Janus kinase inhibitors for treating active ankylosing spondylitis: a meta-analysis of randomized controlled trials.

OBJECTIVE: In this study, we aimed to assess the safety and efficacy of Janus kinase (JAK) inhibitors in patients with ankylosing spondylitis (AS). METHODS: We conducted a Bayesian network meta-analysis using direct and indirect data from randomized controlled trials (RCTs), and examined the safety and efficacy of JAK inhibitors in active AS patients exhibiting inadequate response or intolerance to two or more non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: RCTs included a total of 406 patients (203 experimental subjects and 203 controls) from three studies on upadacitinib, filgotinib, and tofacitinib. Assessment of SpondyloArthritis International Society 20% improvement (ASAS20), ASAS40, and ASAS5/6 responses were significantly higher in the JAK inhibitor group than in the placebo group. Other efficacy outcomes, such as ASAS partial remission, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), Ankylosing Spondylitis Disease Activity Score (ASDAS), Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) scores, and Bath Ankylosing Spondylitis Functional Index (BASFI) were also significantly higher in the JAK inhibitor group compared to the placebo group. The JAK inhibitors significantly improved disease activity (ASAS partial remission, BASDAI50, ASDAS), function (BASFI), and MRI outcomes (SPARCC MRI spine). However, the incidence of adverse events (AEs) and serious adverse events (SAEs), and the rate of withdrawal attributed to AEs did not differ between the JAK inhibitor and placebo groups. CONCLUSION: JAK inhibitors were effective in active AS patients exhibiting an inadequate response or intolerance to two or more NSAIDs, without the risk of SAEs; this suggests that based on our data, studies are warranted to further investigate the use of JAK inhibitors for treating AS.

Anifrolumab for the treatment of active systemic lupus erythematosus: a meta-analysis of randomized controlled trials.

We surveyed randomized controlled trials (RCTs) examining the efficacy and safety of anifrolumab 300 mg in patients with active systemic lupus erythematosus (SLE) despite receiving standard therapy, using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis performed to determine treatment efficacy and safety outcomes of three RCTs (459 patients and 468 controls) revealed that the BICLA responses were significantly higher in the anifrolumab group than in the placebo group (OR = 2.071, 95%CI 1.575-2.725, p < 0.001). Steroid reduction and CLASI reduction were also significantly higher in the anifrolumab group than in the placebo group (OR = 1.811, 95%CI = 1.308-2.506, p < 0.001; OR = 2.245, 95%CI = 1.437-3.506, p < 0.001). Compared with placebo, anifrolumab significantly increased the SRI7 and SRI8 responses in SLE patients (OR = 1.866, 95%CI = 1.372-2.536, p < 0.001; OR = 1.925, 95%CI = 1.387-2.672, p < 0.001). The SRI4, 5, and 6 responses also tended to be higher in the anifrolumab group than in the placebo group. Adverse event incidence was significantly higher in the anifrolumab group than in the placebo group (OR = 1.815, 95%CI = 1.262-2.611, p = 0.001); serious adverse events were significantly lower in the anifrolumab group than in the placebo group (OR = 0.679, 95%CI = 0.468-0.986, p = 0.042). Herpes zoster infection was significantly higher in the anifrolumab group than in the placebo group (OR = 4.089, 95%CI = 1.750-9.522, p = 0.001). Anifrolumab is effective for treating active SLE. However, anifrolumab increased the incidence of herpes zoster infection compared with placebo.

Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in active rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs.

OBJECTIVE: The relative efficacy and tolerability of tofacitinib, baricitinib, upadacitinib, and filgotinib were assessed in patients with rheumatoid arthritis (RA) with inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, and filgotinib in RA patients with inadequate responses to bDMARDs. RESULTS: Four RCTs comprising 1399 patients met the inclusion criteria. Tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significant American College of Rheumatology 20% (ACR20) responses versus placebo. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by filgotinib 200 mg, baricitinib 4 mg, filgotinib 100 mg, tofacitinib 5 mg, and placebo. The ranking in SUCRA based on the ACR50 response rate indicated that baricitinib 4 mg had the highest probability of achieving the ACR50 response rate, followed by filgotinib 200 mg, tofacitinib 5 mg, upadacitinib 15 mg, filgotinib 100 mg, and placebo. Tofacitinib 5 mg showed a significantly higher ACR70 response rate than filgotinib 100 mg and upadacitinib 15 mg. Tofacitinib 5 mg, filgotinib 200 mg, and placebo showed a significantly lower serious adverse event rate than upadacitinib 15 mg. CONCLUSION: Tofacitinib, baricitinib, upadacitinib, and filgotinib were effective treatment options for RA patients with an inadequate response to bDMARDs but with different efficacy and safety profiles.

Circulating interleukin-23 levels in ankylosing spondylitis and their correlation with disease activity : A meta-analysis.

OBJECTIVE: To systematically investigate the relationship between circulating interleukin-23 (IL­23) levels and ankylosing spondylitis (AS) and establish a correlation between these hematological indices and AS activity/severity. METHODS: We searched the Medline, Embase, and Cochrane databases; performed a meta-analysis comparing serum/plasma IL­23 levels in patients with AS to those of controls; and examined the correlation coefficients between serum/plasma IL­23 levels and AS activity. RESULTS: Ten studies including 1724 patients with AS and 1589 controls were included in this meta-analysis. This meta-analysis showed that circulating IL­23 levels were significantly higher in the AS than in the control group (standardized mean difference [SMD] 1.479; 95% confidence interval [CI] 0.308-2.650; p = 0.013). Stratification by ethnicity showed a significantly increased IL­23 level in the AS group in an Asian population (SMD 1.551; 95% CI 0.543-2.558; p = 0.003). Stratification by adjustment for age and sex revealed significantly higher IL­23 levels in the AS adjustment group. Subgroup analysis of sample size showed a significantly higher IL­23 level for a small (n < 150) sample number in the AS group. Meta-analysis of correlation coefficients revealed that the IL­23 level was positively associated with the Bath Ankylosing Spondylitis Metrology Index (BASMI; correlation coefficient 0.464; 95% CI 0.027-0.752; p = 0.038), erythrocyte sedimentation rate (ESR; correlation coefficient 0.258; 95% CI 0.076-0.422; p = 0.006), and C­reactive protein (CRP; correlation coefficient 0.291; 95% CI 0.053-0.498; p = 0.017). CONCLUSION: This meta-analysis demonstrated that the circulating IL­23 level is significantly higher in patients with AS, and a significant positive correlation exists between the circulating IL­23 level and BASMI, ESR, and CRP.

Comparative efficacy and safety of mycophenolate mofetil versus cyclophosphamide in patients with active antineutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of randomized trials.

OBJECTIVE: This study aimed to assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC) in patients with active antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: We performed a meta-analysis of four randomized clinical trials (RCTs; 300 patients) to examine the relative efficacy and safety of MMF compared to CYC in patients with active AAV. RESULTS: There was no significant difference in remission at 6 months between MMF and CYC (odds ratio [OR] 1.311, 95% confidence interval [CI] 0.570-3.017, P = 0.524). Additionally, the relapse rate did not differ between the MMF and CYC groups (OR 1.331, 95% CI 0.497-3.568, P = 0.570). There was no significant difference in serious adverse event (SAE; OR 1.232, 95% CI 0.754-2.014, P = 0.404) and infection rates (OR 0.958, 95% CI 0.561-1.634, P = 0.873) between the MMF and CYC groups. Some heterogeneity was found in the meta-analysis of remission and relapse rates (I2 = 57.4%, 63.4%), but no between-study heterogeneity was found during the meta-analysis of SAE and infection rate. Egger's regression test showed no evidence of publication bias (Egger's regression test P-values >0.1). CONCLUSION: MMF was an equally effective alternative treatment to CYC and MMF was comparable to CYC in patients with active AAV in terms of safety, suggesting that MMF can be used as an alternative to CYC for remission induction in AAV.

Comparative efficacy and safety of secukinumab and ixekizumab in patients with active ankylosing spondylitis.

OBJECTIVE: Evaluation of the effectiveness and safety of secukinumab and ixekizumab in active ankylosing spondylitis (AS) patients. METHODS: A Bayesian network meta-analysis was conducted using direct and indirect data from five randomized controlled trials that examined the efficacy and safety of secukinumab 150 mg every 4 weeks and ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) in active AS patients. RESULTS: Data from 1433 patients were analyzed. The Assessment of Spondyloarthritis International Society evaluation 20% response rates (ASAS20) were significantly higher with secukinumab 150 mg, IXEQ2W, IXEQ2W, and adalimumab 40 mg (odds ratio [OR] 2.75, 95% Bayesian credible interval [CrI] 2.04-3.69; OR 2.59, 95% CrI 1.69-3.98; OR 2.45, 95% CrI 1.60-3.75; and OR 1.94, 95% CrI 1.13-3.37, respectively) compared to the placebo group. Efficacies of secukinumab and ixekizumab were numerically higher compared to adalimumab 40 mg, although there was no significant difference in the ASAS20 response rates. The ASAS40 response rate showed a pattern of distribution similar to the ASAS20 response rate, with the exception of the ixekizumab group, which was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ASAS40 response rate. Based on the SUCRA rating, secukinumab 150 mg had the highest probability of being the best ASAS20 response rate therapy, followed by IXEQ2W, IXEQ4W, adalimumab 40 mg, and placebo. There was no significant difference between the treatments regarding the number of serious adverse events (SAEs). CONCLUSION: Secukinumab and ixekizumab were effective in active AS treatment, without the risk of SAEs.

Comparative efficacy and safety of 15 and 30 mg upadacitinib administered to patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVES: We assessed the relative efficacy and safety of once-daily administration of 15 and 30 mg upadacitinib (a JAK1-selective inhibitor) in patients with active rheumatoid arthritis (RA). METHODS: We conducted a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) that examined the efficacy and safety of upadacitinib in patients with active RA. RESULTS: Five RCTs involving 4381 patients met the inclusion criteria. There were 15 pairwise comparisons, including eight direct comparisons and six interventions. The ACR20 response rate was significantly higher in the upadacitinib 15 and 30 mg + MTX (methotrexate) groups than in the MTX group (OR: 4.98, 95% CrI: 2.66-10.10; OR: 4.73, 95% CrI: 2.25-10.98). Adalimumab 40 mg + MTX, upadacitinib 30 mg, and upadacitinib 15 mg groups showed a significantly higher ACR20 response rate than did the MTX group. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that upadacitinib 15 mg + MTX was likely to achieve the best ACR20 response rate (SUCRA = 0.838), followed by upadacitinib 30 mg + MTX, adalimumab 40 mg + MTX, upadacitinib 30 mg, upadacitinib 15 mg, and MTX (SUCRA = 0.784, 0.495, 0.471, 0.404, and 0.008, respectively). The safety based on the number of serious adverse events (SAEs) did not differ significantly among the six interventions. CONCLUSIONS: Upadacitinib 15 and 30 mg administration once daily in combination with MTX was the most efficacious intervention for active RA, with no significant risk for SAEs.

Comparison of the efficacy and safety of tofacitinib and filgotinib in patients with active rheumatoid arthritis: a Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: We compared the efficacy and safety of tofacitinib and filgotinib in patients with rheumatoid arthritis (RA) showing inadequate response to conventional synthetic (cs) or biologic (b) disease-modifying anti-rheumatic drugs (DMARDs). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tofacitinib and filgotinib in combination with methotrexate (MTX) in patients with RA exhibiting inadequate cs- or bDMARD response. RESULTS: Nine RCTs consisting of 5466 patients met the inclusion criteria. We obtained 15 pairwise comparisons, including 11 direct comparisons from 6 interventions. Tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX were among the most effective treatments for active RA showing an inadequate cs- or bDMARD response, followed by tofacitinib 5 mg + MTX, filgotinib 100 mg + MTX, and adalimumab + MTX. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX showed the highest probability of being the best treatment options in terms of ACR20 response rate (SUCRA = 0.898, 0.782), followed by tofacitinib 5 mg + MTX (SUCRA = 0.602), filgotinib 100 mg + MTX (SUCRA = 0.359), adalimumab + MTX (SUCRA = 0.358), and placebo + MTX (SUCRA = 0.001). No significant differences were observed in the incidence of serious adverse events after treatment with tofacitinib + MTX, filgotinib + MTX, adalimumab + MTX, or placebo + MTX. CONCLUSION: In patients with RA exhibiting an inadequate response to cs- or bDMARDs, tofacitinib 10 mg + MTX and filgotinib 200 mg + MTX were the most efficacious interventions and risks of serious adverse events did not differ between tofacitinib and filgotinib groups.

Association between IL-17 gene polymorphisms and circulating IL-17 levels in osteoarthritis: a meta-analysis.

OBJECTIVE: This study systemically reviewed the evidence regarding associations between polymorphisms in interleukin-17 (IL-17) genes and osteoarthritis (OA) susceptibility, and the relationship between circulating IL-17 levels and OA. METHODS: We performed a meta-analysis of the associations between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk for OA and serum/plasma IL-17 levels in OA patients and controls. RESULTS: Eight studies including 2214 OA patients and 2474 controls were included. Our meta-analysis identified a significant association between OA and the AA genotype of the IL-17A rs2275913 polymorphism in a pooled cohort of affected individuals, compared to the case in a pooled cohort of control participants (OR = 1.516, 95% CI = 1.260-1.825, P < 0.001), and a significant association between OA and the CC genotype of the IL-17F rs763780 polymorphism (OR = 2.257, 95% CI = 1.376-3.704, p = 0.001). OA site-based stratification identified an association between the AA genotype of the IL-17A rs2275913 polymorphism and the CC genotype of the IL-17F rs763780 polymorphism and knee OA, but not hip OA. Furthermore, the same patterns of significant associations between OA and the IL-17A rs2275913 and IL-17F rs763780 polymorphisms were identified based on homozygote contrasts. The OA patients showed significantly higher IL-17 levels than the control subjects (SMD = 1.830, 95% CI = 1.184-2.477, P < 0.001). CONCLUSION: Our meta-analysis revealed associations between the IL-17A rs2275913 and IL-17F rs763780 polymorphisms and OA susceptibility, and the presence of significantly higher circulating IL-17 levels in OA patients.

Associations between interleukin-23R polymorphisms and ankylosing spondylitis susceptibility: an updated meta-analysis.

OBJECTIVE: The aim of this study was to determine whether interleukin-23R (IL-23R) polymorphisms are associated with susceptibility to ankylosing spondylitis (AS). METHODS: Meta-analyses were conducted to determine the associations between IL-23R polymorphisms and AS susceptibility in Europeans, Asians, and all subjects combined. RESULTS: A total of 17 studies (21 separate comparisons) were included in this meta-analysis. The meta-analysis revealed a significant association between AS and the two alleles of the rs11209032 polymorphism in all study subjects (odds ratio [OR] = 1.160, 95% confidence interval [CI] = 1.091-1.204, P < 0.001). Stratification by ethnicity identified a significant association between this polymorphism and AS in Europeans (OR = 1.234, 95% CI = 1.159-1.313, P < 0.001), but not in Asians (OR = 1.003, 95% CI = 0.920-1.219, P = 0.942). Meta-analyses of the rs1004819, rs10489629, rs1343151, rs1495965, rs7517847, and rs11465804 polymorphisms showed the same pattern as shown for rs11209032. The meta-analysis also revealed a significant association between the two alleles of the rs2201841 and rs11209026 polymorphisms and the risk of developing AS in Europeans, but not in Asians. Interestingly, the rs10889677 polymorphism was not found to be associated with AS susceptibility in either Europeans or Asians. CONCLUSIONS: This meta-analysis showed that several IL-23R polymorphisms are associated with the development of AS in Europeans.

Overall and cause-specific mortality in giant cell arteritis : A meta-analysis.

OBJECTIVE: This study aimed to assess the all-cause and cause-specific standardized mortality ratios (SMRs) in patients with giant cell arteritis (GCA). METHODS: We surveyed studies examining all-cause and/or cause-specific SMRs in patients with GCA compared to the general population, using MEDLINE, EMBASE, Cochrane databases, and manual searches. We then performed a meta-analysis of all-cause, sex-specific, region-specific, and cause-specific SMRs in patients with GCA. RESULTS: In total, 8 reports including 1972 patients with GCA (including 877 patients who died) met the inclusion criteria. Compared with the general population, all-cause SMR was not increased in patients with GCA (SMR 1.081, 95% confidence interval [CI] 0.963-1.214, p = 0.184). Stratification by region showed no significant increase in all-cause SMR in Europe and USA. Sex-specific meta-analysis revealed that the pooled SMR was 1.046 (95%CI 0.834-1.314, p = 0.696) for women and 1.051 (95%CI 0.974-1.133, p = 0.204) for men. There were no sex-specific significant differences in SMR. The risk of mortality due to cardiovascular disease (CVD) was significantly increased (SMR 1.312, 95%CI 1.136-1.516, p < 0.001). However, there was no significant increase in the SMR for mortality due to cancer (SMR 0.833, 95%CI 0.613-1.132, p = 0.243). CONCLUSIONS: Patients with GCA do not show increased rates of death from all causes, regardless of sex, region, or malignancy. However, these patients are at an increased risk of death due to CVD.

Association between circulating 25-hydroxyvitamin D levels and psoriasis, and correlation with disease severity: a meta-analysis.

BACKGROUND: Psoriasis is a chronic, autoimmune, inflammatory skin disorder. 25-hydroxy vitamin D [25(OH)D] deficiency may contribute to the pathogenesis of psoriasis through reduction in antiproliferative, anti-inflammatory and antiangiogenic activities. AIM: To evaluate the relationship between circulating 25(OH)D levels and psoriasis, and to determine the correlation between serum/plasma 25(OH)D levels and psoriasis severity. METHODS: We performed a meta-analysis to compare serum/plasma 25(OH)D levels between patients with psoriasis and healthy controls (HCs), and to determine the correlation coefficients between circulating 25(OH)D levels and psoriasis severity as assessed by Psoriasis Area and Severity Index (PASI). RESULTS: Ten articles with a total of 571 patients with psoriasis and 496 HCs were included. The 25(OH)D level was significantly lower in the psoriasis group than in the HC group. Subgroup analysis by sample size revealed a significantly lower level of 25(OH)D in the psoriasis group for large (N > 80) but not for small (N < 80) sample sizes. Stratification by adjustment for age and/or sex or sample type revealed a significantly lower 25(OH)D level in the psoriasis group after adjustment for serum but not after nonadjustment for plasma. Meta-analysis of the correlation coefficients revealed a small but statistically significant positive correlation between circulating 25(OH)D levels and PASI. CONCLUSIONS: This meta-analysis demonstrated that circulating 25(OH)D levels are lower in patients with psoriasis, and that a small but statistically significant negative correlation exists between 25(OH)D levels and psoriasis severity.

Association of circulating resistin, leptin, adiponectin and visfatin levels with Behçet disease: a meta-analysis.

BACKGROUND: Behçet disease (BD) is a chronic inflammatory disease. Adipokines are synthesized in adipose tissue, and have been reported to play important roles in the pathogenesis of autoimmune and inflammatory diseases, including BD. AIM: To evaluate the relationship between circulating blood adipokine levels and BD. METHODS: We conducted a meta-analysis of papers reporting on serum/plasma resistin, leptin, adiponectin and visfatin levels in patients with BD and in healthy controls (HCs). We identified 82 relevant studies using electronic and manual search methods, and selected 16 studies for full-text review based on the title and abstract. Two of these were later excluded (one was a review, one had no data), leaving 14 articles that met the inclusion criteria for this meta-analysis. RESULTS: The 14 included studies assessed 637 patients with BD and 520 HCs. Compared with the HCs, the BD group had significantly higher levels of leptin [standardized mean difference (SMD) = 0.68, 95% CI 0.15-1.21, P = 0.01]. Levels of resistin (SMD = 0.51, 95% CI 0.92-0.918, P = 0.02) and adiponectin (SMD = 0.31, 95% CI 0.06-0.56, P = 0.02) were significantly higher in the BD group after adjustment for age, sex and body mass index (BMI), but not without such adjustment (resistin: (SMD = 0.38, 95% CI -0.18 to 0.93, P = 0.19; adiponectin: SMD = -0.59, 95% CI -2.23 to 1.06, P = 0.48). A significantly lower visfatin level was found in the BD group with adjustment (SMD = -1.70, 95% CI -2.14 to -1.25, P < 0.001) but not without adjustment (SMD = 0.31, 95% CI -0.21 to 0.82, P = 0.24). CONCLUSIONS: Our meta-analysis revealed significantly higher circulating resistin, leptin and adiponectin levels and lower visfatin levels in patients with BD than in HCs, indicating that adipokines probably play an important role in BD pathogenesis.

Association between circulating prolactin levels and psoriasis and its correlation with disease severity: a meta-analysis.

BACKGROUND: Studies that have compared circulating prolactin (PRL) levels in patients with psoriasis and healthy controls (HCs) and determined the relation between PRL levels and psoriasis severity have shown mixed results. AIM: To evaluate the association between circulating PRL levels and psoriasis, and between serum/plasma PRL levels and psoriasis severity. METHODS: We performed a meta-analysis comparing serum/plasma PRL levels in patients with psoriasis with those of HCs, and examined the correlation coefficients for circulating PRL levels and psoriasis severity based on Psoriasis Area and Severity Index (PASI). RESULTS: In total, 12 studies assessing 446 patients with psoriasis and 401 HCs were included. PRL levels were significantly higher in the psoriasis group than in the HC group [standardized mean difference (SMD) 0.54; 95% CI = 0.18-090; P < 0.01). Stratification by age and sex revealed a significantly higher PRL level in the psoriasis group (SMD = 0.53; 95% CI = 0.15-0.91; P < 0.01). Subgroup analysis by sample size showed a significantly higher PRL level with larger sample sizes (n ≥ 80) (SMD = 0.51, 95% CI = 0.07-0.95, P = 0.02), but not with smaller sample sizes (n < 80) in the psoriasis group. Stratification by sample type revealed a significantly higher level of PRL in the sera, but not plasma of the psoriasis group. Meta-analysis of the correlation coefficients showed a positive, although not statistically significant, correlation between circulating PRL levels and PASI (correlation coefficient = 0.48, 95% CI = -0.05 to 0.80, P = 0.08). CONCLUSION: Circulating PRL levels are higher in patients with psoriasis, and PRL levels may correlate with psoriasis severity.

Relative efficacy and safety of apremilast, secukinumab, and ustekinumab for the treatment of psoriatic arthritis.

OBJECTIVE: To assess the relative efficacy and safety of apremilast, secukinumab, and ustekinumab at different doses in patients with active psoriatic arthritis (PsA). METHOD: A Bayesian network meta-analysis was conducted, which included randomized controlled trials (RCTs) that examined the efficacy and safety of apremilast 20 mg, apremilast 30 mg, secukinumab 75 mg, secukinumab 150 mg, secukinumab 300 mg, ustekinumab 45 mg, and ustekinumab 90 mg compared with placebo. RESULTS: Of the RCTs 8 comprising 3289 patients met the inclusion criteria. The American College of Rheumatology (ACR) 20 response rate was significantly higher in the secukinumab 300 mg group than in the placebo group (odds ratio OR, 7.55; 95% confidence interval CI, 3.18-17.63). Secukinumab 150 mg, secukinumab 75 mg, ustekinumab 90 mg, apremilast 30 mg, apremilast 20 mg, and ustekinumab 45 mg were also more efficacious than placebo. There were no significant differences in the efficacy between the interventions. A dose-response relationship among the same drug groups was observed. The number of serious adverse events was not significantly different among the apremilast, secukinumab, ustekinumab, and placebo groups. CONCLUSION: All drug treatments were more efficacious than placebo; however, there were no significant differences in the efficacy and safety between the drugs at the different doses.

Association between circulating leptin levels and systemic lupus erythematosus: an updated meta-analysis.

Objective We aimed to evaluate the relationship between circulating leptin levels and systemic lupus erythematosus (SLE). Methods MEDLINE, EMBASE, and Cochrane library databases were searched. Meta-analyses were performed comparing serum/plasma leptin levels in patients with SLE and healthy controls, and on patients with SLE in subgroups based on ethnicity, sample size, data type, and matched variables (age, sex, and/or body mass index (BMI)). Results Eighteen studies including 1333 patients with SLE and 1048 controls were ultimately selected, which showed that leptin levels were significantly higher in the SLE group than in the control group (SMD = 0.611, 95% CI = 0.275-0.947, p < 0.001). When we excluded two outlier studies because of high heterogeneity, leptin levels were also significantly higher in the SLE group than in the control group (SMD = 0.619, 95% CI = 0.431-0.807, p < 0.001). Stratification by ethnicity showed significantly elevated leptin levels in the SLE group in European, Asian, Arab, Latin American, and mixed populations. Subgroup analysis by sample size showed significantly higher leptin levels in the SLE group by small ( n ≤ 100) and large sample numbers ( n > 100) (SMD = 0.780, 95% CI = 0.445-1.115, p < 0.001; SMD = 0.495, 95% CI = 0.275-0.715, p < 0.001). Stratification by data type revealed significantly higher leptin levels in the original data and imputed data groups. Subgroup analysis adjustment revealed significantly higher leptin levels in the SLE group, regardless of adjustment for variables. Conclusions Our meta-analysis demonstrated that leptin levels were significantly higher in patients with SLE, regardless of ethnicity, sample size, data type, and matched variables.

Comparative efficacy and safety of intravenous or subcutaneous belimumab in combination with standard therapy in patients with active systemic lupus erythematosus: a Bayesian network meta-analysis of randomized controlled trials.

Objective In this study, we aimed to assess the relative efficacy and safety of intravenous (IV) or subcutaneous (SC) belimumab compared with those of placebo in patients with active systemic lupus erythematosus (SLE). Methods We performed a Bayesian network meta-analysis to combine the direct and indirect evidence from randomized controlled trials (RCTs) examining the efficacy and safety of belimumab 1 mg/kg and 10 mg/kg IV administration, and belimumab 200 mg SC injection, and placebo in patients with active SLE despite having received standard therapy. Results Five RCTs (3460 patients) met the inclusion criteria. The SLE Responder Index (SRI) response rate at week 52 was significantly higher in the belimumab 10 mg/kg group than in the placebo group (OR 2.63, 95% CrI 2.14-3.23). Similarly, the SRI response rates were significantly higher in the belimumab 1 mg/kg, and belimumab 200 mg SC groups than in the placebo group (OR 2.42, 95% CrI 1.90-3.09; OR 1.71, 95% CrI 1.27-2.29). Ranking probability based on surface under the cumulative ranking curve (SUCRA) indicated that belimumab 10 mg/kg had the highest probability of being the best treatment for achieving the SRI response (SUCRA = 0.9174), followed by belimumab 1 mg/kg (SUCRA = 0.7338), belimumab 200 mg SC (SUCRA = 0.3487), and placebo (SUCRA = 0.0000). However, a sensitivity test by omitting one outlier study showing low SRI response rate compared with the other three studies (11% vs. 33%, 40%, 48%) showed that belimumab 200 mg SC and belimumab 10 mg/kg had the highest probability of being the best treatment for achieving the SRI response (SUCRA = 0.7903, SUCRA = 0.7456), followed by belimumab 1 mg/kg, and placebo. The number of serious adverse events (SAEs) did not differ significantly among the four treatment options. Conclusions Belimumab at 1 and 10 mg/kg IV and belimumab 200 mg SC in combination with standard therapy was an efficacious intervention for active SLE, and was not associated with a significant risk of SAEs.

Circulating prolactin level in systemic lupus erythematosus and its correlation with disease activity: a meta-analysis.

Objective This study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin levels and SLE activity. Methods We performed a meta-analysis comparing the plasma/serum prolactin levels in patients with SLE to controls, and examined correlation coefficients between circulating prolactin level and SLE disease activity. Results Twenty-five studies with a total of 1056 SLE patients and 426 controls were included. Prolactin levels were significantly higher overall in the SLE group than in the control group (standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 × 10-5). Stratification by ethnicity showed significantly elevated prolactin levels in the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95% CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD = 1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European population. Subgroup analysis by sample size showed significantly higher prolactin levels in the SLE group by small ( n < 30) and large sample numbers ( n > 30). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating prolactin level and SLE activity (correlation coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 × 10-9). Circulating prolactin levels were positively associated with SLE activity in European, Asian, and mixed populations (SMD = 0.532, 95% CI = 0.443-0.609 p < 1.0 × 10-8; SMD = 0.427, 95% CI = 0.240-0.583, p = 2.4 × 10-5; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 × 10-5, respectively). Conclusions Our meta-analysis demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactin levels and SLE activity.

Adalimumab-induced pulmonary sarcoidosis not progressing upon treatment with etanercept.

Tumor necrosis factor alpha (TNF-α) inhibitors effectively treat sarcoidosis, but can, paradoxically, induce sarcoidosis. The TNF-α inhibitor etanercept is most commonly associated with paradoxical sarcoidosis, which has previously been reported to be resolved by adalimumab. However, we describe the case of a patient with ankylosing spondylitis and adalimumab-induced sarcoidosis not aggravated by switching to etanercept, thus indicating that etanercept could be a treatment option for patients who develop paradoxical sarcoid-like reactions after treatment with other TNF-α inhibitors.

Associations between SLC2A9 polymorphisms and gout susceptibility : A meta-analysis.

OBJECTIVE: The aim of this study was to determine whether polymorphisms in solute carrier family 2 and facilitated glucose transporter member 9 (SLC2A9) are associated with susceptibility to gout. METHODS: A meta-analysis was conducted on associations between the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 and gout susceptibility using fixed and random effects models. RESULTS: Eleven comparative studies comprising 1,472 patients and 3,269 controls from Caucasian and Asian populations were included in this meta-analysis. The meta-analysis identified a significant negative association between gout and allele 2 (minor) of the rs12510549 polymorphism in the overall population (OR = 0.641, 95 % CI = 0.540-0.761, P = 4.1 × 10-7). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.647, 95 % CI = 0.542-0.771, P = 1.2 × 10-6) but not in Asians (OR = 0.515, 95 % CI = 0.214-1.236, P = 0.137). The meta-analysis showed a significant negative association between gout and allele 2 of the rs16890979 polymorphism in all study subjects (OR = 0.229, 95 % CI = 0.084-0.628, P = 0.004). Stratification by ethnicity identified a significant negative association between this polymorphism and gout in Caucasians (OR = 0.469, 95 % CI = 0.317-0.695, P = 1.6 × 10-6) and in Asians (OR = 0.192, 95 % CI = 0.072-0.513, P = 0.001). A significant negative association was found between allele 2 of the rs1014290 polymorphism and gout susceptibility in Asians (OR = 0.597, 95 % CI = 0.478-0.746, P = 5.4 × 10-6) but not in Caucasians (OR = 0.778, 95 % CI = 0.595-1.043, P = 0.095). CONCLUSIONS: This meta-analysis shows that the rs12510549, rs16890979, and rs1014290 polymorphisms of SLC2A9 protect against the development of gout in Caucasians and/or Asians.