Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data.

In this commentary, we review clinical data which helps inform individualized benefit-risk assessment for tofacitinib in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). ORAL Surveillance, a safety trial of patients ≥ 50 years of age with rheumatoid arthritis (RA) and cardiovascular risk factors, found increased rates of safety outcomes (including major adverse cardiovascular events [MACE], malignancies excluding non-melanoma skin cancer, and venous thromboembolism) with tofacitinib versus tumor necrosis factor inhibitors (TNFi). Post hoc analyses of ORAL Surveillance have identified subpopulations with different relative risk versus TNFi; higher risk with tofacitinib was confined to patients ≥ 65 years of age and/or long-time current/past smokers, and specifically for MACE, patients with a history of atherosclerotic cardiovascular disease (ASCVD). In patients without these risk factors, risk differences between tofacitinib and TNFi could not be detected. Given differences in demographics, pathophysiology, and comorbidities, we sought to examine whether the risk stratification observed in RA is also appropriate for PsA and AS. Data from the PsA tofacitinib development program show low absolute risk of safety outcomes in patients < 65 years of age and never smokers, and low MACE risk in patients with no history of ASCVD, consistent with results from ORAL Surveillance. No MACE, malignancies, or venous thromboembolism were reported in the tofacitinib AS development program. The mechanism of the ORAL Surveillance safety findings is unknown, and there are no similar prospective studies of sufficient size and duration. Accordingly, it is appropriate to use a precautionary approach and extrapolate differentiating risk factors identified from ORAL Surveillance (age ≥ 65 years, long-time current/past smoking, and history of ASCVD) to PsA and AS. We recommend an individualized approach to treatment decisions based on these readily identifiable risk factors, in line with updated labeling for Janus kinase inhibitors and international guidelines for the treatment of PsA and AS.Trial Registration: NCT02092467, NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02281552, NCT02187055, NCT02831855, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364, NCT00678210, NCT01710046, NCT01241591, NCT01186744, NCT01276639, NCT01309737, NCT01163253, NCT01786668, NCT03502616.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets.

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.

Establishing language and ethnic equivalence for health-related quality of life item banks and testing their efficiency via computerised adaptive testing simulations.

PURPOSE: We aimed to (1) establish linguistic and ethnic equivalence (i.e. lack of bias) for the items in the English and Chinese versions of the Singapore Health and Well Being (SHAWS) Physical Functioning (PF), Positive Mindset (PM) and Social Relationship (SR) item banks (IBs); and (2) evaluate the preliminary efficiency of these IBs using Computer Adaptive Testing (CAT) simulations. METHODS: In this cross-sectional study, 671, 670, and 672 subjects answered 55, 48 and 30 items of the PF, PM, and SR IBs, respectively. Rasch analysis was conducted to assess each IB's psychometric properties, particularly the presence of differential item functioning (DIF) for language and ethnicity. A set of performance criteria related to removing items that displayed notable DIF were employed. CAT simulations determined the mean number of items for high, moderate, and moderate-low measurement precisions (stopping rule: SEM 0.300, 0.387. 0.521, respectively). RESULTS: Half of subjects were >50 years old (40.9% PF, 42.1% PM, 41.4% SR), Chinese (50.7% PF, 51.0% PM, 50.6% SR) and female (50.0% PF. 49.4% PM, 52.8% SR) respectively. Rasch analysis revealed 4 items with DIF for the PF IB, 9 items with DIF for the PM IB and 2 items with DIF for the SR IB. In CAT simulations, the mean number of items administered was 8.5, 21.6 and 14.5 for the PF, PM and SR IBs, respectively (SEM 0.300), 5.1, 13.0, 8.0 for PF, PM and SR IBs, respectively (SEM 0.387) and 3.1, 5.3 and 4.1 for PF, PM and SR IBs, respectively (SEM 0.521). CONCLUSION: The PF, PM and SR IBs to measure health-related quality of life revealed minimal DIF for language and ethnicity after remedial efforts. CAT simulations demonstrated that these IBs were efficient, especially when the stopping rule was set at moderate precision, and support the implementation of the SHAWS IBs into routine clinical care.

Association of adipokines with severity of knee osteoarthritis assessed clinically and on magnetic resonance imaging.

Objectives: We aimed to evaluate the association between the adipokines: Leptin, Adiponectin, Resistin, and high sensitive-C-reactive protein (hs-CRP) with clinical, radiographical and magnetic resonance imaging (MRI) assessment of knee osteoarthritis (OA) severity. Design: We performed a cross-sectional study in participants with earlier knee OA. Demographics, clinical (WOMAC), radiographical and MRI (BLOKS scoring) severity of knee OA were assessed. Serum leptin, adiponectin, resistin and hs-CRP were measured. Association of adipokines and hs-CRP with clinical, radiographic and MRI severity outcomes were evaluated using regression models with adjustment with age, sex, and body mass index (BMI). Results: 137 participants with earlier knee OA (82% women, mean â€‹± â€‹SD age: 55.5 â€‹± â€‹7.8 years) were included. Participants had moderate knee OA symptoms, mean WOMAC pain and function were 30.6 â€‹± â€‹18.0, and 31.7 â€‹± â€‹19.8 respectively. Mean BMI was 27.0 â€‹± â€‹5.9 â€‹kg/m2. After adjustment with age, sex and BMI, serum leptin was positively associated with osteophyte size, cartilage integrity, infrapatellar synovitis and effusion. While hs-CRP was associated with meniscus extrusion and adiponectin was associated with WOMAC pain and function. Conclusion: Serum adipokines, particularly leptin was associated with severity of various structural defects of the knee joint on MRI beyond age, sex and BMI in earlier knee OA.

Social cognitive theory to improve symptom appraisal and help-seeking among patients with autoimmune rheumatic diseases: A qualitative study.

AIM: Social cognitive theory (SCT) has been successfully employed to improve symptom appraisal and help-seeking among patients with various conditions but is yet to be applied in the context of autoimmune rheumatic diseases (ARDs). This study aimed to explore the applicability of SCT in and possible approaches to improving symptom appraisal and help-seeking of patients with ARDs, one of the key barriers to earlier diagnosis. METHODS: Semi-structured interviews were conducted with 33 ARD patients with a prolonged pre-diagnosis interval (>3 months). We coded the transcripts deductively using SCT as the overarching framework and inductively for approaches identified from the interviews. RESULTS: All six main concepts of SCT (behavioral capacity, expectations, self-efficacy, observational learning, reinforcements, and reciprocal determinism) were observed in the three stages of symptom appraisal and help-seeking (detection, interpretation, and response) of patients with ARDs. While many participants reported that they were able and confident to detect their symptoms, they lacked the behavioral capacity and self-efficacy to interpret symptoms correctly, which resulted in delayed help-seeking and diagnosis. Possible approaches to address this suggested by participants (such as education of the general population) could improve behavioral capacity and self-efficacy in symptom interpretation and enhance expectations, observational learning, reinforcements, and reciprocal determinism in symptom response. CONCLUSION: Lack of behavioral capacity and self-efficacy was observed in symptom interpretation of patients with ARDs, which resulted in delayed help-seeking. Approaches could target the behavioral capacity and self-efficacy for symptom interpretation to facilitate early help-seeking and, in turn, earlier diagnosis among individuals with possible ARDs.

Association between obesity and likelihood of remission or low disease activity status in psoriatic arthritis applying index-based and patient-based definitions of remission: a cross-sectional study.

OBJECTIVES: We aimed to evaluate whether obese patients with psoriatic arthritis (PsA) were less likely to be in remission/low disease activity (LDA). METHODS: We used data from the ReFlaP, an international multi-centre cohort study (NCT03119805), which recruited consecutive adults with definite PsA (disease duration ≥ 2 years) from 14 countries. Demographics, clinical data, comorbidities, and patient-reported outcomes were collected. Remission/LDA was defined as Very Low Disease Activity (VLDA)/minimal disease activity (MDA), Disease Activity in PSoriatic Arthritis (DAPSA) ≤4/≤14, or by patients' opinion. Obesity was defined as physician-reported and/or body mass index ≥30 kg/m2. We evaluated the association between obesity and the presence of remission/LDA, with adjustment in multivariable regression models. RESULTS: Among 431 patients (49.3% women), 136 (31.6%) were obese. Obese versus non-obese patients were older, more frequently women, had higher tender joint and enthesitis counts and worse pain, physical function and health-related quality of life. Obese patients were less likely to be in VLDA; DAPSA remission and MDA, with adjusted ORs of 0.31 (95% CI 0.13 to 0.77); 0.39 (95% CI 0.19 to 0.80) and 0.61 (95% CI 0.38 to 0.99), respectively. Rates of DAPSA-LDA and patient-reported remission/LDA were similar for obese and non-obese patients. CONCLUSION: PsA patients with comorbid obesity were 2.5-3 folds less likely to be in remission/LDA by composite scores compared with non-obese patients; however, remission/LDA rates were similar based on the patients' opinion. PsA patients with comorbid obesity may have different disease profiles and require individualised management.

Recommendations for enhanced primary series (third dose) COVID-19 vaccination for people with rheumatic diseases: Chapter of Rheumatologists, College of Physicians, Singapore.

Introduction: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. Methods: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. Results: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. Conclusion: These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study.

OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Symptom Appraisal and Help-Seeking Among Patients With Autoimmune Rheumatic Diseases: A Qualitative Study.

OBJECTIVE: Long diagnostic delay remains an unsolved problem in many autoimmune rheumatic diseases (ARDs). One of the major contributing factors is poor symptom appraisal and the resulting delays in help-seeking by patients themselves. We therefore aimed to understand the symptom appraisal and help-seeking experience among patients with ARDs in a multiethnic urban Asian population and to explore its influencing factors. METHODS: Semistructured interviews with 33 patients with ARDs were audio recorded and transcribed verbatim. We coded the transcripts deductively using the reported 3 stages of symptom appraisal (detection, interpretation, and response) as the framework, and inductively for newly emerging themes and subthemes. RESULTS: All 3 stages of the symptom appraisal and help-seeking journey (ie, symptom detection [by self and by others], symptom interpretation [causes, consequences, and required actions] and symptom response [no action, self-management, seeking help from nonhealthcare professionals, and seeking help from healthcare professionals]) were observed among patients. Interactions among these 3 stages were also observed: symptom interpretation was found to influence subsequent symptom detection, and the outcome of symptom response was found to influence both subsequent symptom detection and symptom interpretation. Various personal and socioenvironmental factors (eg, knowledge and cultural beliefs about the symptom) that influenced symptom appraisal and help-seeking were identified from the interviews. CONCLUSION: The symptom appraisal and help-seeking journey of patients with ARDs is an iterative process of detection, interpretation, and response, and is influenced by various personal and socioenvironmental factors. Addressing modifiable factors could shorten the symptom appraisal and help-seeking interval and improve patient outcomes.

Initiating Evaluation of Composite Outcome Measures for Psoriatic Arthritis: 2022 Updates From the GRAPPA-OMERACT Working Group.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) working group-comprising rheumatologists, dermatologists, methodologists, and patient research partners-provided updates at the GRAPPA 2022 annual meeting on its work to evaluate composite outcome measures for PsA. Ten composite outcome measures were considered. Initial steps were to define the population, the purpose of use, and the proposed pros and cons of the 10 candidate composite instruments for PsA. Preliminary Delphi exercises within the working group and GRAPPA stakeholders confirmed high priority for evaluating minimal disease activity (MDA); moderate priority for Disease Activity in PsA (DAPSA), American College of Rheumatology (ACR) response criteria, Psoriatic Arthritis Disease Activity Score (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), 3 visual analog scale (VAS), and 4VAS; and low priority for Disease Activity Score in 28 joints (DAS28), Psoriatic Arthritis Responder Criteria (PsARC), and Routine Assessment of Patient Index Data 3 (RAPID3). Further appraisal of candidate composite instruments is ongoing.

Improvements in work productivity among patients with inflammatory arthritis and osteoarthritis in the first six months after diagnosis: an inception cohort study.

OBJECTIVES: Reduced work productivity (WP), measured by work productivity loss (WPL) and work disability (WD), is common in patients with inflammatory arthritis (IA) and osteoarthritis (OA) but is not well characterised. We aimed to assess if there were any improvements in WP (WPL and WD) from diagnosis (T1) to six months later (T2) and to explore associations between WP at T2 and health status at T1 among these patients. METHODS: Patients were surveyed for work characteristics, work ability, WP and health status including physical functioning and vitality at T1 and T2. Associations between WP at T2 and health status at T1 were explored using regression models. RESULTS: Patients with IA (n=109) were younger than those with OA (n=70) (mean age: 50.5 vs. 57.7 years). The median WPL score decreased from 30.0 to 10.0 in patients with IA and from 20.0 to 0.0 in patients with OA, while the proportion reporting WD decreased from 52.3% to 45.3% in patients with IA and increased from 52.2% to 56.5% in patients with OA from T1 to T2. Physical functioning at T1 (coefficient = -0.35) was significantly associated with WPL at T2. Vitality at T1 (coefficient = 0.03) was associated with WD at T2. CONCLUSIONS: Greater improvements in WP were observed among patients with IA than those with OA in the first six months after diagnosis. This provides a basis for healthcare professionals to aim for greater improvements in work and health status for patients with IA.

Association between baseline cardiovascular risk and incidence rates of major adverse cardiovascular events and malignancies in patients with psoriatic arthritis and psoriasis receiving tofacitinib.

Background: Tofacitinib is a Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA) and has been investigated for psoriasis (PsO). Objectives: This post hoc analysis examined baseline cardiovascular (CV) disease risk and its association with the occurrence of major adverse cardiovascular events (MACE) and malignancies in tofacitinib-treated patients with PsA and PsO. Design: Included three phase III/long-term extension (LTE) PsA trials and seven phase II/phase III/LTE PsO trials of patients receiving ⩾ 1 dose of tofacitinib. Methods: Incidence rates (IRs: patients with events/100 patient-years) for MACE and malignancies (excluding non-melanoma skin cancer) were determined in subgroups according to history of atherosclerotic CV disease (ASCVD), baseline 10-year risk of ASCVD (in patients without history of ASCVD), and baseline metabolic syndrome (MetS). Results: For patients with PsA (N = 783) and PsO (N = 3663), respectively, tofacitinib exposure was 2038 and 8950 patient-years (median duration: 3.0 and 2.4 years), and 40.9% and 32.7% had MetS. Excluding missing CV risk profile data, 51/773 (6.6%) and 144/3629 (4.0%) patients had history of ASCVD, and in patients without history of ASCVD, around 20.0% had intermediate/high baseline 10-year ASCVD risk. For PsA and PsO, IRs of MACE were greatest in those with history of ASCVD or high baseline 10-year ASCVD risk. For PsA, five of six patients with MACE had baseline MetS. Malignancy IRs in patients with PsA were greatest in those with intermediate/high baseline 10-year ASCVD risk. Of these, eight of nine patients with malignancies had baseline MetS. In the PsO cohort, IR of malignancies was notably greater with high versus low/borderline/intermediate baseline 10-year ASCVD risk. Conclusion: In tofacitinib-treated patients with PsA/PsO, increased ASCVD risk and baseline MetS were associated with higher IRs for MACE and malignancies. Our results support assessing CV risk in patients with PsA/PsO and suggest enhanced cancer monitoring in those with increased ASCVD risk. Registration ClinicalTrialsgov: NCT01877668/NCT01882439/NCT01976364/NCT00678210/NCT01710046/NCT01241591/NCT01186744/NCT01276639/NCT01309737/NCT01163253. Plain Language Summary: People who have psoriatic arthritis or psoriasis may have more heart-related problems and cancer if they have a higher risk of cardiovascular disease: A study in people with psoriatic arthritis or psoriasis receiving tofacitinib Why was this study done? • People with psoriatic arthritis (PsA) and psoriasis (PsO) are more likely than the general population to have a disease affecting the heart and blood vessels [cardiovascular (CV) disease].• People who are more likely to have CV disease may also be more likely to have certain types of cancer.• Tofacitinib is a medicine to treat people with PsA and has been tested in people with PsO.• We wanted to know if the risk of CV disease affects the number of heart-related problems (including heart attack, stroke, or death) and cancer in people with PsA and PsO. What did the researchers do? • We used results from 10 clinical trials.• In these trials, people with PsA and PsO were taking tofacitinib 5 or 10 mg twice a day.• After the trials had ended, we measured people's risk of CV disease using a risk calculator. This risk calculator showed if they had a low, borderline, intermediate, or high risk of CV disease over the next 10 years. We also checked if they had had CV disease before treatment.• We checked if people had a group of conditions linked to CV disease: diabetes, high blood pressure, and obesity.• We counted the cases of heart-related problems and cancer in people once they started taking tofacitinib. What did the researchers find? In people with PsA and PsO taking tofacitinib:• There were more cases of heart-related problems and cancer in people who had intermediate or high risk of CV disease.• There were more cases of heart-related problems in people who had had CV disease before.• More people with diabetes, high blood pressure, and obesity had heart-related problems and cancer than people without those conditions. What do the findings mean? • It is important to measure risk and assess history of CV disease in people with PsA and PsO, including those taking tofacitinib.• We should test for cancer in people with high risk of CV disease.

Gut microbiome profiling in systemic sclerosis: a metagenomic approach.

OBJECTIVES: The early gastrointestinal (GI) manifestation of systemic sclerosis (SSc) suggests a possible GI microbiota engagement in the pathophysiology and/or progression of SSc. Previous studies have revealed dysbiosis among Caucasian SSc patients. This study extends these findings to Asian SSc patients. METHODS: Adult SSc patients, stratified according to 1) on immunosuppressive (On-IS) drugs or 2) no immunosuppressive drugs (No-IS), and age-and-sex-matched healthy controls (HC) were recruited. Metagenomic sequencing of stool DNA was compared between SSc patients and HC, and between SSc (On-IS) and (No-IS) patients. Alpha and beta-diversity, taxonomic and functional profiling were evaluated. RESULTS: Twenty-three female SSc patients (12 On-IS; 11 No-IS; 5 diffuse and 18 limited SSc subtype) and 19 female HC, with median age of 54 years and 56 years, respectively, were recruited. Median SSc disease duration was 3.3 years. Alpha diversity was significantly higher in SSc versus HC (p=0.014) and in SSc (No-IS) versus HC (p=0.006). There was no significant difference in beta diversity between SSc and HC (p=0.307). At the phyla level, there were significantly increased abundance of Firmicutes and Actinobacteria in SSc versus HC, and reduced abundance of Bacteroidetes (all p<0.001). At the species level, there were significantly increased abundance of several Lactobacillus, Bifidobacterium, and Coprococcus species in SSc, and increased abundance of Odoribacter, Bacteroides and Prevotella species in HC. KEGG pathway analysis demonstrated distinct differences between SSc versus HC, and between SSc (No-IS) and SSc (On-IS). CONCLUSIONS: Using metagenomic sequencing, our study further underlines distinct alterations in microbiota profiling among Asian SSc patients.

Patient-defined flares and disease activity worsening in 222 patients with psoriatic arthritis from 14 countries.

OBJECTIVES: To explore patient-defined flares in psoriatic arthritis (PsA), compared to an increase in disease activity in psoriatic arthritis (DAPSA) and to analyze the validity of a patient-reported flare question. METHODS: ReFlap (NCT03119805) was a longitudinal study in 14 countries of consecutive patients with definite PsA. Patients were seen twice in the context of usual care, 4.5±2.2 months apart. Flares were reported by patients and physicians at the second visit using a single question. DAPSA worsening was defined as a change to a higher DAPSA category. Agreement between the definitions of worsening was calculated by prevalence adjusted bias adjusted kappa (PABAK). Validity of patient-reported flare was assessed by comparing patients with versus without flare and transition to flares. RESULTS: In 222 patients, mean disease duration 10.8±8.3 years, 127 (58.8%) males: disease activity was low (mean DAPSA 11.5±14.0); 63.3% received a bDMARD. Patient-reported flares between the 2 visits were seen in 27% patients (for these patients, mean 2.2±3.7 flares per patient, mean duration 12.6±21.0 days per flare). Physician- reported flares were seen in 17.6% and worsening in DAPSA in 40.1% of patients. Agreement between definitions was moderate (PABAK=0.32-0.59). Patients in flare had significantly more active disease than patients not in flare for all outcomes (all P<0.001). At the patient-level, transition to flare state was associated to a worsening in disease activity and impact outcomes. CONCLUSIONS: Patient flares were frequent and were associated with active and symptomatic disease. These findings provide preliminary validation for patient-reported flares in PsA.

Efficacy and safety of colchicine for the treatment of osteoarthritis: a systematic review and meta-analysis of intervention trials.

OBJECTIVE: Colchicine, an approved treatment for gout, has been trialed in many diseases including osteoarthritis (OA) due to its anti-inflammatory effects. However, its efficacy and safety remain unclear in OA. This systematic review and meta-analysis evaluated the efficacy and safety of colchicine for the treatment of OA. METHODS: PubMed, Web of Science, Scopus, and Cochrane Central were searched from inception through September 2022. Two reviewers independently screened for randomized controlled trials (RCTs) comparing colchicine with placebo or other active comparators for the treatment of OA (knee, hand, or hip OA), extracted data, and performed Cochrane risk of bias assessments. RESULT: Nine RCTs for the knee OA and one for the hand OA were identified, consisting of 847 patients (429 in colchicine arms, 409 in control arms). The studies were conducted between 2002 and 2021 with follow-up periods ranging from 2 to 12 months, in India, Iran, Turkey, Australia, Singapore, and Iraq. Moderate-quality evidence showed no clinically important pain reduction with colchicine compared to control (standardized mean difference [SMD], 0.17; 95% confidence interval [CI], - 0.55, 0.22). Moderate-quality evidence showed no improvement in function with colchicine compared to control in knee OA patients (SMD, - 0.37; 95% CI, - 0.87, 0.13). Colchicine showed an acceptable safety profile with AEs/SAEs comparable to control. CONCLUSION: Current evidence does not suggest a benefit of colchicine in reducing pain and improving physical function in the overall cohort of hand/knee OA patients. Future trials should focus on the subgroups of OA patients with local or systemic inflammation and/or mineralization who might benefit from colchicine.

Post-mRNA vaccine flares in autoimmune inflammatory rheumatic diseases: Results from the COronavirus National Vaccine registry for ImmuNe diseases SINGapore (CONVIN-SING).

BACKGROUND: Studies of flares of autoimmune inflammatory rheumatic diseases (AIIRD) after COVID-19 mRNA vaccination are limited by small sample size, short follow up or at risk of selection bias. METHODS: A national retrospective cohort study of consecutive AIIRD patients ≥12 years old, across 8 hospitals who received at least one dose of a COVID-19 mRNA vaccine. Patients were included from the date of 1st vaccine dose and censored at the time of flare or on the date of the clinic visit at least 3 months from cohort entry, whichever came first. Predictors of flare were determined by Cox proportional hazards analysis. FINDINGS: 4627 patients (73% Chinese, 71% female) of median (IQR) age 61 (48, 70) years were included; 42% Rheumatoid arthritis, 14% Systemic lupus erythematosus and 11% Psoriatic arthritis. 47% were in remission, 41% low disease activity, 10% moderate disease activity and 1% in high disease activity. 18% patients flared, of which 11.7% were within the 3-month period of interest. 11.8% patients improved. Median (IQR) time-to-flare was 60 (30, 114) days. 25% flares were self-limiting, 61% mild-moderate and 14% severe. Older patients (53-65 years and >66 years) had a lower risk of flare [HR 0.6 (95% CI 0.5-0.8) and 0.7 (0.6-0.8) respectively]. Patients with inflammatory arthritis and with active disease had a higher risk of flare [HR 1.5 (1.2-2.0) and 1.4 (1.2-1.6), respectively]. Treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), immunosuppression and prednisolone was also associated with an increased risk of flare [HR 1.5 (1.1-2), 1.2 (1.1-1.4) and 1.5 (1.2-1.8) for prednisolone ≤7.5 mg respectively]. INTERPRETATION: There was a moderately high rate of AIIRD flares after mRNA vaccination but also improvement in several patients. Severe flares and hospitalisation were rare. Thus, vaccination remains safe and highly recommended.

Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study

Abstract Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.