OBJECTIVE:To evaluate the efficacy, safety, and cost-effectiveness of tofacitinib (TOFA) monotherapy vs methotrexate (MTX) with glucocorticoid bridging in disease-modifying antirheumatic drug-naive patients with rheumatoid arthritis (RA). METHODS:In this open-label randomized controlled trial conducted from July 1, 2021, to December 31, 2023, we enrolled patients with moderate to high RA disease activity to receive TOFA (5 mg twice daily) or MTX (10 to 20 mg weekly with a single intramuscular betamethasone injection) in a 1:1 ratio. The primary end point was the proportion achieving clinical improvement at 3 months (>50% reduction in Simplified Disease Activity Index [SDAI] or absolute SDAI decrease ≥10 points). Secondary outcomes included remission or low disease activity rates, disease activity score changes, adverse events, and cost-effectiveness analysis. RESULTS:There were 116 patients enrolled, 57 in the TOFA group and 59 in the MTX group. The TOFA group demonstrated significant clinical improvement rates compared with the MTX group at month 3 (94.1% vs 75%; P=.02). The TOFA group demonstrated significantly greater reductions in all disease activity scores at month 3, including SDAI (15.7 [9.2 to 26.9] vs 8.9 [5.1 to 20.5]; P=.02), Clinical Disease Activity Index (14.5 [7.0 to 16.0] vs 7.3 [4.0 to 16.3]; P=.02), Disease Activity Score 28-C-reactive protein (1.7 [1.1 to 2.5] vs 1.2 [0.5 to 2.0]; P=.02), and Disease Activity Score 28-erythrocyte sedimentation rate (2.2 [1.5 to 3.3] vs 1.7 [0.7 to 2.4]; P=.02). The safety profiles were similar between the groups. Tofacitinib exhibited superior cost-effectiveness compared with MTX combined with betamethasone. CONCLUSION:In disease-modifying antirheumatic drug-naive patients with RA, TOFA monotherapy showed superior early efficacy compared with MTX plus glucocorticoid bridging, with better cost-effectiveness and comparable safety, supporting TOFA as a potential first-line bridging option. TRIAL REGISTRATION:ChiCTR2100048185.

To assess the knowledge, attitudes, and practices (KAP) regarding herpes zoster (HZ) and its vaccination among rheumatologists in China. A nationwide cross-sectional survey was conducted between April 1 and May 31, 2025, using the Questionnaire Star online platform. The questionnaire assessed sociodemographic characteristics, knowledge of HZ and its vaccine (via a 13-item scale), attitudes and behaviors regarding vaccination, and willingness to disseminate information. Ordinal logistic regression was applied to identify associated factors of knowledge scores, while subgroup analyses were conducted to evaluate attitude-related factors. A total of 1,772 rheumatologists from a wide range of provinces participated (mean age: 41.4 y; 67.3% female). Regarding professional background, most held a master's degree (44.1%), followed by a bachelor's (38.9%) and doctoral degree (17.0%). Clinical titles were distributed as associate chief (31.3%), chief (26.4%), attending (26.2%), and junior physicians (16.0%). The median knowledge score was 7 (IQR: 6-9). Multivariable analysis revealed that higher regional GDP per capita (β = 0.020, p = .040), advanced education (β = 0.234, p < .001), and greater clinical seniority (β = 0.296, p < .001) were independently associated with higher knowledge scores. Clinically, physicians expressed significant concern primarily in three areas: HZ's potential to interfere with the underlying autoimmune inflammatory rheumatic diseases (AIIRDs) (89.0%), HZ-related complications (81.5%), and deterioration of patient quality of life (73.0%). Notably, 65.6% of respondents were concerned about all three aspects simultaneously. Regarding vaccination attitudes, 96.4% of respondents reported conditional support for vaccinating patients with AIIRDs, contingent upon pre-vaccination risk assessment and adherence to recommended protocols. Additionally, 80.0% favored prioritizing recombinant vaccines. Subgroup analyses indicated that higher clinical seniority was significantly associated with more supportive attitudes (p < .001). In clinical practice, 76.5% of physicians reported actively recommending HZ vaccination, although several barriers remained. The main reasons for not recommending included limited consultation time (52.2%), perception of low HZ incidence (42.8%), and lack of patient concern (31.3%). Targeted education and strengthened rheumatologist-led counseling may help address existing barriers, particularly among junior physicians in under-resourced settings. Such measures could contribute to improving HZ vaccination uptake and protection in patients with AIIRDs.

Impaired renal urate excretion is a major mechanism underlying hyperuricemia and gout, with urate transporter 1 (URAT1), encoded by SLC22A12, playing a central role in proximal tubular urate reabsorption. This review summarizes the biological relevance of URAT1, the pharmacological evolution of URAT1 inhibitors, and their clinical implications in urate-lowering therapy. Evidence from transporter biology, structural pharmacology, pharmacokinetic and pharmacodynamic studies, and clinical trials was narratively synthesized. URAT1 inhibitors lower serum urate by blocking renal tubular urate reabsorption and increasing urinary urate excretion, providing a mechanism complementary to xanthine oxidase inhibition. Early uricosuric agents established the clinical value of this approach but are limited by non-selective transporter inhibition, tolerability concerns, drug–drug interactions, and organ-specific safety issues. Newer selective URAT1 inhibitors have been developed to improve transporter selectivity, pharmacodynamic precision, and clinical usability. Current evidence supports selective URAT1 inhibition as an effective strategy for achieving serum urate targets, particularly in underexcretion-type hyperuricemia, while renal monitoring and prevention of uric acid stone formation remain important. Emerging agents may further expand treatment options, but long-term renal, hepatic, and cardiovascular safety require further validation. Overall, URAT1 inhibition represents a rational and increasingly precise therapeutic strategy for hyperuricemia and gout, with future research needed to define its long-term outcomes, comparative effectiveness, pharmacogenomic predictors, and broader cardio-renal-metabolic implications.

Systemic lupus erythematosus (SLE) lacks sensitive biomarkers for early detection and longitudinal monitoring. Despite the diagnostic potential of IFI44L promoter hypomethylation, its dynamics across the clinical spectrum, ranging from pre-clinical stages to treatment response, remain poorly characterized. This study investigated IFI44L methylation across the SLE continuum to evaluate its performance in early diagnosis, disease activity assessment, and monitoring therapeutic response. In this cross-sectional study incorporating a longitudinal component, IFI44L promoter methylation was quantified by methylation-sensitive high-resolution melting analysis in 566 participants: healthy controls (HC, n = 106), first-degree relatives of SLE patients (at-risk, n = 27), incomplete lupus erythematosus (ILE, n = 68), classified SLE (active, n = 124; stable, n = 62), and an independent validation cohort of patients with other connective tissue diseases (CTDs, n = 179). Differences between groups were analyzed using non-parametric tests. ROC curves, Spearman’s correlation, and Wilcoxon signed-rank tests were employed to assess diagnostic performance, clinical associations, and treatment response, respectively. IFI44L promoter methylation exhibited a stepwise decline across the SLE continuum, with the highest levels in HCs and the lowest in active SLE. Hypomethylation (defined as <0.25) was present in 18.5

Despite the European Alliance of Associations for Rheumatology (EULAR) recommendation to minimize glucocorticoid (GC) use in systemic lupus erythematosus (SLE), prospective data quantifying toxicity across low-dose ranges are lacking. This study aimed to assess toxicity using the GC toxicity index (GTI) in SLE patients and compare toxicity profiles among dose-defined subgroups. Patients from the STAR cohort (May 2023–May 2024) were prospectively followed up for 1 year. Stratified by average daily prednisone (PDN) dose, toxicity was assessed using GTI comprising the aggregate improvement score (AIS) and the cumulative worsening score (CWS) at baseline and 1 year. Three pre-planned stepwise comparisons used dose thresholds of 7.5 mg, 5 mg, and 2.5 mg, with a Bonferroni-corrected significance level of P < 0.0167 (α = 0.05/3). Quantile regression evaluated the association between average daily PDN dose and CWS/AIS. Of 302 patients, the PDN ≤ 7.5 mg/day group (n = 223) showed statistically lower median CWS [0 (IQR 0–19) vs. 48 (IQR 19–84), P < 0.001] and AIS [0 (IQR − 19–10) vs. 40 (IQR 9–74), P < 0.001] compared to the PDN > 7.5 mg/day group (n = 79). Within the low-dose group, patients with 5 < PDN ≤ 7.5 mg/day (n = 52) exhibited higher median CWS [10.5 (IQR 0–29) vs. 0 (IQR 0–19), P = 0.002] and wider AIS interquartile range [0 (IQR − 18.75–29) vs. 0 (IQR − 20–0), P = 0.010] than the PDN ≤ 5 mg/day subgroup (n = 171). No significant differences in CWS or AIS were observed between the PDN ≤ 2.5 mg/day (n = 90) and 2.5 < PDN ≤ 5 mg/day (n = 81) subgroups. Quantile regression indicated that each 1 mg/day increase in PDN dose raised median CWS by 3.33 points and median AIS by 3.42 points. To our knowledge, this study provided the first prospective and quantitative evidence using the GTI to demonstrate that PDN dose reduction to ≤ 5 mg/day was linked to reduced toxicity. Moreover, we found that no dose was entirely safe, which strongly supported the EULAR strategy of rigorous GC minimization.

Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus (SLE). We sought to evaluate treatment patterns, treat-to-target state attainment, and outcomes of patients with active LN on non-biologic, conventional therapy, in a large real-world cohort from the Asia–Pacific region. Adult patients enrolled in a multinational lupus cohort were studied for evidence of active LN, defined based on the SLE Disease Activity Index-2000 (SLEDAI-2K)-proteinuria threshold (> 0.5 g/24 h or > 0.05g/mmol), ≥ 2 visits of data, and no exposure to biologics. The subset of these patients who had kidney biopsy-confirmed LN was retrospectively determined. Attainment of treatment goals, including modified versions of complete renal response (mCRR) and primary efficacy renal response (mPERR), lupus low disease activity state (LLDAS) and DORIS remission (REM), and organ damage accrual, were assessed over time following the first visit with proteinuria. One thousand one hundred eighty patients were studied for a median 2.7 [IQR 1.0, 5.0] years, 435 (37

Objectives:To integrate evidence from randomized controlled trials (RCTs) comparing subcutaneous (SC) and oral methotrexate (MTX) for rheumatoid arthritis (RA) to provide optimal clinical treatment strategies. Methods:This meta-analysis conducted comprehensive search of PubMed, Web of Science, Embase and Cochrane Library, retrieving all relevant RCTs published up to June 18, 2025. Random-effects models were utilized to calculate the relative risk (RR), mean difference (MD) and their 95% confidence intervals (CIs), to evaluate efficacy and safety between subcutaneous injections and oral administration of MTX. Results:A total of 1,034 articles were retrieved, and 9 RCTs that met the criteria were ultimately included, involving 974 RA patients in total. In the primary random-effects analyses, compared to oral MTX, subcutaneous MTX increased the ACR20 response rate (RR = 1.15; 95%CI: 1.05, 1.25), increased the ACR50 response rate (RR = 1.14; 95%CI: 1.01, 1.29), and reduced the incidence of gastrointestinal (GI)-related adverse event (AE) (RR = 0.58; 95%CI: 0.40, 0.83) and diarrhea (RR = 0.42; 95%CI: 0.21, 0.84). Fixed-effect sensitivity analyses supported the ACR20 and GI-related safety findings, but the ACR50 result was attenuated. Subcutaneous MTX did not show statistically significant differences in ACR70 response rate, DAS28-ESR score, bioavailability area under the curve, Cmax, or the incidence of other AE. Conclusion:Compared with oral administration, subcutaneous MTX was associated with a higher ACR20 response and lower GI-related AE and diarrhea in the primary random-effects analyses. These findings suggested that subcutaneous MTX may be an effective and generally well-tolerated option, particularly for patients with inadequate response or poor gastrointestinal tolerability to oral MTX, while evidence for ACR50, ACR70, DAS28-ESR and bioavailability remains less certain.

[Background and Objectives] Women with autoimmune inflammatory rheumatic diseases (AIIRDs) are more vulnerable to human papillomavirus (HPV) infection and HPV-related cervical cancers, however, the HPV screening and vaccination rate was low. We conducted a real-world survey to evaluate the awareness and status of HPV vaccination in Chinese AIIRDs patients. [Methods] Female patients with AIIRDs aged ≥ 9 years were enrolled between 1 April 2024 and 31 Aug 2024. Eligible participants completed a predefined 41-item questionnaire, which was distributed via social media invitations and in-person recruitment at outpatient clinics. We evaluated the demographics, rheumatic disease history, awareness of HPV infection and vaccination, HPV testing and vaccination status and willingness to receive HPV vaccine These factors were then compared between SLE and RA patients. [Results] A total of 562 participants with a median age of 34.9 (IQR 29.7–42.6) years completed the questionnaires. The awareness rates of HPV infection and vaccination were 82.0% and 85.9%, respectively. However, only 69.2% participants recognized the increased risk of cervical cancer associated with HPV, and just 52.3% had undergone cervical cancer screening in the past 5 years. Although 72.2% expressed willingness to receive the HPV vaccine, the actual vaccination rate was only 23.0%. Among the respondents, there were 334 SLE patients and 98 RA patients. Compared to RA patients, SLE patients were younger, had higher awareness of HPV vaccination, but a lower vaccination rate. [Conclusion] Patients with AIIRDs, SLE in particular, demonstrate high awareness of HPV infection and vaccination, as well as strong willingness to receive HPV vaccine. However, cervical cancer screening and actual HPV vaccination rates remain low.

Objective While guidelines advocate renin-angiotensin system inhibitors (RASi) for renoprotection in lupus nephritis (LN), evidence is largely extrapolated from non-lupus populations. Evidence specifically evaluating RASi efficacy during the intensive induction phase of active LN remains scarce. This study aimed to evaluate the real-world impact of adding RASi to standard induction therapy on renal remission and glucocorticoid tapering in LN. Methods This retrospective cohort study used data from the STAR (Treat-SLE-to-Target) registry. Patients receiving ≥3 months of continuous RASi during induction were classified as RASi, while those without RASi exposure during follow-up were classified as non-RASi. Propensity score overlap weighting was applied to balance baseline characteristics. The primary endpoints were rates of complete renal remission (CRR) at 12 months. Secondary endpoints included total renal remission (TRR), the magnitude and rate of proteinuria reduction and glucocorticoid dosage. Results Among 314 patients, 220 received RASi and 94 did not. The RASi group had higher baseline 24-hour urinary protein and hypertension prevalence. After weighting, characteristics were balanced. Weighted analyses showed no significant difference in CRR at 12 months (58.7% vs 64.7%, p=0.428) or 6 months (43.1% vs 53.4%, p=0.169). Conversely, 6-month TRR was significantly lower in the RASi group (59.0% vs 76.8%, p=0.026). Proteinuria percentage reduction was comparable between groups, and RASi use was not associated with accelerated glucocorticoid tapering or more rapid decline in disease activity. Multivariable analysis identified LN at SLE onset and baseline pyuria as independent predictors of CRR, but not RASi usage. Conclusion Adding RASi to standard induction therapy provided no additive benefit for renal remission or proteinuria reduction within the first 12 months nor did it facilitate glucocorticoid tapering. The haemodynamic antiproteinuric effects of RASi appear overshadowed by potent anti-inflammatory treatment during active LN.

OBJECTIVES:This study aimed to evaluate the efficacy and safety of mufemilast, a novel small-molecule selective phosphodiesterase 4 (PDE4) inhibitor, in patients with Behçet's syndrome (BS). METHODS:Patients diagnosed with BS according to the International Diagnostic (Classification) Criteria for Behçet's Disease 2013 and with active oral ulcers were eligible. Patients were randomly assigned to mufemilast (45 mg or 60 mg) or placebo, administered orally twice daily for 12 weeks. The primary endpoint was the area under the curve (AUC) for the number of oral ulcers from baseline to week 12. Safety was measured in all patients who received at least 1 dose of the study drug (ClinicalTrials: NCT04609397). RESULTS:Ninety patients were randomly assigned to the mufemilast 45 mg, 60 mg, or placebo groups (29, 31, and 30, respectively). The least-squares mean difference in AUC0-12 for oral ulcers between the 45 mg and 60 mg groups and the placebo was -104.8 (95% CI, -156.3 to -53.2; P < .001) and -142.5 (95% CI, -192.4 to -92.7; P < .001), respectively. The visual analogue pain scores and time to ulcer-free remission were significantly improved with mufemilast (P < .001). PDE4-related side effects were transient and resolved spontaneously, and discontinuation rates were low (7% for 45 mg, 7% for 60 mg, and 3% for placebo). No serious adverse events were reported related to the drug. CONCLUSIONS:Among patients with oral ulcers associated with BS, mufemilast significantly reduced the number of oral ulcers, improved pain scores, and induced significantly more ulcer-free remissions compared with placebo, with an acceptable safety profile.

OBJECTIVES:After the first tumour necrosis factor inhibitor (TNFi) failure, patients with rheumatoid arthritis (RA) often cycle to a second; however, switching mechanisms of action has been postulated to improve outcomes. The ongoing SELECT-SWITCH trial compared upadacitinib with adalimumab for active RA after first TNFi failure at 12 weeks. METHODS:Patients with inadequate response or intolerance to 1 nonadalimumab TNFi receiving stable methotrexate were randomised (1:1) to 15 mg once daily upadacitinib or 40 mg every-other-weekly adalimumab. The primary endpoint was achieving superiority in Disease Activity Score 28 (DAS28)-C-reactive protein (CRP) ≤3.2 at week 12. Ranked secondary endpoints (week 12, superiority) were (1) achieving ≥50% improvement in American College of Rheumatology response criteria (ACR50); (2) achieving DAS28-CRP <2.6; change from baseline in (3) DAS28-CRP; (4) pain; (5) Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS:Overall, 492 patients were randomised. Baseline characteristics were balanced between groups. Week 12 DAS28-CRP ≤3.2 response was superior with upadacitinib (43.3%) vs adalimumab (22.4%; difference, 21.0% [95% CI: 12.9-29.1]; P < .0001) as were ACR50 (38.2% vs 26.8% [P = .0068]), DAS28-CRP <2.6 (28.4% vs 14.5%; P = .0002), mean changes in DAS28-CRP (-2.432 vs -1.840; P < .0001) and pain (-3.165 vs -2.373; P = .0005), but not in HAQ-DI (-0.523 vs -0.496; P = .5849). Safety was comparable between treatments. CONCLUSIONS:The primary endpoint of the SELECT-SWITCH trial was met, with a higher percentage of patients with active RA who switched to upadacitinib after first TNFi failure achieving DAS28-CRP ≤3.2 at 12 weeks than those cycling to a second TNFi, adalimumab, with generally similar safety profiles. CLINICALTRIAL: GOV IDENTIFIER:NCT05814627.

OBJECTIVES:To determine the prevalence and predictive correlates of arthritis and joint damage in systemic lupus erythematosus (SLE) patients in the Asia-Pacific Lupus Collaboration (APLC) cohort, and to determine their impact on health-related quality of life (HRQoL). METHODS:SLE patient data (2013-2020) were collected from the prospective multinational APLC cohort. We defined arthritis according to the SLE Disease Assessment Index (SLEDAI-2K) definition of persistent arthritis as arthritis in ≥2 consecutive visits, and joint damage according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) definition (deforming or erosive arthritis). HRQoL was measured by Short Form Survey (SF36). Descriptive statistics, univariable and multivariable Cox hazard models, and Kaplan-Meier analyses were performed. RESULTS:During median 2.5 (1.0-5.1) years of follow-up, 803/4106 (19.6%) patients had arthritis at least once, and 18/3383 (0.53%) accrued joint damage. Patients with arthritis were more likely to be female, Caucasian, current smokers at enrolment, and less like to have tertiary education; they also had higher overall disease activity, and lower physical and mental HRQoL. Kaplan-Meier analysis demonstrated that joint damage was more likely in patients with arthritis. Persistent arthritis and longer follow-up were risk factors for joint damage accrual; being from high-income countries was protective. Patients with joint damage also had worse physical HRQoL. CONCLUSION:Arthritis in the APLC cohort was infrequent compared with other cohorts and was associated with smoking, higher overall disease activity, and damage accrual across multiple domains. Presence of arthritis significantly impacted physical and mental HRQoL. Joint damage was strongly predicted by persistent arthritis.

Chimeric antigen receptor (CAR) T-cell therapy, a transformative breakthrough originally pioneered in oncology, is being successfully repurposed for the treatment of refractory autoimmune rheumatic diseases (ARDs). By enabling profound depletion of pathogenic B cells—a central driver in conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIM)—CAR-T offers a promising therapeutic strategy for patients who have failed conventional therapies. Preliminary clinical evidence from early-phase trials indicates encouraging short-term efficacy across these ARDs. In SLE, treatment with CD19-directed CAR-T has been associated with high rates of lupus low disease activity state and a drug-free remission in a majority of patients. In SSc, CAR-T effectively suppresses inflammatory activity, although established fibrosis often requires continued adjunctive therapy. Promising clinical responses have also been observed in refractory IIM. The short-term safety profile appears favorable, with cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome being predominantly low-grade and manageable. Nevertheless, significant challenges remain. Key knowledge gaps include the long-term durability of responses, the patterns and functional competence of B-cell reconstitution, potential risks of secondary malignancies, and the substantial economic burden of current autologous platforms. Future translation efforts should focus on optimizing patient selection, developing next-generation CAR constructs (including allogeneic “off-the-shelf” products), exploring rational combination strategies, and establishing standardized outcome measures through larger prospective studies with extended follow-up. If validated in rigorous clinical development, CAR-T cell therapy may offer a novel and potent treatment option for carefully selected patients with severe, refractory autoimmune rheumatic diseases.

BACKGROUND:Factors associated with the risk of difficult-to-treat rheumatoid arthritis remain incompletely understood. We aimed to quantify the associations between key lifestyle factors, comorbidities, and difficult-to-treat rheumatoid arthritis risk. METHODS:In this systematic review and meta-analysis we systematically searched PubMed, Embase, and Cochrane Library from Jan 1, 2021, to Sept 1, 2025, for observational studies examining predefined lifestyle factors and comorbidities in relation to difficult-to-treat rheumatoid arthritis, as defined by the European Alliance of Associations for Rheumatology. Eligible studies were required to include adult rheumatoid arthritis populations with validated criteria, apply the European Alliance of Associations for Rheumatology definition of difficult-to-treat rheumatoid arthritis, and report adjusted effect estimates or sufficient data for calculation. Pooled odds ratios (ORs) or mean differences with 95% CIs were calculated using inverse-variance methods with random-effects models. Data were extracted independently by two reviewers using a standardised form, with methodological quality assessed using the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist. The primary outcome was the association between predefined lifestyle factors and comorbidities and difficult-to-treat rheumatoid arthritis. People with lived experience of rheumatoid arthritis were not involved in the study. The study was registered with PROSPERO (CRD420251148710). FINDINGS:21 studies (22 968 patients with rheumatoid arthritis, of which 2783 had difficult-to-treat rheumatoid arthritis) were included. Significant associations were observed for smoking history (OR 1·16, 95% CI 1·01 to 1·34; I2 =23%; 15 [71%] of 21 studies), obesity (1·38, 1·11 to 1·72; I2 =0%; eight [38%] studies), fibromyalgia (2·20, 1·64 to 2·96; I2 =43%; nine [43%] studies), and depression (1·74, 1·39 to 2·18; I2 =0%; nine [43%] studies). No associations were found for current smoking (1·23, 0·98 to 1·55; I2 =0%; nine [43%] studies), anxiety (1·45, 0·92 to 2·29; I2 =0%; four [19%] studies), and BMI as a continuous measure (mean difference 0·20 kg/m2; 95% CI -0·02 to 0·41; I2=12%; 11 [52%] studies). Analyses of socioeconomic status, osteoarthritis, and alcohol consumption were limited by few available studies. Risk of bias assessment indicated that most studies were of high quality, and no significant publication bias was detected. INTERPRETATION:This systematic review and meta-analysis identified that smoking, obesity, fibromyalgia, and depression are significantly associated with occurrence of difficult-to-treat rheumatoid arthritis. These findings support integrated management approaches that address both inflammatory pathways and risk factors in rheumatoid arthritis treatment strategies. FUNDING:National Natural Science Foundation of China.

OBJECTIVE:This research article aims to describe the prevalence, associations, and health-related quality of life (HRQoL) impact of mucocutaneous features of systemic lupus erythematosus (SLE). METHODS:Data from the Asia-Pacific Lupus Collaboration cohort were analyzed (2013-2021). Mucocutaneous activity (MC-A) items were rash, alopecia, and mucosal ulcers; were defined by the Systemic Lupus Erythematosus Disease Activity Index 2000; and were persistent if present for at least six months. Mucocutaneous damage (MC-D) items were chronic skin ulceration, scarring alopecia, and skin/panniculum scarring and were defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. HRQoL was measured by 36-Item Short Form Health Survey (SF-36) surveys. Multivariate logistic generalized estimating equation models were used to determine correlates of MC-A at each visit. Time-varying covariate survival models were used to determine predictors of MC-D. RESULTS:During a median of 2.5 (interquartile range 1.0-5.1) years' follow-up, 1,499 of 4,102 patients (36.5%) had MC-A (rash n = 1,055, alopecia n = 731, mucosal ulcers n = 352) and 606 of 3,655 patients (16.6%) had persistent MC-A. These patients were more likely to record worse mean mental (42.6 vs 44.8; P = 0.014) and physical component (41.1 vs 46.1; P < 0.001) SF-36 scores. Being White, smoking, serologic activity, vasculitis, myositis, serositis, nephritis, and neurologic/psychiatric features were correlates of MC-A. Of 3,647 patients, 157 (4.3%) accrued MC-D (skin/panniculum scarring n = 53, alopecia n = 98, ulceration n = 30). These patients had worse mean physical component (39.8 vs 46.0, P = 0.001) SF-36 scores and were more likely to be White with persistent MC-A. CONCLUSION:All mucocutaneous manifestations were associated with worse HRQoL. MC-A correlated with serologic and systemic disease activity burden in SLE. Persistent MC-A was associated with increased risk of MC-D, emphasizing the importance of early and effective treatment. Both MC-A and MC-D were more likely in White patients, suggesting ethnic and environmental impacts. Smoking was a potentially modifiable correlate of MC-A.