A phase 3, randomized, double-blind, active-controlled clinical trial to compare BAT1806/BIIB800, a tocilizumab biosimilar, with tocilizumab reference product in participants with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate: treatment period 2 analysis (week 24 to week 48).

BACKGROUND: Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24-48). METHODS: In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. RESULTS: Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. CONCLUSION: In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. TRIAL REGISTRATION: NCT03830203 and EudraCT 2018-002202-31.

Belimumab in early systemic lupus erythematosus: A propensity score matching analysis.

OBJECTIVE: This study aimed to evaluate the clinical efficacy of belimumab in patients with early systemic lupus erythematosus (SLE), defined as having a disease duration of less than 6 months. METHODS: We retrospectively identified patients with SLE in the early stage who received belimumab and standard of care (belimumab group) or standard of care alone (control group) since September 2020. Propensity score matching (PSM) was used to reduce potential bias. The primary endpoint was lupus low disease activity status (LLDAS) at weeks 12 and 24. The secondary endpoints were remission and the proportion of glucocorticoid dose tapering to 7.5 mg/day. The efficacy of belimumab in patients with lupus nephritis was also assessed. RESULTS: Out of 111 eligible patients, 16 patients in the belimumab group and 31 patients in the control group were identified by 1:2 PSM. At week 24, a significantly higher proportion of individuals achieved low disease activity state (LLDAS) in the belimumab group compared to the control group (56.3% vs. 19.4%, OR = 5.357, 95% CI = 1.417 to 20.260, p = 0.013). Furthermore, more patients in the belimumab group were reduced to low-dose glucocorticoid ( ≤ 7.5 mg/day) at week 24 (75.0% vs. 35.5%, OR = 5.182, 95%CI = 1.339 to 20.058, p = 0.017). Significant improvements in Patient Global Assessment scores were observed at Week 12 and 24 for those treated with belimumab compared to controls. In a subgroup analysis evaluating the efficacy of belimumab in patients with lupus nephritis, 42.9% of the seven individuals treated with belimumab achieved a complete renal response (CRR) by Week 24, and no instances of disease relapse were observed. CONCLUSIONS: In SLE patients with a disease duration of less than 6 months, belimumab treatment can promote LLDAS achievement and reduce glucocorticoid dose, leading to a better prognosis. Introducing belimumab in the early stage of SLE may be a beneficial decision.

Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

BACKGROUND: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

The additional role of anti-nucleosome antibodies in the prediction of renal damage in systemic lupus erythematosus based on CSTAR (XXV).

OBJECTIVES: The predominant determinant of an unfavorable prognosis among Systemic Lupus Erythematosus (SLE) patients resides in the irreversible organ damage. This prospective cohort study aimed to identify the additional value of anti-nucleosome antibodies on organ damage accumulation in SLE patients. METHODS: Based on the Chinese SLE Treatment and Research group (CSTAR) registry, demographic characteristics, autoantibodies profiles, and clinical manifestations were collected at baseline. Follow-up data were collected by reviewing clinical records. RESULTS: Of 2481 SLE patients with full follow-up data, 663 (26.7%) were anti-nucleosome antibodies positive and 1668 (68.0%) were anti-dsDNA antibodies positive. 764 (30.8%) patients developed new organ damage during a mean follow-up of 4.31 ± 2.60 years. At baseline, patients with positive anti-nucleosome antibodies have a higher rate of lupus nephritis (50.7% vs 36.2%, p < .001). According to the multivariable Cox regression analysis, both anti-nucleosome (HR = 1.30, 95% CI, 1.09-1.54, p < .001) and anti-dsDNA antibodies (HR=1.68, 95% CI, 1.38-2.05, p < .001) were associated with organ damage accumulation. Anti-nucleosome (HR = 2.51, 95% CI, 1.81-3.46, p < .001) and anti-dsDNA antibodies (HR = 1.69, 95% CI, 1.39-2.06, p < .001) were independent predictors for renal damage. Furthermore, the combination of the two antibodies can provide more accurate information about renal damage in overall SLE patients (HR = 3.19, 95% CI, 2.49-4.10, p < .001) and patients with lupus nephritis at baseline (HR = 2.86, 95% CI, 2.29-3.57, p < .001). CONCLUSION: Besides anti-dsDNA antibodies, anti-nucleosome antibodies can also provide information about organ damage accrual during follow-up. The ability of co-positivity of anti-nucleosome and anti-dsDNA antibodies in predicting renal damage may lead to additional benefits in the follow-up of these patients.

Serum proteome analysis identifies a potential biomarker for axial psoriatic arthritis.

BACKGROUND: To identify potential serum biomarkers for differentiating between axial psoriatic arthritis (axPsA) and peripheral psoriatic arthritis (pPsA). METHODS: Serum samples were collected from patients with PsA to create a biomarker discovery cohort and a verification cohort. Patients with PsA were classified into axial or peripheral subtypes based on imaging criteria. Untargeted proteomics technology was used in the discovery phase to screen for biomarkers, and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay (ELISA) in the verification phase. RESULTS: We identified 45 significantly differentially expressed proteins (DEPs) between axPsA (n = 20) and pPsA (n = 20) with liquid chromatography-mass spectrometry. Among these DEPs, serum pigment epithelium-derived factor (PEDF) was identified as a candidate biomarker using the Boruta algorithm and lasso regression. Results of ELISA further confirmed that the level of serum PEDF expression was significantly higher in axPsA (n = 37) than in pPsA (n = 51) at the verification cohort (37.9 ± 10.1 vs. 30.5 ± 8.9 µg/mL, p < 0.001). Receiver operating characteristics analysis showed that PEDF had an area under the curve (AUC) of 0.72. Serum PEDF was positively correlated with body mass index and C-reactive protein. Additionally, there was a tendency towards a positive correlation between PEDF and the Bath Ankylosing Spondylitis Disease Activity Index. CONCLUSIONS: This study provided a comprehensive characterization of the proteome in axPsA and pPsA and identified a candidate biomarker, PEDF, that may contribute to early diagnosis for axPsA.

Sex-specific differences in patients with psoriatic arthritis:a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR IV).

OBJECTIVES: To elucidate the sex-specific differences in demographic features, clinical characteristics, and quality of life in Chinese patients with psoriatic arthritis (PsA). METHODS: A total of 1,074 patients with PsA registered between December 2018 and June 2021 from the Chinese REgistry of Psoriatic ARthritis (CREPAR) cohort were selected. The baseline data on demographics, clinical characteristics, commonly used laboratory tests, comorbidities, and quality of life assessments were collected for this cross-sectional analysis. RESULTS: A total of 1,074 patients were included in this study, 585 (54.47%) of them were male and 489 (45.53%) were female. The age at PsA onset in male patients was earlier than that in female patients (38.10 ± 12.79 vs 40.37 ± 13.41, p = 0.005). For clinical characteristics, male patients presented with higher rates of axial involvement (43.89% vs 37.74%, p = 0.044) and nail involvement (66.15% vs 58.08%, p = 0.006), while female patients presented with higher rates of peripheral arthritis (89.57% vs 83.93%, p = 0.007). For laboratory tests, men presented with a higher percentage of HLA-B27 positivity than women (24.65% vs 16.70%, p = 0.002) and had higher levels of CRP (median 9.70 vs 5.65, p < 0.001). Regarding disease assessment indices, male patients scored higher in PASI and BASFI (median 5.00 vs 3.00, p = 0.007 and 1.80 vs 1.40, p = 0.012, respectively). No sex difference was found in rates of achieving remission. Factors associated with disease remission were also analyzed in both sexes. CONCLUSION: Demographic and clinical characteristics tend to vary between male and female patients with PsA. Male patients reported more functional limitations in daily life. Key Points • The demographic and clinical features vary greatly between male and female patients with PsA. • Male patients reported more functional burden in daily life as measured by BASFI.

Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial.

BACKGROUND: Biosimilars provide an opportunity to address unmet medical need by expanding access to biological treatments. This study aimed to show equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles of a proposed tocilizumab biosimilar BAT1806/BIIB800, to reference tocilizumab, in participants with rheumatoid arthritis with an inadequate response to methotrexate. METHODS: This phase 3, multicentre, randomised, double-blind, active-controlled, equivalence study comprised a 24-week initial treatment period (results reported here) and a 24-week secondary treatment period. Participants were recruited at 54 centres across five countries (China, Ukraine, Poland, Georgia, and Bulgaria). Patients with active rheumatoid arthritis with an inadequate response to methotrexate were randomly assigned (1:1:2) to receive reference tocilizumab up to week 48, or reference tocilizumab up to week 24 followed by BAT1806/BIIB800 up to week 48 (the two reference tocilizumab groups were analysed as a single group in this analysis), or BAT1806/BIIB800 up to week 48 (the BAT1806/BIIB800 group), administered by intravenous infusion once every 4 weeks at a starting dose of 8 mg/kg. The primary endpoint was the proportion of participants who had a 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 (for the European Medicines Agency [EMA]) or week 24 (for the US Food and Drug Administration [FDA] and China National Medical Products Administration [NMPA]) using prespecified equivalence margins (95% CI -14·5 to +14·5 [EMA], 90% CI -12·0 to +15·0 [FDA], and 95% CI -13·6 to +13·6 [NMPA]). The International Council for Harmonisation E9(R1) estimand framework, with strategies for addressing intercurrent events, was implemented for the efficacy evaluations with expected differences as per the predefined equivalence margins. This trial is registered at ClinicalTrials.gov (NCT03830203) and EudraCT (2018-002202-31), and is closed to new participants. FINDINGS: Between Dec 19, 2018, and Jan 5, 2021, we randomly assigned 621 participants: 309 to the reference tocilizumab group and 312 to the BAT1806/BIIB800 group. The mean age was 50·5 years (SD 12·0), 534 (86%) were women, 87 (14%) were men, and 368 (59%) were White. For the primary estimands, estimated ACR20 response rates were 64·8% in the reference tocilizumab group and 69·0% in the BAT1806/BIIB800 group (treatment difference 4·1% [95% CI -3·6 to 11·9]) at week 12, and 67·9% in the reference tocilizumab group and 69·9% in the BAT1806/BIIB800 group (treatment difference 1·9% [90% CI -4·0 to 7·9; 95% CI -5·2 to 9·1]) at week 24. All confidence intervals were contained within the predefined equivalence margins. Comparable pharmacokinetic and immunogenicity profiles were observed for the reference tocilizumab and BAT1806/BIIB800 groups. Adverse events were reported by 201 (65%) participants in the reference tocilizumab group and 206 (66%) in the BAT1806/BIIB800 group; 196 (63%) participants in the reference tocilizumab group and 201 (64%) participants in the BAT1806/BIIB800 group reported a treatment-emergent adverse event. Five participants had a fatal event (reference tocilizumab n=1; BAT1806/BIIB800 n=4). INTERPRETATION: BAT1806/BIIB800 showed equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles as reference tocilizumab. FUNDING: Bio-Thera Solutions and Biogen.

Development and external validation of a prediction model for venous thromboembolism in systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of venous thromboembolism (VTE). We conducted this study to develop a risk score algorithm for VTE in patients with SLE that provides individualised risk estimates. METHODS: We developed a clinical prediction model of VTE in 4502 patients with SLE based on the Chinese SLE Treatment and Research group cohort (CSTAR) from January 2009 to January 2020 and externally validated in 3780 patients with SLE in CSTAR from January 2020 to January 2022. Baseline data were obtained and VTE events were recorded during the follow-up. The prediction model was developed to predict VTE risk within 6 months in patients with SLE, using multivariate logistic regression and least absolute shrinkage and selection operator. SLE-VTE score and nomogram were established according to the model. RESULTS: A total of 4502 patients included in the development cohort, 135 had VTE events. The final prediction model (SLE-VTE score) included 11 variables: gender, age, body mass index, hyperlipidaemia, hypoalbuminaemia, C reactive protein, anti-ß2GPI antibodies, lupus anticoagulant, renal involvement, nervous system involvement and hydroxychloroquine, with area under the curve of 0.947 and 0.808 in the development (n=4502) and external validation cohort (n=3780), respectively. According to the net benefit and predicted probability thresholds, we recommend annual screening of VTE in high risk (≥1.03%) patients with SLE. CONCLUSION: Various factors are related to the occurrence of VTE in patients with SLE. The proposed SLE-VTE risk score can accurately predict the risk of VTE and help identify patients with SLE with a high risk of VTE who may benefit from thromboprophylaxis.

Efficacy and safety of Janus kinase inhibitors in systemic and cutaneous lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND: Janus kinase (JAK) inhibitors have been proven to be effective and safe in various autoimmune diseases. However, there is still a lack of comprehensive evidence regarding their efficacy and safety in systemic and cutaneous lupus erythematosus. METHODS: We searched for systemic and cutaneous lupus erythematosus patients who were treated with JAK inhibitors in PubMed, Embase, Web of Science, and the Cochrane Library until February 28, 2023. The quality of clinical trials was assessed using the Cochrane risk-of-bias tool. Meta-analysis was conducted when at least three studies had comparable measures of outcome. If meta-analysis was not feasible, a descriptive review was carried out. RESULTS: We included 30 studies, consisting of 10 randomized controlled trials and 20 case series or reports, with a total of 2,460 patients. JAK inhibitors were found to be more effective than placebo in systemic lupus erythematosus (SLE) based on the percentage of achieving SLE Responder Index (SRI)-4 response (RR = 1.18; 95% CI 1.07 to 1.31; p = 0.001), British Isles Lupus Assessment Group -based Composite Lupus Assessment (BICLA) response (RR = 1.16; 95% CI 1.02 to 1.31; p = 0.02), Lupus Low Disease Activity State (LLDAS) (RR = 1.28; 95% CI 1.07 to 1.54; p = 0.008), and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) remission of arthritis or rash (RR = 1.09; 95% CI 1.00 to 1.18; p = 0.04), particularly in treating musculoskeletal and mucocutaneous involvement. However, the effect of JAK inhibitors on cutaneous lupus erythematosus was uncertain. JAK inhibitors and placebo had a similar incidence of adverse events (RR = 1.01; 95% CI 0.97 to 1.04; p = 0.65). CONCLUSION: JAK inhibitors could be a potential treatment option for systemic and cutaneous lupus erythematosus, particularly in treating cutaneous and musculoskeletal lesions of SLE. JAK inhibitors had a safe profile.

Chinese Registry of Psoriatic Arthritis (CREPAR): I. Clinical characteristics of Chinese patients with psoriatic arthritis.

AIM: To describe the clinical characteristics of Chinese patients with psoriatic arthritis (PsA) using the data recorded in the Chinese Registry of Psoriatic Arthritis (CREPAR). METHODS: This is a cross-sectional study based on the CREPAR registry, which is a prospective registry founded in December 2018. Data regarding clinical characteristics and treatment of patients were collected during every visit. Data recorded at enrollment were extracted, analyzed, and compared with data in other registries or cohorts. RESULTS: A total of 1074 patients were registered from December 2018 to June 2021. Of these, 929 (86.5%) patients had a history of peripheral arthritis, and 844 patients (78.6%) had peripheral arthritis at enrollment, of which polyarthritis is the most common subtype. Axial involvement was present in 39.9% of patients, and 50 (4.7%) patients had axial involvement only. More than half of the patients (55.4%) had at least two musculoskeletal presentations at enrollment. The prevalence of low disease activity and remission according to DAPSA were 26.4% and 6.8%, respectively. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological DMARDs were used in 64.9% and 29.1% of patients, respectively. Among patients with different musculoskeletal presentations, patients with dactylitis had the highest proportion of nonsteroidal anti-inflammatory and csDMARD use. The proportion of patients receiving bDMARDs was highest in axial PsA. CONCLUSION: The CREPAR registry has provided information on Chinese patients with PsA. Compared with data in other registries or cohorts, the disease activity of patients in CREPAR was higher, and the proportion of bDMARD use was lower.

Consensus on targeted drug therapy for spondyloarthritis.

Spondyloarthritis (SpA) is a group of chronic inflammatory diseases that predominantly involve the spine and/or peripheral joints. The clinical manifestations of SpA are highly heterogenous and complicated with various comorbidities. SpA is a disabling disease and adversely affects the quality of life of patients. Many new medications that target cytokines or pathways specific for the pathogenesis of SpA have been developed and they are becoming increasingly important in the treatment of SpA. However, identifying the target patient population and standardizing the usage of these drugs are critical issues in the clinical application of these "targeted therapeutic drugs". Under the leadership of National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), managed by Peking Union Medical College Hospital, the "Consensus on targeted drug therapy for spondyloarthritis" has been developed in collaboration with the Rheumatology and Immunology Physicians Committee, Chinese Medical Doctors Association, Rheumatology and Immunology Professional Committee, Chinese Association of Rehabilitation Medicine, and Chinese Research Hospital Association Rheumatology and Immunology Professional Committee. This consensus has been developed with evidence-based methodology and has followed the international standard for consensus development.

Risk factors for avascular necrosis in patients with systemic lupus erythematosus: a multi-center cohort study of Chinese SLE Treatment and Research Group (CSTAR) Registry XXII.

BACKGROUND: Avascular necrosis is a common organ damage in SLE patients, which can influence patients' life quality. Conflicting results exist in risk factors of AVN in SLE patients. The aim of this study was to illustrate risk factors predicting the occurrence of avascular necrosis (AVN), also known as osteonecrosis, in systemic lupus erythematosus (SLE) patients in Chinese SLE Treatment and Research Group (CSTAR), a multi-center cohort of Chinese SLE patients. METHODS: SLE patients in CSTAR without existing AVN at registration were included. At least two follow-ups and an observation period of no less than 2 years for AVN event were required. Univariate and multivariate Cox regression analyses were used to evaluate risk factors for AVN in SLE patients. Coefficient B was transformed to risk score for the development of a risk stratification model. RESULTS: One hundred six (2.59%) of 4091 SLE patients were diagnosed AVN during follow-ups of no less than 2 years. Multi-variate Cox regression analysis suggested that SLE onset age ≤ 30 (HR 1.616, p 0.023), arthritis (HR 1.642, p 0.018), existing organ damage (SDI ≥ 1) at registration (HR 2.610, p < 0.001), positive anti-RNP (HR 1.709, p 0.006), and high glucocorticoid maximum daily dose at registration (HR 1.747, p 0.02) were independent risk factors. A risk stratification system was developed according to the risk factors, and patients were divided into high risk (3-6) and low risk (0-2). The AUC of 0.692 indicated moderate discrimination. The calibration curve in internal validation was drawn. CONCLUSION: Patients with SLE onset age ≤ 30, arthritis, existing organ damage (SDI ≥ 1) at registration, positive anti-RNP, and high glucocorticoid maximum daily dose at registration are at high risk for AVN and require attention.

Associations between family history of psoriatic disease and clinical characteristics on patients with psoriatic arthritis: a nationwide study from the Chinese Registry of Psoriatic Arthritis (CREPAR II).

OBJECTIVES: The study aimed to identify clinical characteristics in Chinese patients with psoriatic arthritis (PsA) with or without a family history of psoriasis and/or PsA. METHODS: Patients with PsA were recruited based on Chinese REgistry of Psoriatic ARthritis (CREPAR) between December 2018 and June 2021. The demographics, clinical information relating to PsA, laboratory variables and comorbidities were collected. The association between family history of psoriatic disease and clinical characteristics on PsA was analysed using logistic regression analysis. RESULTS: Among 1074 eligible patients with PsA, 313 (29.1%) had a family history of psoriasis and/or PsA. Compared with patients without a family history, notably, patients with a family history of psoriasis and/or PsA had an earlier age of onset of psoriasis and PsA, higher proportions of enthesitis and nail involvement, a higher prevalence of positive human leukocyte antigen-B27 (HLA-B27), lower disease activity score 28-erythrocyte sedimentation rate, higher proportions of hyperlipidaemia, lower proportions of hypertension and diabetes. Furthermore, after adjusting for confounding factors, logistic regression analysis demonstrated that a positive family history of psoriasis and/or PsA was associated with more females (OR 1.514, 95% CI 1.088-2.108, p=0.014), earlier age at psoriasis onset (OR 0.971, 95%CI 0.955-0.988, p=0.001), a higher prevalence of HLA-B27 (OR 1.625 95%CI 1.089-2.426, p=0.018), more presence of nail involvement (OR 1.424, 95%CI 1.007-2.013, p=0.046) and enthesitis (OR 1.393, 95%CI 1.005-1.930, p=0.046), a higher proportion of hyperlipidaemia (OR 2.550, 95%CI 1.506-4.317, p=0.001) in PsA patients. CONCLUSIONS: This was first nationwide study to characterize patients with and without a family history of psoriatic disease in China. The findings from the present study revealed that family history of psoriasis and/or PsA had greater effects on disease phenotypes of PsA, especially nail disease and enthesitis.

Enthesitis in patients with psoriatic arthritis: A nationwide data from the Chinese Registry of Psoriatic Arthritis (CREPAR).

BACKGROUND: The clinical features of enthesitis in patients with psoriatic arthritis (PsA) have been reported in some Western countries, but data in China are very limited. This study aimed to describe the characteristics of enthesitis in Chinese patients with PsA and compared them with those in other cohorts. METHODS: Patients with PsA enrolled in the Chinese Registry of Psoriatic Arthritis (CREPAR) (December 2018 to June 2021) were included. Data including demographics, clinical characteristics, disease activity measures, and treatment were collected at enrollment. Enthesitis was assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht ankylosing spondylitis enthesitis score (MASES), and Leeds enthesitis index (LEI) indices. A multivariable logistic model was used to identify factors related to enthesitis. We also compared our results with those of other cohorts. RESULTS: In total, 1074 PsA patients were included, 308 (28.7%) of whom had enthesitis. The average number of enthesitis was 3.3 ± 2.8 (range: 1.0-18.0). More than half of the patients (165, 53.6%) had one or two tender entheseal sites. Patients with enthesitis had an earlier age of onset for both psoriasis and arthritis, reported a higher proportion of PsA duration over 5 years, and had a higher percentage of axial involvement and greater disease activity. Multivariable logistic regression showed that axial involvement (odds ratio [OR] 2.21, 95% confidence interval [CI], 1.59-3.08; P <0.001), psoriasis area and severity index (PASI) (OR: 1.03, 95% CI: 1.01-1.04; P = 0.002), and disease activity score 28-C reactive protein (DAS28-CRP) (OR: 1.25, 95% CI: 1.01-1.55; P = 0.037) were associated with enthesitis. Compared with the results of other studies, Chinese patients with enthesitis had a younger age, lower body mass index (BMI), a higher rate of positive human leukocyte antigen (HLA)-B27, more frequent dactylitis, and a higher proportion of conventional synthetic disease-modifying antirheumatic drugs' (csDMARDs) use. CONCLUSIONS: Enthesitis is a common condition among Chinese patients with PsA. It is important to evaluate entheses in both peripheral and axial sites.

Efficacy and safety of Janus kinase inhibitors in patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of Janus kinase (JAK) inhibitors (Jakinibs) in the treatment of psoriasis and psoriatic arthritis (PsA). METHODS: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials on the efficacy and safety of Jakinibs in treating psoriasis and PsA from inception to July 2021. A systematic review and meta-analysis were performed to estimate pooled relative risk (RR) and 95% confidence interval (CI). RESULTS: Seventeen clinical trials (16 publications) comprising 6802 patients were included. All Jakinibs demonstrated significantly higher response rates compared with placebo (ACR20: RR 2.09, 95% CI 1.90-2.30; PASI75: RR 4.03, 95% CI 3.13-5.18). Within the subgroup analysis, the response rates defined by ACR20 were highest for filgotinib (RR 2.40, 95% CI 1.67-3.45), followed by upadacitinib, tofacitinib, and deucravacitinib. The proportion of patients achieving PASI75 response in the tofacitinib 10 mg twice daily group was significantly higher than that in the tofacitinib 5 mg group. Regarding safety, the incidence of adverse events (AEs) was significantly higher for Jakinibs compared with placebo (RR 1.17, 95% CI 1.11-1.23). Of note, a considerable increase in the risk of infections including upper respiratory tract and herpes zoster infection was observed among patients in the treatment group. For tofacitinib, upadacitinib, and filgotiniband, infection was the most prevalent AE. Moreover, AEs in the 10 mg tofacitinib group were higher than those in the 5 mg tofacitinib group. CONCLUSION: Jakinibs are efficacious interventions for the treatment of psoriasis and PsA, but they are associated with an increased risk of AEs when compared with placebo. The long-term efficacy and safety data require further evaluation. Key Points • This systematic review investigated and compared the efficacy and safety of different Jakinibs including the novel selective TYK2 inhibitors. • Jakinibs are efficacious interventions for the treatment of psoriasis and PsA. • A relatively higher dosing schedule of Jakinibs is associated with increased toxicity.

A multi-center, open-label, randomized study to explore efficacy and safety of baricitinib in active primary Sjogren's syndrome patients.

BACKGROUND: Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease involving multiple organ systems. The Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is a key pathway involving the pathogenesis of pSS. Baricitinib, a selective JAK1 and JAK2 inhibitor, has been approved for treatment of active rheumatoid arthritis and reported in treatment of some other autoimmune diseases including systemic lupus erythematosus. We have found that baricitinib might be effective and safe in pSS in a pilot study. However, there is no published clinical evidence of baricitinib in pSS. Hence, we conducted this randomized study to further explore the efficacy and safety of baricitinib in pSS. METHODS: This is a multi-center, prospective, open-label, randomized study to compare the efficacy of baricitinib + hydroxychloroquine (HCQ) with HCQ alone in pSS patients. We plan to involve 87 active pSS patients with European League Against Rheumatism pSS disease activity index (ESSDAI) ≥ 5 from eight different tertiary centers in China. Patients will be randomized (2:1) to receive baricitinib 4 mg per day + HCQ 400 mg per day or HCQ 400 mg per day alone. We will switch HCQ to baricitinib + HCQ if the patient in the latter group has no ESSDAI response at week 12. The final evaluation will be at week 24. The primary endpoint is the percentage of ESSDAI response, or minimal clinically important improvement (MCII), which was defined as an improvement of ESSDAI at least three points at week 12. The secondary endpoints include EULAR pSS patient-reported index (ESSPRI) response, change of Physician's Global Assessment (PGA) score, serological activity parameters, salivary gland function test, and focus score on labial salivary gland biopsy. DISCUSSION: This is the first randomized controlled study to evaluate the clinical efficacy and safety of baricitinib in pSS. We hope that the result of this study can provide more reliable evidence of the efficacy and safety of baricitinib in pSS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05016297. Registered on 19 Aug 2021.

Efficacy and safety of tofacitinib in Chinese patients with active psoriatic arthritis: a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVES: Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug. METHODS: Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). PRIMARY ENDPOINT: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout. RESULTS: The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p<0.0001). M3 ACR20/ACR70/PASI75 responses, and enthesitis and dactylitis resolution rates, were higher and HAQ-DI reduction was greater for tofacitinib 5 mg twice daily versus placebo. Incidence of adverse events (AEs)/serious AEs (M0-3): 68.4%/0%, tofacitinib 5 mg twice daily; 75.0%/4.4%, placebo. One death was reported with placebo→tofacitinib 5 mg twice daily (due to accident). One serious infection, non-serious herpes zoster, and lung cancer case each were reported with tofacitinib 5 mg twice daily; four serious infections and one non-serious herpes zoster case were reported with placebo→tofacitinib 5 mg twice daily (M0-6). No non-melanoma skin cancer, major adverse cardiovascular or thromboembolism events were reported. CONCLUSION: In Chinese patients with PsA, tofacitinib efficacy was greater than placebo (primary and secondary endpoints). Tofacitinib was well tolerated; safety outcomes were consistent with the established safety profile in PsA and other indications. TRIAL REGISTRATION NUMBER: NCT03486457.

Sex differences in systemic lupus erythematosus (SLE): an inception cohort of the Chinese SLE Treatment and Research Group (CSTAR) registry XVII.

BACKGROUND: The onset and clinical presentation of systemic lupus erythematosus (SLE) are sex-related. Few studies have investigated the distinctions in clinical characteristics and treatment preferences in male and female SLE patients in the initial cohort. This study aimed to improve the understanding of Chinese SLE patients by characterizing the different sexes of SLE patients in the inception cohort. METHODS: Based on the initial patient cohort established by the Chinese SLE Treatment and Research Group, a total of 8713 patients (795 men and 7918 women) with newly diagnosed SLE were enrolled between April 2009 and March 2021. Of these, 2900 patients (347 men and 2553 women) were eligible for lupus nephritis (LN). A cross-sectional analysis of the baseline demographic characteristics, clinical manifestations, laboratory parameters, organ damage, initial treatment regimens, and renal pathology classification was performed according to sex. RESULTS: In the SLE group, as compared to female patients, male patients had a later age of onset (male vs. female: 37.0 ±â€Š15.8 years vs. 35.1 ±â€Š13.7 years, P  = 0.006) and a higher SLE International Collaborative Clinic/American College of Rheumatology damage index score (male vs. female: 0.47 ±â€Š1.13 vs. 0.34 ±â€Š0.81, P  = 0.015), LN (male vs. female: 43.6% vs. 32.2%, P < 0.001), fever (male vs. female: 18.0% vs. 14.6%, P  = 0.010), thrombocytopenia (male vs. female: 21.4% vs. 18.5%, P  = 0.050), serositis (male vs. female: 14.7% vs. 11.7%, P  = 0.013), renal damage (male vs. female: 11.1% vs. 7.4%, P < 0.001), and treatment with cyclophosphamide (CYC) (P < 0.001). The frequency of leukopenia (male vs. female: 20.5% vs. 25.4%, P  = 0.002) and arthritis (male vs. female: 22.0% vs. 29.9%, P < 0.001) was less in male patients with SLE. In LN, no differences were observed in disease duration, SLE Disease Activity Index score, renal biopsy pathological typing, or 24-h urine protein quantification among the sexes. In comparisons with female patients with LN, male patients had later onset ages (P  = 0.026), high serum creatinine (P < 0.001), higher end-stage renal failure rates (P  = 0.002), musculoskeletal damage (P  = 0.023), cardiovascular impairment (P  = 0.009), and CYC use (P  = 0.001); while leukopenia (P  = 0.017), arthritis (P  = 0.014), and mycophenolate usage (P  = 0.013) rates were lower. CONCLUSIONS: Male SLE patients had more severe organ damage and a higher LN incidence compared with female SLE patients; therefore, they may require more aggressive initial treatment compared to female patients.