Efficacy and safety of intravenous and subcutaneous immunoglobulin therapy in idiopathic inflammatory myopathy: A systematic review and meta-analysis

ObjectiveTo perform a systematic review and meta-analysis on the efficacy and safety of intravenous (IVIg) and subcutaneous (SCIg) immunoglobulin (Ig) therapy in the treatment of idiopathic inflammatory myopathy (IIM) and juvenile dermatomyositis (JDM).MethodsPubMed, Embase and SCOPUS were searched to identify studies on Ig therapy in patients with IIM and/or JDM (2010?2020). Outcome measures were complete response (CR) or partial response (PR) in terms of muscle power and extramuscular disease activity measures on the International Myositis Assessment and Clinical Studies Group (IMACS) core set domains.ResultsTwenty-nine studies were included (n = 576, 544 IIM, 32 JDM). Muscle power PR with pooled Ig therapy was 88.5% (95% confidence interval (CI): 80.6–93.5, n = 499) and PR with SCIg treatment was 96.61% (95% CI: 87.43–99.15, n = 59). Pooled PR with first-line use of IVIg was 77.07% (95% CI: 61.25–92.89, n = 80). Overall, mean time to response was 2.9 months (95% CI: 1.9–4.1). Relapse was seen in 22.76% (95% CI: 14.9–33). Studies on cutaneous disease activity and dysphagia showed significant treatment responses. Glucocorticoid and immunosuppressant sparing effect was seen in 40.9% (95% CI: 20–61.7) and 42.2% (95% CI: 20.4–64.1) respectively. Ig therapy was generally safe with low risk of infection (1.37%, 95% CI: 0.1–2.6).ConclusionsAdd-on Ig therapy improves muscle strength in patients with refractory IIM, but evidence on Ig therapy in new-onset disease and extramuscular disease activity is uncertain.     

Efficacy of intravenous immunoglobulin in autoimmune neurological diseases. Literature systematic review and meta-analysis

BackgroundCorticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement.ObjectiveTo compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis.MethodsA systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study.ResultsOur meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40–5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45–1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58–1.68, P = 0.13).ConclusionIVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.     

Efficacy and safety of abatacept in interstitial lung disease of rheumatoid arthritis: A systematic literature review

BackgroundInterstitial lung disease (ILD) is a serious complication that represents the second leading cause of death in patients with rheumatoid arthritis (RA). Treatment of RA-ILD remains controversial. The absence of randomized clinical trials and specific ACR or EULAR therapeutic guidelines makes it difficult to establish solid therapeutic recommendations on this issue. In this scenario, real-world data is especially valuable.ObjectiveTo review the literature evidence on the efficacy and safety of abatacept (ABA) for the treatment of rheumatoid arthritis (RA) with associated interstitial lung disease (ILD), given its clinical relevance and the lack of consensus on its therapeutic management.MethodsPUBMED and EMBASE were searched from the date of approval of ABA to the end of 2020 using a combination of RA, ILD and ABA terms following PRISMA guidelines. Identified studies were evaluated by two independent investigators.ResultsNine original studies (1 case series and 8 observational studies) were selected for inclusion in the systematic review. No randomized trial or meta-analysis were identified. The mean age of patients ranged from 61.2 to 75 years and the mean RA duration varied from 7.4 to 18 years. Subcutaneous ABA (74.5%–91%) predominated in combination with conventional synthetic DMARDs (csDMARDs) (58%–75%), and it was used as first-line biologic agent in 22.8%–64.9% of the patients. The mean course of ILD ranged from 1 to 6.7 years, being usual and nonspecific interstitial pneumonia the most frequent patterns. Improvement or stabilization of ILD imaging (76.6%–92.7%) and FVC or DLCO (>85%) was described after a mean follow-up of 17.4–47.8 months, regardless of the pattern of lung involvement, being more remarkable in patients with shorter evolution of ILD. ABA led to significantly lower ILD worsening rates than TNF inhibitors (TNFi) and was associated with a 90% reduction in the relative risk of deterioration of ILD at 24 months of follow-up compared to TNFi and csDMARDs. Combination with methotrexate may have a corticoid-sparing effect. No unexpected adverse events were identified.ConclusionsCurrent evidence suggests that ABA may be a plausible alternative to treat RA patients with ILD. It would be highly desirable to develop prospective randomized controlled studies to confirm these findings.     

Efficacy and safety of medical cannabinoids in older subjects: A systematic review

This systematic review aims to integrate the evidence on indications, efficacy, safety and pharmacokinetics of medical cannabinoids in older subjects. The literature search was conducted using PubMed, EMBASE, CINAHL and Cochrane Library. We selected controlled trials including solely older subjects (=65 years) or reporting data on older subgroups. 105 (74%) papers, on controlled intervention trials, reported the inclusion of older subjects. Five studies reported data on older persons separately. These were randomized controlled trials, including in total 267 participants (mean age 47–78 years). Interventions were oral tetrahydrocannabinol (THC) (n = 3) and oral THC combined with cannabidiol (n = 2). The studies showed no efficacy on dyskinesia, breathlessness and chemotherapy induced nausea and vomiting. Two studies showed that THC might be useful in treatment of anorexia and behavioral symptoms in dementia. Adverse events were more common during cannabinoid treatment compared to the control treatment, and were most frequently sedation like symptoms. Although trials studying medical cannabinoids included older subjects, there is a lack of evidence of its use specifically in older patients. Adequately powered trials are needed to assess the efficacy and safety of cannabinoids in older subjects, as the potential symptomatic benefit is especially attractive in this age group.     

Transverse myelitis in systemic lupus erythematosus: A case report and systematic literature review

ObjectiveAcute transverse myelitis (TM) is a rare complication secondary to systemic lupus erythematosus (SLE) that can cause patients' extensive and severe neuropsychiatric disorders. Due to the rarity of the onset of acute TM, there is still no standard treatment protocol. This study was to summarize the clinical features of SLE-TM through a case report and systematic review.MethodsWe report a case of acute TM with the initial symptoms of headache and fever on admission to hospital, with lesions in medulla oblongata, cervical medulla, and thoracic medulla. Furthermore, all cases of SLE combined with acute TM from January 1975 to February 2022 were concluded and reviewed to compare the disease's current treatment strategies and prognosis.ResultsPatients with SLE-TM are mainly female (97.65%), with an average age of 36.89, a TM incidence of 24.51% and a longitudinal myelitis (LM) incidence of 67.76%. In addition, 68.63% of patients present an increased albumin, and only 16.50% of patients could recover. 32.35% of patients showed positive anti-cardiolipin antibody. Moreover, the patients who could recover are generally younger than those in the improved and paraparesis groups. After classifying the statistical results twice according to magnetic resonance imaging results and prognosis respectively, the erythrocyte sedimentation rate (ESR) in LM group was significantly higher than that in the other two groups. The positive rate of anti-DNA and anti-cardiolipin antibody (ANCL) in TM group was significantly higher than that of the other groups. According to the prognostic grouping, ESR in the recovery group was significantly higher than those in the other two groups. The positive ANCL in the poor prognosis group was slightly higher than that in the other two groups.ConclusionWe offer a novel insight for this rare disease and hope to bring some inspiration the basic research for SLE-TM.     

Role of TWEAK in lupus nephritis: A bench-to-bedside review

There is significant unmet need in the treatment of lupus nephritis (LN) patients. In this review, we highlight the role of the TWEAK/Fn14 pathway in mediating key pathologic processes underlying LN involving both glomerular and tubular injury, and thus the potential for renal protection via blockade of this pathway. The specific pathological mechanisms of TWEAK - namely promoting inflammation, renal cell proliferation and apoptosis, vascular activation and fibrosis - are described, with supporting data from animal models and in?vitro systems. Furthermore, we detail the translational relevance of these mechanisms to clinical readouts in human LN. We present the opportunity for an anti-TWEAK therapeutic as a renal protective agent to improve efficacy relative to current standard of care treatments hopefully without increased safety risk, and highlight a phase II trial with BIIB023, an anti-TWEAK neutralizing antibody, designed to assess efficacy in LN patients. Taken together, targeting the TWEAK/Fn14 axis represents a potential new therapeutic paradigm for achieving renal protection in LN patients.     

Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis

ObjectivesCytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients.MethodsData sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I². We assessed the certainty of evidence using the GRADE approach.ResultsOf 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I² = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I² = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I² = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively.ConclusionsCumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.     

Efficacy and safety of echinocandin monotherapy and combination therapy for immunocompromised patients with systemic candidiasis: A systematic review and meta-analysis

BackgroundSystemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so.MethodsA protocol was prepared a priori. PubMed, Embase and Cochrane Library databases were searched systematically (from inception of each database to September 2022) to identify randomized controlled trials. Two reviewers performed screening, quality assessment of trials, and extracted data independently. Pairwise meta-analysis was performed using random-effects model to compare echinocandin monotherapy versus other antifungals. The primary outcomes of interest were treatment success and treatment-related adverse events.Results547 records (PubMed=310, EMBASE=210 and Cochrane Library=27) were reviewed. Following our screening criteria, six trials involving 177 patients were included. Risk of bias of four included studies had some concerns due to lack of a pre-specified analysis plan. Meta-analysis shows that echinocandin monotherapy does not have significantly higher rates of “treatment success” compared to other classes of antifungals (RR 1.12, 95%CI 0.80-1.56). However, echinocandins appeared to be significantly safer than other forms of antifungal therapy (RR 0.79, 95%CI 0.73-0.86).ConclusionOur findings have shown that echinocandin monotherapy (micafungin, caspofungin) given intravenously are just as effective as other antifungals (amphotericin B, itraconazole) in the treatment of systemic candidiasis in immunocompromised patients. There appears to be similar benefits when using echinocandins compared to amphotericin B which has also been used as a broad-spectrum antifungal, while avoiding the severe adverse effects that amphotericin B causes, such as nephrotoxicity.     

Efficacy and safety of acupuncture in the treatment of depression: A systematic review of clinical research

As a common mental disorder, depression is one of the leading causes of disability around the world. Clinical studies have shown that acupuncture is an effective therapy without obvious side effects compared to limited efficacy and adverse reactions of drug therapy, cognitive behavioral therapy, and neuromodulation technology in treating depression. The objective of this review is to systematically evaluate whether acupuncture therapies for depression are safe and effective in order to provide a high-quality reference for clinical trials of acupuncture. A systematic search of the literature was carried out through bibliographic search engine PubMed. Subsequently, the study design, intervention methods, control group, results, and safety of acupuncture were analyzed. The results showed that acupuncture as an adjunct to antidepressants or as a single treatment can exert a positive impact on patients' depressive symptoms. Compared with antidepressants, acupuncture has the advantages of fast onset and long-term efficacy in the treatment of depression, and can enhance the efficacy of antidepressants. Moreover, the efficacy and safety of acupuncture in the treatment of depression maybe related to the qualification of the acupuncturist, the selection of acupoints, and intervention measures.     

Efficacy of empowerment strategies for patients with hypertension: A systematic review and meta-analysis

BackgroundCardiovascular disease has caused heavy health care burdens in many countries, and hypertension (HTN) is a well-known independent cardiovascular risk factor.ObjectiveTo assess the efficacy of empowerment strategies that affect systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), quality of life, and self-management behaviours for patients with hypertension.MethodsA literature search of the Cochrane Library, PubMed, MEDLINE, Embase, Web of Science, and several Chinese medical databases was performed. Study screening, quality assessment, data extraction, and meta-analysis were conducted according to Cochrane standards.ResultsEleven randomised controlled trials with 988 subjects were identified. Relative to control groups, the empowerment strategies showed significant decreases in SBP (the mean difference [MD] = 9.46, 95 % confidence interval [CI] = 6.36–12.55, p < 0.00001) and DBP (MD = 6.68, 95 % CI = 3.07–10.29, p = 0.0003). However, no significant difference was found in BMI (p = 0.05). Subgroup analysis showed significant differences in the improvement of both SBP and DBP among the various groups, regardless of the duration and type of interventions.DiscussionEmpowerment strategies can decrease both SBP and DBP in hypertension patients. However, its influence on patients’ BMI, quality of life, and self-management behaviour remains unclear.Practical valueEmpowerment strategies are useful for controlling the blood pressure of hypertension patients.     

Efficacy and safety of rituximab for relapsing-remitting multiple sclerosis: A systematic review and meta-analysis

Objective

To evaluate the efficacy and safety of rituximab for relapsing-remitting multiple sclerosis.

Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency

BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune disorder characterized by antibody deficiency and a decrease in serum IgG and IgA, IgM, or both levels at least 2 SDs below the mean for age and not attributed to other known immunologic disorders. These patients often present with frequent and severe episodes of pneumonia before diagnosis. The standard treatment, intravenous immunoglobulin (IVIG), has been available for the past 20 years. No large-scale study has compared the incidence of pneumonia in these patients before and after IVIG treatment. OBJECTIVE: The aim of this study was to document the effectiveness of intravenous immunoglobulin treatment on the incidence of pneumonia in patients with CVID. METHODS: We performed chart reviews and interviews of patients with laboratory-confirmed CVID seen at our clinical center. The number of episodes of pneumonia was documented before and after treatment with immunoglobulin replacement therapy. RESULTS: The histories of 50 patients were reviewed (mean current age, 42 +/- 16.3 years; age range, 10-78 years; 20 male and 30 female patients). Forty-two (84%) of the 50 patients with CVID had pneumonia at least once before receiving immunoglobulin treatment, and 11 of 42 of these patients had multiple episodes. After treatment with gamma globulin over a mean period of 6.6 +/- 5.2 years (range, <1-20 years), the number of patients experiencing pneumonia significantly decreased to 11 (22%) of 50. In most cases these patients had pneumonia in the first year of immunoglobulin treatment. CONCLUSION: The treatment of CVID with IVIG significantly reduces the incidence of pneumonia.