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BACKGROUND@#Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs).@*METHODS@#A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure.@*RESULTS@#In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003).@*CONCLUSION@#This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
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Humans , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Network Meta-Analysis , Pharmaceutical Preparations , Randomized Controlled Trials as Topic , Tuberculosis/drug therapyABSTRACT
Objective:To analyze bone strength index, osteoporosis and fracture in ankylosing spondylitis (AS) patients with radiologic hip involvement and explore the characteristics of bone strength in these patients.Methods:According to bath ankylosing spondylitis radiology hip index (BASRI-hip) score, 339 AS patients were divided into two groups. The differences of bone strength in each group were analyzed by t-test, Mann-Whitney U test and χ2 test. Logistic regression was used to analyze the risk factors of bone strength index. The correlation between quantitative ultrasound and dualenergy X-ray absorptiometry (DXA) (total hip, g/cm 2) was analyzed. Pearson correlation analysis was used. Results:①Bone strength index of quantitative ultrasound was positively correlated with bone mineral density of DXA (total hip, g/cm 2), r=0.553, P<0.01. ② The age of 27(23, 37) years old in radiographic hip involvement was lower than 37(28, 48) years old in non-radiographic hip involvement, and the difference was statistically significant ( Z=-5.986, P<0.01). There were no differences in gender and course of disease between the two groups ( P>0.05).③ The radiographic hip involvement in AS patients whose ages were younger than 50, when compared with non-radiographic hip involvement patients, the bone strength index was lower (78±18 vs 84±16), while bone strength was lower than patients at the same age (41.0% vs 18.4%), however, the incidences of osteoporosis (42.7% vs 28.8%) and fragility fracture (3.7% vs 0%) were significantly higher ( t=3.028, P<0.01; χ2=16.758, P<0.01; χ2=5.886, P=0.019; χ2=4.67, P=0.038). For AS patients whose ages were ≥50, there were no significant differences between the two groups ( P>0.05). ④ Multivariate analysis showed that radiographic hip involvement [ OR (95% CI)=1.912(1.05, 3.48)], age [ OR (95% CI)=0.94(0.911, 0.97)] and body mass index (BMI) (kg/m 2) [ OR (95% CI) =0.875(0.807, 0.948)] were associated with lower bone strength. Conclusion:There is positive correlation between the bone strength index of quantitative ultrasound and bone mineral density of DXA. AS patients with radiographic hip involvement are characterized by decreased bone strength and are more likely to develop osteoporosis and fragile fractures. The risk factors of low bone strength are radiographic hip involvement, age and BMI.
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Objective:To explore the clinical characteristics of juvenile-onset ankylosing spondylitis.Methods:Clinical data of 350 cases of ankylosing spondylitis diagnosed in Beijing Jishuitan Hospital from January 2014 to December 2019 were collected. There were 75 cases with the symptom onset in age ≤16 years (juvenile-onset ankylosing spondylitis, JoAS), and 275 cases with the symptom onset in age>16 years (adult-onset ankylosing spondylitis, AoAS). The clinical characteristics of two groups were analyzed.Results:Compared with AoAS, JoAS had a higher proportion of males [98.7% (74/75) vs. 79.6% (219/275); χ 2=15.65, P<0.01] and longer course of disease [11(8,15) vs. 8(4,15) years; Z=-3.09, P<0.01]. Compared with AoAS, JoAS was more prone to have peripheral joint swelling and pain [45.3%(34/75) vs. 18.9%(52/275), χ 2=22.20, P<0.01], hip pain [26.7%(20/75) vs. 15.3%(42/275), χ 2=5.25, P=0.03] or heel pain [9.3%(7/75) vs. 2.9%(8/275), χ 2=5.93, P=0.02] as the first clinical manifestation. Compared with AoAS, JoAS had a higher incidence of radiological hip involvement [77.3%(58/75) vs. 43.3%(119/275), OR=4.71, Wald=25.60, P<0.01], lower bone mineral density than peers [34.7%(26/75) vs. 23.3%(64/275), OR=2.23, Wald=7.20, P<0.01], higher incidence of malnutrition [25.3%(19/75) vs. 13.8%(38/275), OR=2.16, Wald=5.84, P=0.02] and higher incidence of acute uveitis [17.3%(13/75) vs. 6.5%(18/275), OR=2.72, Wald=6.24, P=0.01] after adjusting the course of disease. Conclusion:Compared with adult-onset ankylosing spondylitis, juvenile-onset ankylosing spondylitis is more prone to have peripheral joint swelling or hip pain as the first clinical manifestation; the radiological hip involvement, lower bone mineral density than peers, malnutrition and uveitis are more likely to occur.
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Objective In order to assess the structure damage of hip joint in ankylosing spondylitis (AS), a new radiograph-based scoring method was developed according to the radiological characteristics of hip involvement in AS, as well referring to prior existing scoring indexes. Methods A new scoring method consti-tuted of erosion, sclerosis and joint space narrowing was developed, pelvis anterior-posterior plain films acquired from patients with AS at baseline and follow-up were collected and assessed by two physicians who were trained in image reading by radiologists. All films were scored independently and blindly. Intra- and inter-reader reliability were assessed by intra-class correlation coefficient (ICC), the feasibility of this new scoring method was assessed by the mean time acquired to score a plain (two hips), its ability to detect the change of structure damage was assessed by the comparison of score differences between baseline and different follow-ups. The date were analyzed by paired-t test or nonparametric tests. Analysis of Variance (ANOVA) or nonparametric tests were utilized for the comparison of means of quantitative variables among the three groups, while Chi-square test for rates of categorical variables. Results No statistically significant differences existed in demographic data and suspected risk factors among the three groups at baseline (P>0.05). Intra-observer reliability was good (0.84 and 0.89), as well as the inter-observer reliability (0.72), the mean time needed to score was (33 ±10) seconds. Score changes were not statistically significant in the groups with follow-up duration of 1-2 and 3-4 years, but in the group of over 5 years, baseline/final scores assessed by the two observers were (6.0±2.7/7.5±3.7) and (5.6±2.1/7.1±3.6), respectively, both changes were statistically significant (t=2.86, Z=-2.99; P<0.01). Conclusion This new method is not only reproducible and easy to operate in clinic practice, but also can tell the changes of hip joint structure damage in the interval of over 5 years, further validation is requeired to demonstrate its discriminability in large populations.
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Objective To investigate the clinical characteristics of paraneoplastic syndrome with prominent osteoarticular involvement. Methods The clinical materials of 20 patients with paraneoplastic syndrome with prominent osteoarticular involvement were collected. The characteristics of clinical manifest-ations, laboratory tests and imagines were analyzed. Results Among the 20 patients, 16 were male and 4 were female, with a mean age of 44.5 years and a median course of 6 months. Ten cases were associated with hematological tumor and 10 cases were associated with solid tumor. Eleven cases presented as peripheral arthritis (7 cases of polyarthritis, 4 cases of oligoarthritis/monoarthritis), 5 cases presented with hypertrophic osteoarthropathy (HOA) and 4 cases presented with tumor-induced osteomalacia (TIO). Three cases were acute lymphocytic leukemia, 2 cases were multiple myeloma, 1 case was lymphoma, and 1 case was bone tumor in polyarthritis. Four oligoarthritis cases were all associated with acute lymphocytic leukemia. All 5 cases of HOA were associated with lung cancer. All 4 cases of TIO were associated with tumor of mesenchymal tissue. Extra-articular manifestations presented in 14 cases and inflammatory markers increased in 15 cases. anti-cyclic cirullinated peptide (anti-CCP) antibodies was low titer positive in only 1 case and other parameters including rheumatoid factor (RF), anti-CCP antibodies, antinuclear antibodies spectrum (ANAs) and human leukocyte antigen (HLA)-B27 were negative. Multiple bone imaging abnormalities appeared in 15 cases. Conclusion Osteoarticular manifestations may be the first symptom of malignancy and difficult to diagnose. It is necessary to be highly aware of potential malignancy.
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Objective To investigate the effect of CXCL16 on the development of murine collageninduced arthritis (CIA). Methods CXCL16 mRNA of the involved synovium and serum CXCL16 protein were determined respectively by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA) in murine collagen-induced arthritis. The proliferation of lymphocytes from murine spleen and the level of RANKL mRNA, stimulated by CXCL16 at different concentrations (0,100, 200, 400, 800 ng/ml), was detected respectively by CCK-8 and RT-PCR, then the level of IL-2 and IFN-γ in culture supernatant was detected by ELISA. Comparisons between groups were tested by t test and one-way ANOVA analysis. Results The serum CXCL16 [(127± 10) vs (72±8) pg/ml, P＜0.05] and synovial CXCL16 mRNA (0.214±0.007 vs 0.375±0.009, P＜0.01) in CIA were all significantly higher than those in normal controls. The proliferation of CXCL16 (200, 400, 800 ng/ml) in CIA mouse lymphocytes, was significantly higher than that of CXCL16 (0 ng/ml) (0.51±0.06, 0.56±0.05, 0.55±0.04, (0.41±0.04, P＜0.05). And CXCL16 on the CIA stimulated lymphocyte proliferation was significantly higher than controls on normal lymphocytes (P＜0.05). Compared with blank control group, the expression of IL-2, IFN-γ and RANKL mRNA of CIA CXCL16 (400, 800 ng/ml) groups was higher significantly (P＜0.01). Conclusion CXCL16 plays an important role in the development of murine CIA by activating lymphocytes.