Cyclophosphamide in the Treatment of Systemic Lupus Erythematosus-related Guillain-Barré Syndrome: A Systematic Review of Case Reports.

A small category of Guillain-Barré syndrome (GBS) occurs in the presence of systemic lupus erythematosus (SLE). However, specific treatments for this condition have not been established. Cyclophosphamide (CYC) has been reported to benefit patients with SLE-related GBS in some isolated case reports. Consequently, our objective was to investigate the effectiveness of CYC in SLE-related GBS by means of a systematic literature review. Three online databases, PubMed, Embase and Web of Science, were searched for English articles describing the effectiveness of CYC treatment for SLE-related GBS. We extracted data on patient characteristics, disease course, and CYC efficacy and tolerance. Of 995 studies identified, 26 were included in this systematic review. The data for 28 patients (9 men and 19 women) with SLE-related GBS were reviewed, and the patient age at diagnosis varied from 9 to 72 years (mean: 31.5 years [median: 30.5 years]). Sixteen patients (57.1%) had SLE-related GBS before SLE diagnosis. With regard to CYC response, 24 patients (85.7%) showed resolution (46.4%) or improvement (39.3%) of neurological symptoms. Relapse occurred in one patient (3.6%). Four patients (14.3%) showed no improvement in neurological symptoms following CYC administration. With regard to CYC safety, infections developed in two patients (7.1%), and one death (3.6%) due to posterior reversible encephalopathy syndrome was reported. Lymphopenia developed in one patient (3.6%). Our preliminary data suggest that CYC appears to be an effective treatment for SLE-related GBS. However, it is important to differentiate patients with pure GBS concurrent with SLE, because CYC is ineffective for pure GBS.

The therapeutic efficacy and safety of intravenous immunoglobulin in dermatomyositis and polymyositis: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and safety of intravenous immunoglobulin (IVIG) in the treatment of dermatomyositis (DM) and polymyositis (PM). METHODS: We searched PubMed, Embase, and the China National Knowledge Infrastructure for relevant studies from July 1919 to May 2021. RESULTS: Seventeen papers pertinent to our questions were found: In a meta-analysis, we found that IVIG significantly improved the level of CK (SMD (STD. Mean Difference) = -0.69; 95%CI -0.93, -0.46; P < 0.0001), Manual Muscle Test (SMD = 1.12; 95%CI 0.77, 1.47; P < 0.00001), Medical Research Council (SMD = 1.59; 95%CI 0.86, 2.33; P < 0.00001), Activities of Daily Living (SMD = 1.07; 95%CI 0.59, 1.56; P < 0.0001). The CK levels in DM and PM were also significantly improved after IVIG (SMD = -0.73; 95%CI -1.12, -0.34; P = 0.0002 and SMD = -3.29; 95%CI -5.82, -0.76; P < 0.0001, respectively). The meta-analysis of three RCTs showed that there was a statistically significant improvement after IVIG (SMD = 0.63; 95%CI 0.22, 1.03; P = 0.002). In a random effects model, pooled muscle power improvement rate was 77% (95% CI: 66.0-87.0%). Meta-analyses of IVIG as first-line therapy showed a significant improvement of the CK level (SMD = -0.71; 95%CI -1.12, -0.30; P = 0.0007). The polled improvement rate of oesophageal disorders was 88% (95% CI: 80.0-95.0%). There was no statistically significant difference in the rate of improvement between the number of courses <2 and ≥2 (0.80% vs. 0.80%, P = 0.9). The proportion of corticosteroid-sparing success reached 81.8%. Adverse reactions following IVIG administration are usually mild and transient. Seven patients developed serious adverse events. CONCLUSION: IVIG seems to be an effective drug for DM/PM, improving muscle strength, CK levels, and oesophageal involvement, and it is well tolerated by patients.

Cyclophosphamide for Treatment of Refractory Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Systematic Review and Meta-analysis.

PURPOSE: This study evaluates the tolerability and efficacy of cyclophosphamide (CYC) for the treatment of refractory chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: We searched PubMed, Embase, Cochrane Library, and 2 Chinese databases (Chinese National Knowledge Infrastructure and SinoMed) for studies published between database inception and September 30, 2021. Articles obtained using the appropriate keywords were independently selected by 2 reviewers on the basis of the established inclusion and exclusion criteria. FINDINGS: In total, 240 records that were eventually curtailed to 13 studies with 83 patients were retrieved and subsequently included in this evaluation. All 13 studies were included in the systematic review, 7 of which were included in the meta-analysis. The pooled estimate of the response rate was 68% (95% CI, 45%-90%). The pooled estimate of the adverse reaction rate was 8% (95% CI, 0%-15%). The disease duration before the first CYC treatment was negatively correlated with the reduction in the modified Rankin Scale score (r = -0.76, P < 0.001). However, the response rates did not differ significantly between patients of different sexes (P = 0.716) or between patients who received and those who did not receive concurrent glucocorticoids (P = 0.617). IMPLICATIONS: CYC might be a recommended therapeutic option for patients with refractory CIDP, especially those who are unable to accept rituximab treatment. Earlier CYC treatment yields better therapeutic outcomes in patients with refractory CIDP without CYC-related contraindications.

Increased risk of mortality in systemic sclerosis-associated pulmonary hypertension: a systemic review and meta-analysis.

BACKGROUND: Pulmonary hypertension (PH) is a frequent complication of systemic sclerosis (SSc) and is currently one of the primary causes of death in patients with this disease. We conducted a systematic review and meta-analysis to assess the association between PH and mortality in patients with SSc to verify trends in mortality in patients with SSc-associated PH. METHODS: We searched the PubMed and Embase databases for published studies on SSc-associated PH from inception to May 2021. All cohort studies in which mortality and/or survival for SSc-associated PH were reported were included in the analysis. The outcome parameters were pooled and analyzed using a random-effects model via generic inverse-variance weighting in conventional and cumulative meta-analysis. RESULTS: The literature search identified 1161 citations, and the full texts of 54 studies were examined. Sixteen articles, with a total of 7857 patients with SSc and 1140 patients with SSc-associated PH, were included in the meta-analysis. Patients with SSc-associated PH had a higher pooled risk of mortality than patients with SSc without PH (risk ratio = 3.12; 95% confidence interval: [2.44, 3.98]). CONCLUSIONS: This meta-analysis revealed a higher mortality in patients with SSc-associated PH. PH was a significant predictor of death in patients with SSc. Thus, early diagnosis and treatment of PH are important in patients with SSc.

Angiotensin-converting enzyme inhibitors prior to scleroderma renal crisis in systemic sclerosis: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Angiotensin-converting enzyme inhibitors (ACEIs) are widely used in the treatment of scleroderma renal crisis (SRC), and their use prior to the onset of SRC in patients with systemic sclerosis (SSc) has received wide attention in recent years. We undertook an evidence-based approach to identify whether the use of ACEIs prior to the onset of SRC is beneficial for patients with SSc. METHODS: We searched PubMed and Embase for any published studies produced between database inception and 22 October 2021. Articles obtained after using appropriate keywords were selected independently by two reviewers according to the established inclusion and exclusion criteria. RESULTS: Nine studies were included. Pooled results indicated that using ACEIs prior to SRC was associated with a higher incidence of SRC than no ACEIs prior to SRC (RR 2.05, 95% confidence interval 1.08-3.91, p = 0.03). Compared with patients who did not use ACEIs prior to the onset of SRC, a higher proportion of patients with SRC who used ACEIs prior to its onset had a poorer prognosis (RR 1.46, 95% confidence interval 1.20-1.78, p < 0.01). The difference in mortality between patients who used ACEIs prior to SRC onset and those who did not was not statistically significant (RR 1.12, 95% confidence interval 0.76-1.65, p = 0.57). WHAT IS NEW AND CONCLUSIONS: We recommend against using ACEIs prior to SRC in SSc patients. The use of ACEIs prior to SRC is associated with a higher incidence of SRC and poorer prognosis, especially in patients with progressive SSc or SSc-related renal vasculopathy (SSc-related hypertension and proteinuria).

Cardiovascular events in adult polymyositis and dermatomyositis: a meta-analysis of observational studies.

OBJECTIVES: We aimed to review whether PM and DM patients have an increased cardiovascular (CV) risk, including ischaemic heart disease (IHD), cerebrovascular accidents (CVA) and venous thromboembolism. METHODS: We searched PubMed, Embase and the Cochrane database for relevant studies from inception to February 2021. RESULTS: Twenty-two studies comprising 25 433 patients were included. With PM/DM vs general populations, the risk was significantly increased for CV events [relative risk (RR) = 2.37, 95% CI: 1.86, 3.02]. The RR of CV events for males with PM/DM was higher than for females (RR = 1.43; 95% CI: 1.17, 1.74). PM/DM patients followed for one to five years had a significantly higher CV risk than those followed for five to ten years (RR = 3.51, 95% CI: 1.95, 6.32). The risk was increased for North Americans (RR = 4.28, 95% CI: 2.57, 7.11), Europeans (RR = 2.29, 95% CI: 1.58, 3.31) and Asians (RR = 2.03, 95% CI: 1.41, 2.90). Our meta-analysis found that the elevated CV event risk was related to PM (RR = 2.35, 95% CI: 1.51, 3.66) and DM (RR = 2.55, 95% CI: 1.66, 3.93). Subgroup analyses showed that the risk was significantly increased for IHD (RR = 1.76, 95% CI: 1.40, 2.21), CVA morbidity (RR = 1.31, 95% CI: 1.03, 1.67) and ischaemic stroke (IS) (RR = 1.47, 95% CI: 1.26, 1.73), with no statistically significant increased risk of haemorrhagic stroke mortality (RR = 1.43, 95% CI: 0.92, 2.21). The CV event risk was increased for venous thromboembolism (RR = 4.60, 95% CI: 3.17, 6.66), deep venous thrombosis (RR = 5.53, 95% CI: 3.25, 9.39) and pulmonary embolism (RR = 5.26, 95% CI: 2.62, 10.55). CONCLUSION: This meta-analysis found that PM/DM patients had a ∼2.37 times increased CV risk, particularly males diagnosed in the previous five years. PM/DM may be an independent risk factor for developing IHD, IS, deep venous thrombosis and pulmonary embolism.

Increased risk of mortality in systemic sclerosis-associated pulmonary hypertension: a systemic review and meta-analysis

Abstract Background: Pulmonary hypertension (PH) is a frequent complication of systemic sclerosis (SSc) and is currently one of the primary causes of death in patients with this disease. We conducted a systematic review and meta-analysis to assess the association between PH and mortality in patients with SSc to verify trends in mortality in patients with SSc-associated PH. Methods: We searched the PubMed and Embase databases for published studies on SSc-associated PH from inception to May 2021. All cohort studies in which mortality and/or survival for SSc-associated PH were reported were included in the analysis. The outcome parameters were pooled and analyzed using a random-effects model via generic inverse-variance weighting in conventional and cumulative meta-analysis. Results: The literature search identified 1161 citations, and the full texts of 54 studies were examined. Sixteen articles, with a total of 7857 patients with SSc and 1140 patients with SSc-associated PH, were included in the metaanalysis. Patients with SSc-associated PH had a higher pooled risk of mortality than patients with SSc without PH (risk ratio = 3.12; 95% confidence interval: [2.44, 3.98]). Conclusions: This meta-analysis revealed a higher mortality in patients with SSc-associated PH. PH was a significant predictor of death in patients with SSc. Thus, early diagnosis and treatment of PH are important in patients with SSc.