-
The American Journal of Gastroenterology Sep 2023Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early symptomatic remission with approved therapies.
METHODS
Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values.
RESULTS
On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85-6.27), 4 (range of RR, 1.78-2.37), and 6 (range of RR, 1.84-2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients.
DISCUSSION
In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.
Topics: Adult; Humans; Colitis, Ulcerative; Tumor Necrosis Factor-alpha; Network Meta-Analysis; Adalimumab; Ustekinumab; Treatment Outcome
PubMed: 36976548
DOI: 10.14309/ajg.0000000000002263 -
EClinicalMedicine Mar 2023Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but...
BACKGROUND
Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population.
METHODS
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.
FINDINGS
The systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints.
INTERPRETATION
In this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies.
FUNDING
None.
PubMed: 36864986
DOI: 10.1016/j.eclinm.2023.101866 -
Journal of Vascular and Interventional... Aug 2021To assess the efficacy and safety of a catheter-directed hemorrhoidal dearterialization technique for the management of hemorrhoidal bleeding. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To assess the efficacy and safety of a catheter-directed hemorrhoidal dearterialization technique for the management of hemorrhoidal bleeding.
MATERIALS AND METHODS
A systematic review and meta-analysis of pubmed, cochrane, and scopus databases was conducted according to the preferred reporting items for systematic reviews and meta-Analysis (PRISMA) guidelines. Clinical studies reporting on catheter-directed hemorrhoidal dearterialization for rectal bleeding were analyzed.
RESULTS
Fourteen studies (n = 362) were identified. The mean maximum follow-up duration was 12.1 months (SD, 7.31; range, 1-28; median, 12), and the mean length of hospital stay was 1.5 days (SD, 1.1; range, 0-2.5). The mean technical success was 97.8% (SD, 3.5), and the mean clinical success was 78.9% (SD, 10.5). A statistically significant reduction in the french bleeding score before and after embolization was noted (P = .004). In subgroup analysis, when the coils-only group was compared with the coils and particles group, the average rebleeding rate was 21.5% (n = 111; SD, 18.2; range, 0%-44%) versus 10.05% (N = 108; SD, 4.8; range, 5%-15.7%), respectively (P < .0001). No bowel ischemia/necrosis or anorectal complications were reported.
CONCLUSIONS
The current preliminary clinical evidence suggests that catheter-directed hemorrhoidal dearterialization is an effective and safe procedure for the treatment of hemorrhoidal bleeding. The standardization of the technique and the generation of higher level evidence will be required to compare this minimally invasive procedure with more invasive surgical options for patients with grades I-III hemorrhoids and chronic bleeding.
Topics: Catheters; Hemorrhoidectomy; Hemorrhoids; Humans; Ligation; Rectum; Treatment Outcome
PubMed: 33971251
DOI: 10.1016/j.jvir.2021.03.548 -
Journal of Crohn's & Colitis Apr 2018The impact of vedolizumab, a gut-selective monoclonal antibody, on postoperative outcomes is unclear. This study aimed to assess the impact of preoperative vedolizumab... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The impact of vedolizumab, a gut-selective monoclonal antibody, on postoperative outcomes is unclear. This study aimed to assess the impact of preoperative vedolizumab treatment on the rate of postoperative complications in patients with inflammatory bowel disease [IBD] undergoing abdominal surgery.
METHODS
A systematic search of multiple electronic databases from inception until May 2017 identified studies reporting rates of postoperative complications in vedolizumab-treated IBD patients compared to no biologic exposure or anti-tumor necrosis factor (anti-TNF) treated IBD patients. Outcomes of interest included postoperative infectious complications and overall postoperative complications. Pooled risk ratios and 95% confidence intervals were estimated using the random-effects model.
RESULTS
Five studies comprising 307 vedolizumab-treated IBD patients, 490 anti-TNF-treated IBD patients and 535 IBD patients not exposed to preoperative biologic therapy were included. The risk of postoperative infectious complications (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.37-2.65) and overall postoperative complications [RR 1.00, 95% CI 0.46-2.15] were not significantly different between vedolizumab-treated patients and those who received no preoperative biologic therapy. In addition, the risk of postoperative infectious complications [RR 0.99, 95% CI 0.34-2.90] and overall postoperative complications [RR 0.92, 95% CI 0.44-1.92] were not significantly different between vedolizumab-treated vs anti-TNF-treated patients.
CONCLUSIONS
Preoperative vedolizumab treatment in IBD patients does not appear to be associated with an increased risk of postoperative infectious or overall postoperative complications compared to either preoperative anti-TNF therapy or no biologic therapy. Future prospective studies which include perioperative drug level monitoring are needed to confirm these findings.
Topics: Antibodies, Monoclonal, Humanized; Gastrointestinal Agents; Humans; Infections; Odds Ratio; Postoperative Complications; Preoperative Care; Tumor Necrosis Factor-alpha
PubMed: 29718245
DOI: 10.1093/ecco-jcc/jjy022 -
Colorectal Disease : the Official... Jul 2016The introduction of anti-tumour necrosis factor (anti-TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively... (Comparative Study)
Comparative Study Meta-Analysis Review
AIM
The introduction of anti-tumour necrosis factor (anti-TNF; infliximab and adalimumab) has changed the management of Crohn's perianal fistula from almost exclusively surgical treatment to one with a much larger emphasis on medical therapy. The aim of this systematic review was to provide an overview of the success rates of setons and anti-TNF for Crohn's perianal fistula.
METHOD
Studies evaluating the effect of setons and anti-TNF on Crohn's perianal fistula were included. Studies assessing perianal fistula in children, rectovaginal and rectourinary fistulae were excluded. The primary end-point was the fistula closure rate. Partial closure and recurrence rates were secondary end-points.
RESULTS
Ten studies on seton drainage were included (n = 305). Complete closure varied from 13.6% to 100% and recurrence from 0% to 83.3%. In 34 anti-TNF studies (n = 1449), complete closure varied from 16.7% and 93% (partial closure 8.0-91.2%) and recurrence from 8.0% to 40.9%. Four randomized controlled trials (n = 1028) comparing anti-TNF with placebo showed no significant difference in complete or partial closure in meta-analysis (risk difference 0.12, 95% CI -0.06 to 0.30 and 0.09, 95% CI -0.23 to 0.41, respectively). Subgroup analysis (n = 241) showed a significant advantage for complete fistula closure with anti-TNF in two trials with follow-up > 4 weeks (46% vs 13%, P = 0.003 and 30% vs 13%, P = 0.03). Of four included cohort studies, two revealed a significant difference in response in favour of combined treatment (P = 0.001 and P = 0.014).
CONCLUSION
Closure and recurrence rates after seton drainage as well as anti-TNF vary widely. Despite a large number of studies, no conclusions can be drawn regarding the preferred strategy. However, combination therapy with (temporary) seton drainage, immunomodulators and anti-TNF may be beneficial in achieving perianal fistula closure.
Topics: Adalimumab; Adult; Cohort Studies; Crohn Disease; Drainage; Female; Gastrointestinal Agents; Humans; Infliximab; Male; Perineum; Randomized Controlled Trials as Topic; Rectal Fistula; Recurrence; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 26921847
DOI: 10.1111/codi.13311 -
Alimentary Pharmacology & Therapeutics Oct 2014The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. (Review)
Review
BACKGROUND
The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required.
AIM
To review systematically the literature to assess fistula healing rates with medical treatment (anti-TNF-α therapies ± immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD).
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature.
RESULTS
Twenty-four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group.
CONCLUSIONS
Combined surgical and medical (anti-TNF-α ± immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing.
Topics: Combined Modality Therapy; Crohn Disease; Humans; Immunologic Factors; Rectal Fistula; Treatment Outcome; Tumor Necrosis Factor-alpha
PubMed: 25115149
DOI: 10.1111/apt.12906 -
Journal of Crohn's & Colitis Apr 2024Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fistulas are a debilitating complication of Crohn's disease [CD]. We conducted a systematic review to assess the efficacy of medical therapies for fistulizing CD.
METHODS
MEDLINE, Embase, and CENTRAL were searched on May 26, 2022, for randomized controlled trials [RCTs] of pharmacological therapy in adults with fistulizing CD. The primary outcome was induction and maintenance of fistula response. Pooled risk ratios [RRs] and 95% confidence intervals [CIs] were calculated. GRADE was used to assess the certainty of evidence.
RESULTS
Thirty-eight RCTs were included. Nineteen trials [50%] exclusively involved perianal fistula. The remaining studies included some participants with non-perianal fistula. Pooled RRs for anti-tumour necrosis factor [TNF] agents were not statistically significant for induction [RR 1.36, 95% CI 0.97-1.91] or maintenance of fistula response [RR 1.48, 95% CI 0.97-2.27]. However, in a sensitivity analysis of studies with fistula response as the primary outcome, anti-TNFs were superior to placebo for induction [RR 1.94, 95% CI 1.10-3.41] and maintenance [RR 1.88, 95% CI 1.23-2.88] of fistula response. Oral small molecules [RR 2.56, 95% CI 1.18-5.53] and mesenchymal stem cell [MSC] therapy [RR 1.26, 95% CI 1.01-1.57] were effective for induction of fistula response. Ustekinumab was associated with maintenance of fistula response [RR 1.80, 95% CI 1.04-3.11]. Vedolizumab was not superior to placebo. The certainty of evidence ranged from very low to moderate.
CONCLUSION
Very low- to moderate-certainty evidence suggests that anti-TNF therapy, oral small molecules, ustekinumab, and MSCs are effective for perianal fistulizing CD. Dedicated fistula studies evaluating biologics and small molecules are needed.
Topics: Humans; Crohn Disease; Rectal Fistula; Gastrointestinal Agents; Intestinal Fistula; Randomized Controlled Trials as Topic
PubMed: 37933849
DOI: 10.1093/ecco-jcc/jjad185 -
JGH Open : An Open Access Journal of... Jun 2020Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While... (Review)
Review
Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While rates of clinical response and remission are well characterized in literature, magnetic resonance imaging (MRI) outcomes remain less so. This is despite previous studies demonstrating the persistence of fistula tracts on MRI, in spite of clinical healing, suggesting radiological markers of improvement may be more accurate. The aims of this study were to systematically review the literature for all studies reporting on MRI outcomes following biological therapy and to compare rates of radiological healing to clinical remission. A search was performed according to the Preferred Reporting Items For Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles were included, with a total sample size of 259 patients. Of these 259 patients, 47% achieved clinical remission following induction therapy and 42% following a median of 52 weeks' maintenance therapy. Out of the 259 patients, 7% achieved radiological healing in the short term and 25% in the long term. The odds ratio of MRI clinical healing was 0.10 (95% confidence interval [CI], 0.02-0.39) and 0.43 (95% CI, 0.26-0.71), respectively, at those corresponding time points. MRI healing of perianal fistulizing Crohn's, while arguably a more accurate assessment of treatment response, is significantly less common than clinical remission. Heterogeneity exists in the definition of radiological and clinical response, leading to variation in reported rates. Further studies, directly comparing the long-term outcomes of patients achieving clinical remission and MRI healing are required, to better inform the role of MRI follow up in clinical practice.
PubMed: 32514434
DOI: 10.1002/jgh3.12295 -
Early results and complications of prostatic arterial embolization for benign prostatic hyperplasia.World Journal of Urology May 2016To review current knowledge on clinical outcomes and peri-operative complications of prostatic arterial embolization (PAE) in patients treated for lower urinary tract... (Review)
Review
PURPOSE
To review current knowledge on clinical outcomes and peri-operative complications of prostatic arterial embolization (PAE) in patients treated for lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO).
METHODS
A systematic review of the literature published from January 2008 to January 2015 was performed on PubMed/MEDLINE.
RESULTS
Fifty-seven articles were identified, and four were selected for inclusion in this review. Only one randomized clinical trial compared transurethral resection of the prostate (TURP) to PAE. At 3 months after the procedure, mean IPSS reduction from baseline ranged from 7.2 to 15.6 points. Mean urine peak-flow improvement ranged from +3.21 ml/s to +9.5 ml/s. When compared to TURP, PAE was associated with a significantly lower IPSS reduction 1 and 3 months after the procedure. A trend toward similar symptoms improvement was however reported without statistical significance from 6 to 24 months. Major complications were rare with one bladder partial necrosis due to non-selective embolization. Mild adverse events occurred in 10 % of the patients and included transient hyperthermia, hematuria, rectal bleeding, painful urination or acute urinary retention. Further comparative studies are mandatory to assess post-operative rates of complications, especially acute urinary retention, after PAE and standard procedures.
CONCLUSION
Early reports suggest that PAE may be a promising procedure for the treatment of patients with LUTS due to BPO. However, the low level of evidence and short follow-up of published reports preclude any firm conclusion on its mid-term efficiency. Further clinical trials are warranted before any use in clinical practice.
Topics: Arteries; Embolization, Therapeutic; Humans; Lower Urinary Tract Symptoms; Male; Prostate; Prostatic Hyperplasia; Time Factors; Treatment Outcome
PubMed: 26276151
DOI: 10.1007/s00345-015-1665-6 -
European Urology Focus Mar 2021Genital reconstructive surgery (GRS) is a necessary part of transitioning for many transwomen, and there is evidence of positive effects on a person's well-being and... (Review)
Review
Genital Reconstructive Surgery in Male to Female Transgender Patients: A Systematic Review of Primary Surgical Techniques, Complication Profiles, and Functional Outcomes from 1950 to Present Day.
CONTEXT
Genital reconstructive surgery (GRS) is a necessary part of transitioning for many transwomen, and there is evidence of positive effects on a person's well-being and sexual function. Surgical techniques have evolved, from pursuing aesthetic outcome to now functional outcome with natal females as the standard.
OBJECTIVE
To systematically review the evidence, identifying the surgical techniques used in primary GRS, their complications, functional outcomes, and the tools used to assess them.
EVIDENCE ACQUISITION
The clinical question was designed using the standard PICOS format. The search complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 statement and was performed by two independent reviewers.
EVIDENCE SYNTHESIS
Europe, USA, and Thailand favour the penoscrotal technique for vaginoplasty, whereas in the UK, the penile inversion (PI) technique predominates. Primary vaginoplasty using a segment of bowel is less common, and all three techniques have comparable rates of intraoperative rectal injury. The incidence of rectovaginal fistula is reportedly higher in the PI technique. Wound haematoma and vaginal prolapse rates are comparable. Higher rates of clitoral necrosis, urethral meatal stenosis, and wound infection are reported in PI. However, the ability to orgasm, ability to have penetrative sexual intercourse, and satisfaction with aesthetic result are better with PI.
CONCLUSIONS
The evidence for GRS complications and functional outcomes is of low level. Standardised nomenclature reporting of adverse events and robust patient-reported outcome measures (PROMs) are lacking. PROMs are a powerful assessment tool, and standardised definitions of adverse events and functional outcomes should be a priority of future research.
PATIENT SUMMARY
We looked at all studies published on genital reconstructive surgery from 1950 to the present day. We assessed each surgical technique and their associated complication rates, sexual and urinary function outcomes, and how they were reported. We found the evidence to be low and weak. We suggest more robust ways of reporting complications, and the impact on patients' quality of life should be investigated.
Topics: Europe; Female; Genitalia; Genitalia, Female; Genitalia, Male; Humans; Male; Quality of Life; Plastic Surgery Procedures; Transgender Persons
PubMed: 32061539
DOI: 10.1016/j.euf.2020.01.004