Abstract

BACKGROUND Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis. METHODS In this prospective randomized controlled monocentric study, we assessed safety and efficacy of therapy with IA or TPE in patients with neurological autoimmune diseases. Treatment response was assessed using various neurological scores as well by measuring immunoglobulin and cytokine concentrations. Clinical outcome was evaluated by application of specific scores for the underlying diseases. RESULTS A total of 32 patients were analyzed. Among these, 19 patients were treated with TPE and 13 patients with IA. IA and TPE therapy showed a comparable significant treatment response. In patients with MS and NMOSD, mean EDSS before and after treatment showed a significant reduction after treatment with IA. We observed a significant reduction of the pro-inflammatory cytokines IL-12, lL-17, IL-6, INF-γ, and tumor necrosis factor alpha during IA treatment, whereas this reduction was not seen in patients treated with TPE. CONCLUSIONS In summary, both IA and TPE were effective and safe procedures for treating neurological autoimmune diseases. However, there was a trend towards longer therapy response in patients treated with IA compared to TPE, possibly related to a reduction in plasma levels of pro-inflammatory cytokines seen only in the IA-treated group.

Abstract

BACKGROUND Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH. METHODS Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality. RESULTS Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61), P = 0.01, I(2) = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55), P = 0.042, I(2) = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95), P = 0.001, I(2) = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70), P = 0.038, I(2) = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39), P < 0.0001, I(2) = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95), P = 0.16, I(2) = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41), P = 0.70, I(2) = 75.5%). CONCLUSIONS Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.

Abstract

OBJECTIVE To assess through systematic review and meta-analysis whether plasma exchange (PE) is associated with prognosis in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. METHODS A systematic search of PubMed, MEDLINE, Embase, and CENTRAL databases from inception to 17 June 2020 was conducted. Ongoing or unpublished trials were also searched in ClinicalTrials.gov and the World Health Organization trials portal. Randomised controlled trials (RCTs) comparing PE vs. non-PE in AAV patients (microscopic polyangiitis [MPA], granulomatosis with polyangiitis [GPA], or eosinophilic granulomatosis with polyangiitis [EGPA]) were included. The combined risk ratio (RR) was calculated by the random-effects model using the Mantel-Haenszel method. Heterogeneity was measured using the I(2) statistic. Primary outcomes were mortality, clinical remission (CR), and adverse events (AEs). RESULTS Four RCTs comparing PE vs. no PE (N = 827) and 1 RCT comparing PE vs. pulse steroid treatment (N = 137) were included. All participants were MPA or GPA patients (no EGPA patients). PE was not associated with main primary outcomes compared with no PE (mortality RR 0.93 [95% confidence interval {CI} 0.70-1.24], I(2) = 0%; CR RR 1.02 [95% CI 0.91-1.15], I(2) = 0%; and AE RR 1.10 [95% CI 0.73-1.68], I(2) = 37%) or pulse steroid (mortality RR 0.99 [95% CI 0.71-1.37]; CR [the Birmingham Vasculitis Activity score] mean difference - 0.53 [95% CI - 1.40-0.34]; and AE RR 1.05 [95% CI 0.74-1.48]). Focusing on the early treatment phases, PE was associated with a reduction in end-stage renal disease incidence compared with both no PE (PE 1/43 vs. no PE 10/41; RR 0.14 [0.03-0.77] at 3 months) and pulse steroid (PE 11/70 vs. pulse steroid 23/67; RR 0.46 [0.24-0.86] at 3 months). CONCLUSION We carried out a systematic review and meta-analysis targeting all AAV patients, including MPA, GPA, and EGPA. In AAV patients, performing PE was not associated with the risk of mortality, CR, and AE. No RCT exists evaluating the efficacy of PE for EGPA; hence, this is required in the future. The results may affect the development of guidelines for AAV and may indicate the direction of future clinical research on AAV. TRIAL REGISTRATION UMIN R000045239 , PROSPERO CRD42020182566 .

Abstract

AIMS: The therapeutic effect of plasma exchange (PLEX) combined with conventional treatment in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. MATERIALS AND METHODS We searched PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure for randomized controlled trials (RCTs) and cohort studies that compared PLEX added to conventional therapy with conventional therapy only in active AAV. RESULTS 19 studies were included for the meta-analysis. Compared with the conventional therapy group, the PLEX group had a significantly reduced risk of end-stage renal disease (ESRD) at 3 months (odds ratio (OR) = 0.32, 95% confidence interval (CI) = 0.16 - 0.66, p = 0.002, I2 = 0%), and the ANCA titerwas also decreased (OR = 40.99, 95% Cl = 23.56 - 58.43, p < 0.00001, I2 = 42%). The plasma and non-plasma exchange groups had no substantial differences in terms of short- and long-term outcomes, including all-cause mortality, ESRD risk at 12 months and 5 years, remission rate, serum creatine levels, or serious adverse events. CONCLUSION PLEX therapy was not associated with favorable long-term outcomes, although the results showed benefits in the incidence of ESRD rate at 3 months and ANCA titers in patients with AAV. No advantage of PLEX added to conventional therapy on mortality and complete remission was observed in patients with diffuse alveolar hemorrhage. Further high-quality multicenter RCTs with a high number of participants are required to assess the potential efficacy of PLEX in active AAV.

Abstract

BACKGROUND Neuromyelitis optica spectrum disorders (NMOSDs) are autoimmune astrocytopathies with predominant involvement of the optic nerves and spinal cord. The current management is high-dose intravenous methylprednisolone, followed by apheresis therapy if it fails. We aimed to investigate plasma exchange (PE) benefits in corticosteroid-refractory NMOSDs. METHODS From Embase, PubMed, Cochrane, Web of Science, and Clinical Trials, we identified PE-based studies published between Jan 2007 and Dec 2019. We pooled the information of these studies in a binomial meta-analysis. We investigated the factors affecting the efficacy of PE and its adverse events. The effectiveness of PE was assessed using the Expanded Disability Status Scale (EDSS). The timing of PE initiation was assessed using Spearman correlation analysis. RESULTS We included 561 records and identified 8 observational studies, including 228 NMOSD patients. The mean time to the initiation of PE was 11 days, and the average volume of each exchange was 1.5-2 L. PE treatment reduced the mean EDSS score by -1.04 (95% CI, -1.44 to -0.64). The initiation time of PE significantly affected the outcome (EDSS reduction) (P = 0.01; 95% CI, -1.30 to 0.28). In the ≤ 7-day and 8-23-day groups, the mean EDSS decreased by 0.64 (95% CI, -0.93 to -0.34) and 1.41 (95% CI, -1.79 to -1.02), respectively. In addition, PE showed the same efficacy for alleviating the symptoms of NMOSDs, regardless of the day between 8 to 23 days on which it was performed (P = 0.29). Thirty-five (20.8%) of the 168 patients had adverse events. CONCLUSION PE can ameliorate severe NMOSDs. PE effectiveness was associated with the duration between disease and the initiation of PE, and the optimal timing for PE initiation is 8 to 23 days after the onset of the disease.

Abstract

BACKGROUND Plasma exchange (PLEX) in addition to standard immunosuppressive treatment in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AVV) remains controversial. The aim of this study is to evaluate the effect of PLEX on AVV outcomes. METHODS Literature search was performed using Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov databases, and Google Scholar. The statistical meta-analysis and leave-one-out analysis were conducted using the Review Manager 5.3 and Open Meta-Analyst software, respectively. RESULTS Ten studies were included in the meta-analysis comprising 1235 patients; 633 received conventional treatment and 602 were treated with PLEX in conjunction with induction therapy. PLEX was not associated with lower rates of either mortality at 3 (RR: 0.79, 95% CI: 0.19-3.25) and 12 months (RR: 0.73, 95% CI: 0.40-1.34) or ESRD at 3 (RR: 0.30, 95% CI: 0.30-2.42) and 12 months (RR: 1.32, 95% CI: 0.53-3.25). Similarly, no differences were captured concerning disease relapses (RR: 0.92, 95% CI: 0.62-1.36), the incidence of infections (RR: 1.05, 95% CI: 0.63-1.76), and severe adverse effects (RR: 1.04, 95% CI: 0.59-1.81). Time-to-event analysis revealed lower incidence of ESRD (HR: 0.71, 95% CI: 0.55-0.92) among patients who received PLEX, while the overall mortality was similar (HR: 0.96, 95% CI: 0.72-1.29) between the two groups. CONCLUSION The present meta-analysis does not support the wide use of PLEX for the management of AAV in routine clinical practice. Future well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX. Key Points • PLEX is not widely recommended for the management of ANCA-associated vasculitis. • PLEX performance may reduce the overall incidence of ESRD in severe ANCA-associated vasculitis. • Well-designed randomized controlled trials focusing on specific disease-related manifestations are necessary to reach firm conclusions about the potential efficacy of PLEX on AAV-related outcome.

Abstract

BACKGROUND More effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS We conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m(2) of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD). RESULTS Death from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups. CONCLUSIONS Among patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).

Abstract

INTRODUCTION Systemic lupus erythematosus (SLE) is a complex autoimmune pathology that can involve any organ. Lupus-related acute pancreatitis (AP) is, together with lupus mesenteric vasculitis, an important cause of SLE-induced acute abdominal pain. METHODS A literature search was conducted using the terms "Pancreatitis" and "Lupus Erythematosus, Systemic" on PubMed/Medline and Web of Science from January 2007 to January 2020. Clinical characteristics, diagnostic approach, and treatment principles in SLE-related AP are presented in this review. RESULTS Mainly retrospective reports were identified. The reported incidence of SLE-associated AP ranges from 0.9 to more than 5% of patients. A total of 264 SLE patients were found in the selected research, with a net female predominance (sex ratio 9:1) and mean age of 31.4 years. Abdominal pain was virtually present in all cases. AP occurrence was more frequent in SLE patients with short disease duration, high activity scores, and multiorgan involvement. The AP definition was based on currently available guidelines and after exclusion of any other known causes (including iatrogenic, i.e. drugs), a diagnosis of "idiopathic" SLE-related AP might be sustained. Management is difficult, as there is no standardized therapeutic approach. Of note, glucocorticoid use remains still controversial as, especially for high doses, subsequent pancreatic injury may occur. Monitoring serum lipase levels after high dose steroids might be considered. One study reported beneficial prognostic effect of plasma exchange. Moreover, AP in SLE might raise awareness about macrophage activation syndrome association. Mortality up to one third of AP cases in SLE was reported. CONCLUSION The SLE-related AP is a rare, but severe, life-threatening complication. Corticosteroids must be used with caution. Plasma exchange could be considered in selected cases.

Abstract

OBJECTIVE We performed a systematic review and meta-analysis to evaluate the efficacy and safety of therapeutic plasma exchange (TPE) in adult patients with autoimmune hemolytic anemia (AIHA). METHODS A search of major English and Chinese databases for randomized controlled trials (RCTs) comparing the use of TPE against no TPE in adult AIHA patients was performed. Outcomes were remission incidence, hematological parameters (ie, hemoglobin count, red blood cell count, reticulocyte percentage, total bilirubin, and hematocrit) and adverse event incidence. RESULTS Thirteen RCTs containing 906 patients were included. A majority of RCTs were given an unclear risk of bias. TPE was associated with increased remission incidence (risk ratio [RR] = 1.22, 95% confidence interval [CI] = 1.15-1.30) and improved hematological parameters. TPE was also associated with an insignificant increase in adverse event incidence (RR = 1.12, 95% CI = 0.68 to 1.86). Publication bias was detected for remission incidence and reticulocyte percentage, and it may have led to an overestimation of beneficial improvements in reticulocyte percentage. CONCLUSION TPE was associated with both increased remission incidence and improved hematological parameters. It is capable of improving short-term hematological parameters to stabilize acute AIHA onset. Our results should be interpreted with caution due to the unclear risk of bias and the presence of publication biases. We were not able to determine the treatment effects for cold and warm AIHA separately due to a lack of subgroup data. Future RCTs incorporating larger sample sizes with subgroup data for warm and cold AIHA are needed to validate our findings and establish subgroup efficacy and safety.

Abstract

OBJECTIVE To conduct systematic review and meta-analysis for the efficacy of therapeutic plasma exchange (TPE) for neuromyelitis optica spectrum disorder (NMOSD) with an acute attack. METHODS Systematic review was performed using EMBASE and OVID/Medline database. The eligible studies must be the studies of NMOSD patients treated with TPE during the acute phase. They must report treatment outcomes using either Expanded Disability Status Scale (EDSS) or visual acuity (VA) before and after the therapy. Pooled mean difference (MD) was then calculated by combining MDs of each study using the random-effects model. RESULTS Fifteen studies were identified; eleven with 241 NMOSD patients reported EDSS outcome and four studies with 103 NMOSD reported visual outcomes. The meta-analysis demonstrated a significantly decreased in EDSS after TPE treatment for NMOSD with an acute attack with the pooled MD of 0.83 (95% CI, 0.26-1.40; I(2) 69%) comparing pretreatment to immediate posttreatment and 2.13 (95% CI, 1.55-2.70; I(2) 31%) comparing pretreatment to posttreatment at 6 months to 1-year follow-up. Unfortunately, only one of the four studies evaluating visual outcomes reported standard deviation in association with mean LogMAR; therefore, the meta-analysis cannot be conducted. Nonetheless, all studies consistently demonstrated the benefit of TPE with improved VA and/or LogMAR after treatment. INTERPRETATION This systematic review and meta-analysis showed the benefit of TPE during the NMOSD attack with a significantly improved disability status immediately after treatment and during follow-up.