Apheresis Technique for Acute Hyperlipidemic Pancreatitis: A Systemic Review and Meta-Analysis
Lin YF, Yao Y, Xu Y, Huang HB
Digestive diseases and sciences. 2022
BACKGROUND The apheresis technique is increasingly used in patients with hypertriglyceridemia-induced pancreatitis (HTGP), while its role in this context is still not well established. Thus, we aimed to evaluate the clinical outcomes of an apheresis therapy compared to usual care in such a patient population. METHODS We searched PubMed, Embase, and Cochrane library databases up to July 10, 2021. Studies were included if they focused on HTGP treated with or without apheresis technique. We used the Newcastle-Ottawa Scale to assess the quality of the included studies. The primary outcome was the mortality rate. We also explored the heterogeneity, sensitivity analysis, subgroup analysis, and publication bias. RESULTS Sixteen observational studies with 1476 adults were included. The overall quality of included studies was moderate. Despite better TG level reduction with apheresis therapy (mean difference [MD], 12.27 mmol/L, 95% CI, 3.74 to 20.81; I(2) = 78%; P = 0.005), use of apheresis did not reduce the mortality (odds ratio [OR], 1.01; 95% CI, 0.65 to 1.59; P = 0.95) compared with usual care. This result was further confirmed by sensitivity analysis, subgroup analysis. The length of stay in hospital (MD, 0.96 days; 95% CI, - 1.22 to 3.14; I(2) = 70%; P = 0.39) and most complications were similar between the groups, while hospital cost was significantly higher in the apheresis group. CONCLUSIONS The apheresis technique did not decrease the mortality in HTGP patients compared with usual care. Until the results of high-quality RCTs are known, these findings do not support the routine use of the apheresis technique in such a patient population.
Patients with hypertriglyceridemia-induced pancreatitis, (16 studies, n= 1,476).
Despite better triglycerides level reduction with apheresis therapy (mean difference [MD], 12.27 mmol/L), use of apheresis did not reduce the mortality compared with usual care. The length of stay in hospital (MD, 0.96 days) and most complications were similar between the groups, while hospital cost was significantly higher in the apheresis group. The overall quality of included studies was moderate.
Plasmapheresis compared with conventional treatment for hypertriglyceridemia-induced acute pancreatitis: A systematic review and meta-analysis
Yan LH, Hu XH, Chen RX, Pan MM, Han YC, Gao M, Liu H
Journal of clinical apheresis. 2022
BACKGROUND The treatment of acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) remains controversial with regard to plasmapheresis vs conventional treatment. We reviewed relevant articles to explore the efficacy of plasmapheresis in the management of HTG-induced AP. METHODS We systematically reviewed studies that compared plasmapheresis with conventional treatment for HTG-induced AP using three databases: PubMed, Embase, and Cochrane Library, as well as relevant references. The primary outcomes were 24 h triglyceride reduction rate and in-hospital mortality. RESULTS A total of 791 articles were retrieved. Finally, 15 observational studies (1080 participants) were included, most of which were historical cohort studies. Compared with conventional treatment, plasmapheresis assisted in the reduction of serum triglyceride (TG) levels in the first 24 h after hospital admission (standardized mean difference [SMD]: 0.58; 95% confidence interval [CI]: 0.17 to 0.99; P = 0.005). However, it resulted in increased hospitalization costs (thousand yuan) (weighted mean difference [WMD]: 24.32; 95% CI: 12.96 to 35.68; P < 0.001). With regard to in-hospital mortality, although the mortality rate in the plasmapheresis group was higher than that in the conventional treatment group (relative risk [RR]: 1.74; 95% CI: 1.03 to 2.94; P = 0.038), the result was disturbed by confounding factors as per the subgroup and sensitivity analysis, as well as trial sequential analysis (TSA). No significant differences were found in other outcomes, including systematic complications, local complications, the requirement for surgery, and hospitalization duration. CONCLUSION The effect of plasmapheresis in HTG-induced AP is not superior to that of conventional treatment, even resulting in a greater economic burden to patients and health care system. High quality randomized control trials are required to obtain a more a definitive understanding of this issue.
Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta-analysis
Kiss S, Németh D, Hegyi P, Földi M, Szakács Z, Erőss B, Tinusz B, Hegyi PJ, Sarlós P, Alizadeh H
BMJ open. 2021;11(5):e042374
OBJECTIVE The goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy. DESIGN Systematic review and meta-analysis. METHODS We searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses. RESULTS A total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I(2)=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I(2)=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I(2)=84.2%). CONCLUSION GMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone. PROSPERO REGISTRATION NUMBER CRD42019134050.
Novel Leucocyte/Thrombocyte Apheresis for Induction of Steroid-Free Remission in Ulcerative Colitis: A Controlled Randomized Pilot Study
Kruis W, Nguyen P, Morgenstern J, Ramlow W, Dignass A, Stallmach A, Drebber U
Journal of Crohn's & colitis. 2019
BACKGROUND AND AIMS In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. METHODS This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. RESULTS Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 +/- 5.3 to 3.8 +/- 3.7 mg/L at 12 weeks in group A and increased from 5.2 +/- 6.0 to 6.3 +/- 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. CONCLUSIONS In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids. CIV-12-01-003581.
Shorter Relapse-Free Period after Leukocyte Removal Therapy in Younger than Older Patients with Ulcerative Colitis
Yamasaki S, Sakata Y, Yoshida H, Shirai S, Tanaka Y, Nakano R, Yukimoto T, Tsuruoka N, Shimoda R, Fukuda M, et al
BACKGROUND Leukocyte removal therapy (LRT) is an effective treatment for active ulcerative colitis (UC). The present study was performed to evaluate the relapse-free period after LRT and identify risk factors for relapse. METHODS In total, 94 patients who underwent first-time LRT for remission of moderate to severe UC from April 2004 to March 2016 were enrolled in the present study. The patients were randomly assigned to one of 2 treatments: leukocytapheresis (LCAP; n = 43) or granulocyte and monocyte/macrophage adsorptive apheresis (GMA; n = 51). The 5-year cumulative relapse-free rate and risk factors for relapse were evaluated. RESULTS The therapeutic response rate was 82% for GMA and 70% for LCAP without a statistically significant difference. The 5-year relapse-free rate was 34.7% in the LRT group. The 5-year relapse-free rate in patients aged > 40 years was 49.9%, which was significantly higher than that in patients aged ≤40 years (22.9%, p < 0.01). The relapse-free period was longer in the older than younger patients. CONCLUSIONS The relapse-free period after LRT was examined in patients with UC, and 34.7% of patients achieved clinical remission within a 5-year period. The risk factor for early relapse after LRT was younger age.
Addition of granulocyte/monocyte apheresis to oral prednisone for steroid-dependent ulcerative colitis: A randomized, multicentre, clinical trial
Domenech E, Panes J, Hinojosa J, Annese V, Magro F, Sturniolo G C, Bossa F, Fernandez F, Gonzalez-Conde B, Garcia-Sanchez V, et al
Journal of Crohn's & Colitis. 2018;12((6):):687-694
Background and Aims: Steroid-dependency occurs in up to 30% of patients with ulcerative colitis (UC). In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis (GMA) to oral prednisone in patients with steroid-dependent UC. Methods: Randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone (40mg/day and tapering) to prednisone alone in patients with active, steroid-dependent UC (Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation). Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary end point was steroid-free remission (defined as a total Mayo score ≤2, with no subscore >1) at week 24, with no reintroduction of corticosteroids. Results: One hundred and twenty-three patients were included (63 GMA group, 62 prednisone alone). In the ITT analysis, steroid-free remission at week 24 was achieved in 13% (95%CI 6-24) in the GMA group and 7% (95%CI 2-16) in the control group (P=0.11). In the GMA group, time to relapse was significantly longer (HR 1.7 [1.16-2.48], P=0.005) and steroid-related adverse events were significantly lower (6% vs. 20%, P<0.05). Conclusions: In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse. ClinicalTrials.gov ID: NCT00702611.
Randomised, Double-blind, Placebo-controlled Trial of CCR9-targeted Leukapheresis Treatment of Ulcerative Colitis Patients
Eberhardson M, Karlen P, Linton L, Jones P, Lindberg A, Kostalla MJ, Lindh E, Oden A, Glise H, Winqvist O
Journal of Crohn's & Colitis. 2017;11((5)):534-542.
Background and Aims: Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DRhi] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-alpha. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response. Methods: Patients with ulcerative colitis were treated every second day with leukapheresis during five sessions with a C-C chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column. Results: No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group [p = 0.0391] whereas no statistically significant change was seen in the placebo group [p = 0.4688]. There was a significant decrease of HLA-DRhi monocytes in the active group compared with the placebo group when corrected for the imbalance in weight between the groups [p = 0.0105]. Mayo score decreased in the active group [p = 0.0156] whereas the change in the placebo group was not significant [p = 0.1250]. Mayo score ≤ 3 was observed in five out of 14 patients [35.7%] in the active group compared with one out of eight [12.5%] receiving placebo. The number of responders in the active treatment group was eight out of 14 patients [57.1%], whereas in the corresponding placebo group three out of eight patients [37.5%] responded to placebo. A dose-response correlation was observed between the blood volume processed and clinical outcome. Conclusion: This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.
Randomized, double-blind, placebo-controlled trial of CCR9-targeted leukapheresis treatment of ulcerative colitis patients
Eberhardson M, Karlen P, Linton L, Jones P, Lindberg A, Kostalla MJ, Lindh E, Oden A, Glise H, Winqvist O
Journal of Crohn's & Colitis. 2016;11((5):):534-542
BACKGROUND AND AIMS Ulcerative colitis patients display increased number of circulating pro-inflammatory HLA-DRhi monocytes expressing high levels of the gut homing chemokine receptor CCR9 and TNF-alpha. The aim of this first-in-man double blind randomized placebo controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis with regards to safety, tolerability and immunological response. METHODS Patients with ulcerative colitis were treated every second day with leukapheresis during 5 sessions with CCL25 (CCR9 ligand) column or a placebo column. RESULTS No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group (p=0.0391) while no statistically significant change was seen in the placebo group (p=0.4688). There was a significant decrease of HLA-DRhi monocytes in the active group compared to the placebo group when corrected for the imbalance in weight between the groups (p=0.0105). Mayo score decreased in the active group (p=0.0156) whereas the change in the placebo group was not significant (p=0.1250). Mayo score ≤3 was observed in five out of 14 patients (35.7%) in the active group compared to one out of eight (12.5%) receiving placebo. The number of responders in the active treatment group was eight out of 14 patients (57.1%), whereas in the corresponding placebo group three out of eight patients (37.5%) responded to placebo. A dose response correlation was observed between the blood volume processed and clinical outcome. CONCLUSION This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.
An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease
Yoshimura N, Yokoyama Y, Matsuoka K, Takahashi H, Iwakiri R, Yamamoto T, Nakagawa T, Fukuchi T, Motoya S, Kunisaki R, et al
BMC Gastroenterology. 2015;15((1)):163.
BACKGROUND Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. METHODS In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). RESULTS Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 +/- 5.3 days in the weekly GMA and 21.7 +/- 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/muL to 6950/muL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. CONCLUSIONS In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.
Granulocyte/monocyte adsorptive apheresis in moderate to severe ulcerative colitis - effective or not?
Kruis W, Nguyen P, Morgenstern J
BACKGROUND AND AIMS Adsorptive granulocyte/monocyte apheresis (GMA) has shown promising efficacy in the treatment of patients with ulcerative colitis (UC). But a sham-controlled study was negative. A post-hoc analysis of this trial may haul out patients responding to GMA. METHODS A total of 168 UC patients with a disease activity (DAI) between 6 and 11 were enrolled in this study. Out of 168 patients, 112 received GMA and 56 sham apheresis. The basis for this post hoc analysis is the clinical study report issued by Otsuka America Pharmaceutical. RESULTS Baseline histology was available for 165 patients. Only 38% (63 of 165) of patients showed microscopic erosion/ulceration (group P). The remaining 62% of patients did not show microscopic erosion/ulceration (group A). The patients in group P showed significantly higher DAI, flexible proctosigmoidoscopy score and neutrophil infiltration into the colonic mucosa than those in group A (p = 0.0132, p = 0.0243 and p < 0.0001, respectively). Likewise, group P patients had a significantly (p = 0.0275) higher remission rate (11 of 46; 23.9%) when treated with GMA than with sham procedure (0 of 17; 0%). CONCLUSIONS Patients in group P who had more active UC than those in group A showed clear clinical efficacy in response to GMA. We believe that true DAI should be specified for further randomized controlled trials. © 2015 S. Karger AG, Basel.