppressive treatment.

Autoantibody status is not associated with early treatment response to first-line methotrexate in patients with early rheumatoid arthritis.

Objectives: In RA, the relationship between autoantibody status and treatment response to MTX remains unclear. We investigated the association between autoantibody status and early remission in newly diagnosed RA patients treated with MTX using real-world data. Methods: RA-patients initially treated with MTX were selected from an international observational database (METEOR). Patients were stratified into autoantibody-positive (RF- and/or ACPA-positive) or autoantibody negative (RF- and ACPA-negative). The effect of autoantibody status on the chance of achieving remission within 3 to 6 months was analysed using Cox-proportional hazards regression. Results: Data from 1826 RA patients were available for analysis. DAS remission was achieved in 17% (318/1826). This was similar in autoantibody-positive [17% (282/1629)] and -negative patients [18% (36/197)]. Hence, autoantibody positivity was not associated with remission [hazard ratio (HR) 0.89, 95% CI 0.57, 1.38]. Similar findings were found when stratified for MTX monotherapy (HR 0.75, 95% CI 0.41, 1.37) or combination treatment (HR 0.76, 95% CI 0.37, 1.54). Good physical function (HAQ < 0.5) was achieved in 33% (530/1590) of all patients. Autoantibody-positivity was also not associated with HAQ < 0.5 (HR 1.05, 95% CI 0.71, 1.57). Conclusion: Autoantibody status is not associated with early remission in newly diagnosed RA-patients receiving MTX. This indicates that MTX is effective as an initial treatment strategy regardless of autoantibody status.

How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a multiple propensity score to adjust for confounding by indication in observational studies.

OBJECTIVES: To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication. METHODS: Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS. RESULTS: After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95% CI) of -2.00 (-2.65 to -1.36) if patients received a bDMARD; of -0.96 (-1.33 to -0.59) if patients received csDMARD(s)+glucocorticoids and of -0.73 (-1.21 to -0.25) if patients received csDMARDs only. These changes were -0.91 (-1.23 to -0.60); -0.43 (-0.62 to -0.23) and -0.39 (-0.66 to -0.13), respectively after 1 year of follow-up. CONCLUSIONS: In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.

Clinical Profile of Primary Sjogren's Syndrome with Hypokalemic Periodic Paralysis.

Introduction: Primary Sjogren's Syndrome (pSS) with Hypokalemic Periodic Paralysis(HPP) whether an association or a different clinical subset needs review. Methods: Cross-sectional retrospective study of subjects of Primary Sjogren's Syndrome with Hypokalemic Periodic Paralysis(HPP) identified from database maintained at Centre For Rheumatic Diseases, Pune since 1996 with records of over 50000 patients. The diagnosis was clinical. Clinical and investigations data was extracted pertaining to initial examination and follow up. Standard investigations & ELISA, immunoblot and nephelometry to assay autoantibodies (AAb) were done. Results: 16 patients of Primary Sjogren's Syndrome (pSS) with Hypokalemic Periodic Paralysis (HPP) were identified in the period 2000-2014. Presenting feature was HPP in 86% with Dry eye (4%) and Arthralgias (10%) in remaining. Distal Renal Tubular Acidosis was identified in all. All were females with average age of 26 years. Symptomatic ocular sicca noted in 60% & Oral sicca in 50% patients. Other features - Arthralgias (91%), arthritis (42%), mucositis (38%), Neuropathy (30%), skin rash (20%) cytopenias (19%), Erosive arthritis (10%), interstitial lung disease (10%) and Raynaud Phenomenon (10%). 100% were positive for ANA. SSA was positive in 100%, SSB in 50% of patients & Rheumatoid Factor in 70 %. Hypothyroidism was associated in 70% patients. Conclusion: We present a large series of Primary Sjogren's Syndrome with Hypokalemic Periodic Paralysis(HPP) from India. Prominent features of female dominance, younger age of onset and SSA positivity noted in this cohort of patients on Routine clinical and serology phenotype suggests existence of a distinct subset. HPP was presenting feature in majority.