Risk of Malignancy and Tuberculosis of Biological and Targeted Drug in Patients With Spondyloarthritis: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objective: Concerns exist regarding the potential development of malignancy and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. We assessed the extent to which biologic therapy may increase the risk of malignancy and tuberculosis in patients with SpA by meta-analysis to derive estimates of sparse harmful events occurring in Randomized Controlled Trials (RCTs). Methods: A systematic literature search was conducted in PubMed, EMbase, Web of Science, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating the risk of sparse harmful events of biologic therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto OR for malignancy and tuberculosis in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using Cochrane Risk of Bias tool. Results: In total, 63 studies were included in this meta-analysis, and 83 patients and 7 patients developed malignancy and tuberculosis, respectively. Overall, the risk of malignancy and tuberculosis was increased in SpA patients treated with biologics compared to placebo (malignancy: Peto OR: 2.49, 95%CI: 1.61-3.87, p < 0.001; tuberculosis: Peto OR: 5.98, 95%CI: 1.29-27.76, p = 0.022). Remarkably, compared to placebo, there was higher risk of malignancy for IL-17 inhibitors (Peto OR: 3.68, 95%CI: 1.20-11.30, p = 0.023) and small molecule targeted drugs (Peto OR: 3.08, 95%CI: 1.37-6.90, p = 0.043) in peripheral SpA, and for TNF receptor-Fc fusion protein in axial SpA (Peto OR: 7.18, 95%CI: 1.21-42.69, p = 0.030). Besides, the risk of tuberculosis was higher for anti-TNFα antibody in axial SpA (Peto OR: 6.17, 95%CI: 1.03-37.13, p = 0.046). Conclusion: This meta-analysis showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and small molecule targeted drugs, a slightly increased risk of malignancy in TNF receptor-Fc fusion protein in axial SpA, and increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. These findings need to be validated by studies with larger population and longer follow-up.

Characteristics Associated with the Occurrence and Development of Acute Anterior Uveitis, Inflammatory Bowel Disease, and Psoriasis in Patients with Ankylosing Spondylitis: Data from the Chinese Ankylosing Spondylitis Prospective Imaging Cohort.

INTRODUCTION: This study aimed to determine the association between extra-articular manifestations (EAMs) and baseline characteristics of patients with ankylosing spondylitis (AS) and identify their potential risk factors in an observational cohort. METHODS: We analyzed the data of consecutive patients with AS obtained between April 2016 and May 2019 from the ongoing Chinese Ankylosing Spondylitis Prospective Imaging Cohort. RESULTS: Among the 1414 patients with AS, 23.1% had experienced EAMs at baseline. The prevalence rates of acute anterior uveitis (AAU), inflammatory bowel disease, and psoriasis among patients with AS were 16.7, 6.9, and 2.6%, respectively, and the prevalence of AAU increased significantly with the disease duration. Patients with comorbidity of AAU and psoriasis had Ankylosing Spondylitis Disease Activity Score (ASDAS) than patients without EAMs (2.16 ± 0.984 vs. 1.99 ± 0.956 [p = 0.025] and 2.36 ± 1.01 vs. 1.99 ± 0.96 [p = 0.025]). Among the 1087 patients with AS without EAMs at baseline, 98 developed EAMs during follow-up. Long disease duration (> 10 years) and high disease activity at baseline (ASDAS > 2.1) were associated with the risk of new-onset EAMs (hazard ratio [HR] [95% confidence interval, CI], 2.150 [1.229-3.762] and 2.896 [1.509-5.561], respectively) and new-onset AAU (HR [95% CI], 2.197 [1.325-3.642] and 3.717 [1.611-8.574], respectively). CONCLUSIONS: In Chinese patients with AS, patients with comorbidity of AAU and psoriasis had higher disease activity scores than patients without EAMs. Furthermore, the risk of AAU or combined EAMs increases with the duration of AS and appears to be associated with higher cumulative exposure to inflammation.

Tai Chi exercise can ameliorate physical and mental health of patients with knee osteoarthritis: systematic review and meta-analysis.

OBJECTIVE: To systematically review the effects of Tai Chi exercise as a nonpharmacological therapeutic strategy on the physical and mental health in individuals with knee osteoarthritis. DATA SOURCES: A systematic literature retrieval has been conducted in PubMed, Web of Science, EMbase, CENTRAL, OVID, CINAHL, Physiotherapy Evidence Database, Chinese Biomedical Database and China National Knowledge Infrastructure up to June 2020 to identify the relevant randomised controlled trials (RCTs). METHODS: Two authors assessed independently the risk of bias using the Cochrane Collaboration's tool. Standardised mean difference (SMD) and 95% CI were calculated and data were combined using the fixed or random-effect model. The strength of evidence was rated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A total of 16 RCTs involving 986 patients with knee osteoarthritis met the established inclusion criteria. The strength of evidence for the main outcomes was low or moderate. The systematic review illustrated the efficacy of Tai Chi exercise in treating and managing knee osteoarthritis. Patients' outcomes practising Tai Chi exercise were improved significantly, including pain (SMD = ‒0.69, 95%CI: ‒0.95 to ‒0.44, P < 0.001), stiffness (SMD = ‒0.59, 95%CI: ‒0.91 to ‒0.27, P < 0.001), physical function (SMD = ‒0.92, 95%CI: -1.16 to ‒0.69, P < 0.001), dynamic balance (SMD = 0.69, 95%CI: 0.38 to 0.99, P < 0.001), physiological and psychological health (SF-36 PCS: SMD = 0.48, 95%CI: 0.28 to 0.68, P < 0.001; SF-36 MCS: SMD = 0.26, 95%CI: 0.06 to 0.45, P = 0.01). No adverse events associated with Tai Chi exercise were reported. CONCLUSION: Tai Chi exercise was beneficial for ameliorating physical and mental health of patients with knee osteoarthritis and should be available as an alternative non-pharmacological therapy in rehabilitation programmes.

Add-On Effects of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs in Ankylosing Spondylitis: Data from a Real-World Registered Study in China.

BACKGROUND The aim of this study was to investigate the effects of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on patients with ankylosing spondylitis (AS) using real-world data, and to analyze patients' choices of csDMARDs and reasons for discontinuation. MATERIAL AND METHODS This observational study included 320 patients satisfying the modified New York criteria for AS. Patients were grouped according to medication: Group 1: 122 patients receiving non-steroidal anti-inflammatory drug (NSAID) monotherapy; Group 2: 198 patients receiving csDMARDs and NSAIDs. Patients were followed for 18 months at 6-month intervals. The change in AS Disease Activity Score and C-reactive protein (ASDAS-CRP) at each visit was the primary outcome. Secondary outcomes were based on validated disease activity questionnaires, clinical assessment, and acute-phase biomarkers (CRP and erythrocyte sedimentation rate [ESR]). Inter-group relationships were assessed across the 18-month follow-up period using generalized additive mixed models. RESULTS Sulfasalazine and thalidomide were the most commonly used csDMARDs, with cumulative use times of 8.9±4.1 months and 9.1±4.7 months, respectively. In Group 2, 56 patients discontinued or switched csDMARDs during the follow-up period, with lack of efficacy being the primary reason. The ASDAS-CRP was found to decrease significantly in both groups; however, improvements in many parameters (including ASDAS-CRP, disease activity questionnaires and ESR) were greater in Group 2. CONCLUSIONS Use of csDMARDs can improve disease activity in terms of ASDAS-CRP. The addition of csDMARDs may provide increased benefits compared with NSAID monotherapy, particularly in the reduction of AS disease activity, in the Chinese population.

Improvement of Disease Management and Cost Effectiveness in Chinese Patients with Ankylosing Spondylitis Using a Smart-Phone Management System: A Prospective Cohort Study.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic disease that decreases mobility, function, and quality of life. This study introduced the "Smart-phone SpondyloArthritis Management System" (SpAMS), an interactive mobile health (mHealth) tool designed for AS/spondyloarthritis (SpA) disease management and used SpAMS data to evaluate clinical characteristics of Chinese patients with AS. METHODS: SpAMS integrates patient's and physician's portals in a smart phone application. The Chinese Ankylosing Spondylitis Prospective Imaging Cohort was launched using SpAMS in April 2016. Patient self-assessments were completed online at baseline and at every subsequent clinic visit. Physician-reported assessments and treatments were recorded by rheumatologists during each visit. RESULTS: In total, 1201 patients with AS [mean (SD) age, 30.6 (8.7) years; male, 82.6%] were recruited. Mean (SD) disease duration was 8.4 (6.1) years. Past or current symptoms of acute anterior uveitis (AAU), psoriasis, and inflammatory bowel disease (IBD) were observed in 21.0%, 3.7%, and 9.4% of patients, respectively. AAU and IBD occurred significantly more in patients with symptom duration > 10 years. The most commonly used medications at baseline were nonsteroidal anti-inflammatory drugs (98.2%). Patients using tumour necrosis factor inhibitors accounted for 20.8%, and 66.4% of patients used conventional synthetic disease-modifying antirheumatic drugs. At baseline, 57.2% of patients had inactive disease (ID)/low disease activity (LDA); this rate significantly improved to 79.2% after a mean follow-up of 13.3 (5.9) months. Compared with relapsed patients, new achievers of ID/LDA underwent more online patient assessments (P < .001). Problems solved in SpAMS caused 29.1% of clinic visits to a tertiary hospital unnecessary. SpAMS saved an average of 5.3 hours and 327.4 RMB per person on traffic expenses; these expenses equalled 16% of the Chinese monthly disposable personal income. CONCLUSIONS: SpAMS is a time- and cost-saving disease management tool that can help patients with AS perform self-management and provide valuable data to clinicians.

Effectiveness of Subcutaneous Tumor Necrosis Factor Inhibitors in Patients With Ankylosing Spondylitis: A Real-World Prospective Observational Cohort Study in China.

Objective: This prospective observational study investigated the efficacy of tumor necrosis factor inhibitors (TNFis) on disease activity, physical functionality, and mobility in patients with ankylosing spondylitis (AS) in a real-world setting. Methods: The Chinese Ankylosing Spondylitis Prospective Imaging Cohort (CASPIC) is an ongoing cohort study. Patients with AS were included to one of two groups: the TNFi user group included those who received TNFi at any time point; the non-TNFi user group included those who did not receive TNFi. Disease activity, physical functionality, and mobility were assessed by AS Disease Activity Scores (ASDAS), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI), respectively. Results: A total of 804 patients with AS (241 TNFi users and 563 non-TNFi users) were recruited. For TNFi users, 83% received an etanercept biosimilar and 17.0% received adalimumab. Seventy-three TNFi users (30.3%) discontinued TNFis during the follow-up period; the mean duration of TNFi treatment was 6.9 ± 3.2 months. Reductions in ASDAS were significantly greater in TNFi users than in nonusers at 3, 6, and 12 months (differences in ASDAS reduction were 0.61, 0.56, and 0.46 units, respectively, all P < 0.05). Similarly, the improvement in BASFI was significantly greater in users than in nonusers at 3, 6, and 12 months (differences in BASFI improvement: 0.31, 0.75, and 0.74 units, respectively, all P < 0.05). BASMI increased in nonusers at 6 and 12 months (0.27, P = 0.47; 0.66, P < 0.001, respectively), but did not change in users (-0.16 and -0.13, respectively, both P > 0.05). At 12 months, changes in BASMI were significantly greater in nonusers than in users (-0.60, P = 0.47). Conclusion: TNFis are effective against disease activity and improve the physical functionality of patients with AS, even in those who taper or discontinue TNFis. Thus, TNFis may retard the progression of spinal mobility dysfunction in AS patients. TNF may maintain spinal mobility as indicated by the BASMI.