Estudios primarios incluidos en esta revisión sistemática

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Estudio primario

No clasificado

Prospective cohort study of appendicectomy for treatment of therapy-refractory ulcerative colitis.

Revista The British journal of surgery
Año 2019
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INTRODUCTION: Appendicectomy may reduce relapses and need for medication in patients with ulcerative colitis, but long-term prospective data are lacking. This study aimed to analyse the effect of appendicectomy in patients with refractory ulcerative colitis. METHODS: In this prospective multicentre cohort series, all consecutive patients with refractory ulcerative colitis referred for proctocolectomy between November 2012 and June 2015 were counselled to undergo laparoscopic appendicectomy instead. The primary endpoint was clinical response (reduction of at least 3 points in the partial Mayo score) at 12 months and long-term follow-up. Secondary endpoints included endoscopic remission (endoscopic Mayo score of 1 or less), failure (colectomy or start of experimental medication), and changes in Inflammatory Bowel Disease Questionnaire (IBDQ) (range 32-224), EQ-5D™ and EORTC-QLQ-C30-QL scores. RESULTS: A total of 28 patients (13 women; median age 40·5 years) underwent appendicectomy. The mean baseline IBDQ score was 127·0, the EQ-5D™ score was 0·65, and the EORTC-QLQ-C30-QL score was 41·1. At 12 months, 13 patients had a clinical response, five were in endoscopic remission, and nine required a colectomy (6 patients) or started new experimental medical therapy (3). IBDQ, EQ-5D™ and EORTC-QLQ-C30-QL scores improved to 167·1 (P < 0·001), 0·80 (P = 0·003) and 61·0 (P < 0·001) respectively. After a median of 3·7 (range 2·3-5·2) years, a further four patients required a colectomy (2) or new experimental medical therapy (2). Thirteen patients had a clinical response and seven were in endoscopic remission. The improvement in IBDQ, EQ-5D™ and the EORTC-QLQ-C30-QL scores remained stable over time. CONCLUSION: Appendicectomy resulted in a clinical response in nearly half of patients with refractory ulcerative colitis and a substantial proportion were in endoscopic remission. Elective appendicectomy should be considered before proctocolectomy in patients with therapy-refractory ulcerative colitis.

Estudio primario

No clasificado

Tofacitinib in Patients with Ulcerative Colitis: health-Related Quality of Life in Phase 3 Randomised Controlled Induction and Maintenance Studies

Revista Journal of Crohn's & colitis
Año 2018
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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Background and Aims: Tofacitinib is an oral, small molecule Janus kinase [JAK] inhibitor that is being investigated for ulcerative colitis [UC]. We evaluated health‐related quality of life [HRQoL] in tofacitinib UC Phase 3 studies. Methods: Patients ≥ 18 years old in OCTAVE Induction 1 [N = 598] and 2 [N = 541] with moderately to severely active UC were randomised [1:4] to placebo or tofacitinib 10 mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re‐randomised [1:1:1] clinical responders [N = 593] from induction studies to placebo, tofacitinib 5 mg BID, or 10 mg BID, for 52 weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and SF‐36v2® Health Survey [SF‐36v2] assessed HRQoL. Results: In OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were greater with tofacitinib 10 mg BID at Week 8 [28.9 and 31.5] versus placebo [15.4 and 17.2; p < 0.0001]; mean changes from baseline SF‐36v2 Physical and Mental Component Summaries [PCS/MCS] were also greater with 10 mg BID [PCS: 6.8 and 6.8; MCS: 6.8 and 7.6] versus placebo [PCS: 2.5 and 4.6; MCS: 3.5 and 4.4; p < 0.01]. In OCTAVE Sustain atWeek 52, changes in IBDQ were maintained with tofacitinib 5 mg [‐1.3] and 10 mg BID [0.6], and larger with placebo [‐20.2; p < 0.0001]. Changes in SF‐36v2 PCS/MCS were also maintained with 5 mg [PCS: 0.0; MCS: ‐1.0] and 10 mg BID [PCS: 0.3; MCS: 0.1] versus placebo [PCS: ‐5.2; MCS: ‐6.7; p < 0.0001] at Week 52 in OCTAVE Sustain. Conclusions: Tofacitinib 10 mg BID induction therapy significantly improved HRQoL versus placebo at Week 8. Improvements were maintained through 52 weeks' maintenance therapy with tofacitinib 5 mg and 10 mg BID. ClinicalTrials.gov registration numbers: NCT01465763, NCT01458951 and NCT01458574.

Estudio primario

No clasificado

Peficitinib, an Oral Janus Kinase Inhibitor, in Moderate-to-severe Ulcerative Colitis: Results From a Randomised, Phase 2 Study.

Revista Journal of Crohn's & colitis
Año 2018
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Este artículo está incluido en 3 Revisiones sistemáticas Revisiones sistemáticas (3 referencias)

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BACKGROUND AND AIMS: Janus kinase [JAK] inhibitors have shown efficacy in ulcerative colitis [UC]. We studied the dose-response, efficacy, and safety of peficitinib, an oral JAK inhibitor, in patients with moderate-to-severe UC. METHODS: In this Phase 2b, dose-ranging trial, we evaluated peficitinib at 25 mg once daily [o.d.], 75 mg o.d., 150 mg o.d., and 75 mg twice daily versus placebo for efficacy and safety in 219 patients with moderate-to-severe UC. The primary outcome was peficitinib dose-response at Week 8, with response assessed using Mayo score change from baseline. Secondary endpoints were clinical response, clinical remission, mucosal healing, change from baseline in Inflammatory Bowel Disease Questionnaire [IBDQ], and normalisation of inflammatory biomarkers at Week 8; other secondary endpoints were treatment response through Week 16 and through Week 32 for patients in clinical response at Week 8. Safety was assessed through Week 36 or 4 weeks after the last dose. RESULTS: A statistically significant peficitinib dose-response was not demonstrated at Week 8, although a numerically greater proportion of patients receiving peficitinib ≥75 mg o.d. achieved clinical response, remission, and mucosal healing at Week 8, supported by IBDQ improvement and inflammatory biomarker normalisation. Treatment-emergent adverse event [TEAE] rates reported through Week 8 and the final safety visit were higher in the combined peficitinib group than in the placebo group; patients receiving doses of ≥75 mg o.d. peficitinib reported TEAEs more frequently. CONCLUSIONS: No dose-response in patients with moderate-to-severe UC was demonstrated with peficitinib, but evidence of efficacy was suggested at doses ≥75 mg o.d. The safety profile of peficitinib was consistent with current information. ClinicalTrials.gov NCT01959282.

Estudio primario

No clasificado

Effects of vedolizumab on health-related quality of life in patients with ulcerative colitis: results from the randomised GEMINI 1 trial

Revista Alimentary pharmacology & therapeutics
Año 2017
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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BACKGROUND: Health‐related quality of life (HRQL) is often diminished in patients with ulcerative colitis. AIM: To evaluate the effects of vedolizumab on HRQL in patients with ulcerative colitis. METHODS: Using maintenance phase data from the GEMINI 1 study, an analysis of covariance model was used to calculate mean differences between the vedolizumab and placebo groups in changes from baseline to week 52 for 3 HRQL instruments: The Inflammatory Bowel Disease Questionnaire (IBDQ), 36‐Item Short Form Health Survey (SF‐36), and EQ‐5D. Proportions of patients meeting minimal clinically important difference (MCID) thresholds for changes on these instruments were compared between treatment groups for the overall population and for clinically important subgroups. Concordance between clinical remission and remission defined using IBDQ scores was examined. RESULTS: Compared with placebo‐treated patients, vedolizumab‐treated patients had greater improvements (152‐201%) in IBDQ, EQ‐5D visual analogue scale (VAS), and EQ‐5D utility scores. Greater proportions (6.9‐19.9%) of vedolizumab‐treated patients than placebo‐treated patients met MCID thresholds for all the instruments. Vedolizumab‐treated patients with lower baseline disease activity and those without prior tumour necrosis factor (TNF) antagonist failure had greater HRQL improvements. Among 127 patients with clinical remission based on complete Mayo Clinic scores, >80% also had IBDQ remission; >70% of the 150 patients with IBDQ remission demonstrated clinical remission. CONCLUSIONS: Vedolizumab therapy was associated with significant improvements in HRQL measures compared with placebo. Benefits were greater in patients with lower disease activity and no prior TNF antagonist failure.

Estudio primario

No clasificado

Efficacy and safety of golimumab 52-week maintenance therapy in Japanese patients with moderate to severely active ulcerative colitis: a phase 3, double-blind, randomized, placebo-controlled study-(PURSUIT-J study).

Autores Hibi T , Imai Y , Senoo A , Ohta K , Ukyo Y
Revista Journal of gastroenterology
Año 2017
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 6 Revisiones sistemáticas Revisiones sistemáticas (6 referencias)

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BACKGROUND: The global phase 3 studies of golimumab [PURSUIT-SC and PURSUIT-maintenance (M)], an anti-tumor necrosis factor-α (anti-TNFα) antibody, have demonstrated clinical efficacy and safety as induction and maintenance therapies in patients with moderate to severely active ulcerative colitis (UC). This study aimed to evaluate the efficacy and safety of golimumab as maintenance therapy in the Japanese population. METHODS: In this phase 3, double-blind (DB), placebo-controlled, parallel group, randomized withdrawal study, 144 Japanese patients with moderately to severely active UC received golimumab doses of 200 mg (at week 0) and 100 mg (at week 2) subcutaneously during the 6-week open-label induction phase. Patients who responded to golimumab induction therapy entered the DB maintenance (M) phase and were randomized (1:1) to receive 100 mg of golimumab subcutaneous injection (SC) or placebo every 4 weeks for 52 weeks. The primary endpoint was clinical response through M-week 54; secondary endpoints included clinical remission and mucosal healing at M-week 30 and 54. RESULTS: Among induction responders, more patients on golimumab treatment (56.3%) maintained clinical response through M-week 54 versus the placebo group (19.4%). At both M-week 30 and 54, 50% golimumab-treated patients achieved clinical remission versus the placebo group (6.5%) and a higher proportion of patients on golimumab (59.4%) experienced mucosal healing than the placebo group (16.1%). Incidence of treatment-emergent adverse events was 96.9% in the golimumab group and 71% in the placebo group. Overall, the efficacy and safety results in this study were comparable with those observed in global studies. CONCLUSIONS: Golimumab SC treatment maintained clinical efficacy through week 54 among induction responders, and no new safety signals were observed in the patients with moderate to severely active UC. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov NCT01863771.

Estudio primario

No clasificado

Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis.

Revista The New England journal of medicine
Año 2017
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Este artículo está incluido en 12 Revisiones sistemáticas Revisiones sistemáticas (12 referencias)

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BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. We further evaluated the efficacy of tofacitinib as induction and maintenance therapy. METHODS: We conducted three phase 3, randomized, double-blind, placebo-controlled trials of tofacitinib therapy in adults with ulcerative colitis. In the OCTAVE Induction 1 and 2 trials, 598 and 541 patients, respectively, who had moderately to severely active ulcerative colitis despite previous conventional therapy or therapy with a tumor necrosis factor antagonist were randomly assigned to receive induction therapy with tofacitinib (10 mg twice daily) or placebo for 8 weeks. The primary end point was remission at 8 weeks. In the OCTAVE Sustain trial, 593 patients who had a clinical response to induction therapy were randomly assigned to receive maintenance therapy with tofacitinib (either 5 mg or 10 mg twice daily) or placebo for 52 weeks. The primary end point was remission at 52 weeks. RESULTS: In the OCTAVE Induction 1 trial, remission at 8 weeks occurred in 18.5% of the patients in the tofacitinib group versus 8.2% in the placebo group (P=0.007); in the OCTAVE Induction 2 trial, remission occurred in 16.6% versus 3.6% (P<0.001). In the OCTAVE Sustain trial, remission at 52 weeks occurred in 34.3% of the patients in the 5-mg tofacitinib group and 40.6% in the 10-mg tofacitinib group versus 11.1% in the placebo group (P<0.001 for both comparisons with placebo). In the OCTAVE Induction 1 and 2 trials, the rates of overall infection and serious infection were higher with tofacitinib than with placebo. In the OCTAVE Sustain trial, the rate of serious infection was similar across the three treatment groups, and the rates of overall infection and herpes zoster infection were higher with tofacitinib than with placebo. Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels. CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo. (Funded by Pfizer; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain ClinicalTrials.gov numbers, NCT01465763 , NCT01458951 , and NCT01458574 , respectively.).

Estudio primario

No clasificado

Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial.

Revista Lancet (London, England)
Año 2017
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Este artículo está incluido en 17 Revisiones sistemáticas Revisiones sistemáticas (17 referencias)

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BACKGROUND: The intestinal microbiota is implicated in the pathogenesis of ulcerative colitis. Faecal microbiota transplantation is a novel form of therapeutic microbial manipulation, but its efficacy in ulcerative colitis is uncertain. We aimed to establish the efficacy of intensive-dosing, multidonor, faecal microbiota transplantation in active ulcerative colitis. METHODS: We conducted a multicentre, double-blind, randomised, placebo-controlled trial at three hospitals in Australia. We randomly allocated patients with active ulcerative colitis (Mayo score 4-10) in a 1:1 ratio, using a pre-established randomisation list, to either faecal microbiota transplantation or placebo colonoscopic infusion, followed by enemas 5 days per week for 8 weeks. Patients, treating clinicians, and other study staff were unaware of the assigned treatment. Faecal microbiota transplantation enemas were each derived from between three and seven unrelated donors. The primary outcome was steroid-free clinical remission with endoscopic remission or response (Mayo score ≤2, all subscores ≤1, and ≥1 point reduction in endoscopy subscore) at week 8. Analysis was by modified intention-to-treat and included all patients receiving one study dose. We performed 16S rRNA stool analysis to assess associated microbial changes. This trial is registered with ClinicalTrials.gov, number NCT01896635. The trial has ended; this report presents the final analysis. FINDINGS: From November, 2013, to May, 2015, 85 patients were enrolled to our trial, of whom 42 were randomly assigned faecal microbiota transplantation and 43 were allocated placebo. One patient assigned faecal microbiota transplantation and three allocated placebo did not receive study treatment and were excluded from the analysis. The primary outcome was achieved in 11 (27%) of 41 patients allocated faecal microbiota transplantation versus three (8%) of 40 who were assigned placebo (risk ratio 3·6, 95% CI 1·1-11·9; p=0·021). Adverse events were reported by 32 (78%) of 41 patients allocated faecal microbiota transplantation and 33 (83%) of 40 who were assigned placebo; most were self-limiting gastrointestinal complaints, with no significant difference in number or type of adverse events between treatment groups. Serious adverse events occurred in two patients assigned faecal microbiota transplantation and in one allocated placebo. Microbial diversity increased with and persisted after faecal microbiota transplantation. Several bacterial taxa were associated with clinical outcome; in particular, the presence of Fusobacterium spp was associated with lack of remission. INTERPRETATION: Intensive-dosing, multidonor, faecal microbiota transplantation induces clinical remission and endoscopic improvement in active ulcerative colitis and is associated with distinct microbial changes that relate to outcome. Faecal microbiota transplantation is, thus, a promising new therapeutic option for ulcerative colitis. Future work should focus on precisely defining the optimum treatment intensity and the role of donor-recipient matching based on microbial profiles. FUNDING: Broad Medical Research Program, Gastroenterological Society of Australia, Mount Sinai (New York) SUCCESS fund, University of New South Wales.

Estudio primario

No clasificado

Fecal microbiota transplantation improves the quality of life in patients with inflammatory bowel disease

Autores Wei Y , Zhu W , Gong J , Guo D , Gu L , Li N , Li J
Revista Gastroenterology research and practice
Año 2015
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 7 Revisiones sistemáticas Revisiones sistemáticas (7 referencias)

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Introduction. To determine the effect of fecal microbiota transplantation (FMT) on quality of life (QoL) in patients with inflammatory bowel disease (IBD). Methods. Fourteen IBD patients, including 11 Ulcerative colitis (UC) and 3 Crohn's disease (CD), were treated with FMT via colonoscopy or nasojejunal tube infusion. QoL was measured by IBD Questionnaire (IBDQ). Disease activity and IBDQ were evaluated at enrollment and four weeks after treatment. Patients' attitude concerning the treatment was also investigated. Results. One patient was excluded due to intolerance. All the other patients finished the study well. Mean Mayo score in UC patients decreased significantly (5.80 ± 1.87 versus 1.50 ± 1.35, P < 0.01). Mean IBDQ scores of both UC and CD patients increased (135.50 ± 27.18 versus 177.30 ± 20.88, P = 0.00063, and 107.33 ± 9.45 versus 149.00 ± 20.07, P = 0.024) four weeks after fecal microbiota transplantation. There was no correlation between the IBDQ score and Mayo score before and after FMT. Patients refused to take FMT as treatment repeatedly in a short time. Conlusions. Fecal microbiota transplantation improves quality of life significantly in patients with inflammatory bowel disease.

Estudio primario

No clasificado

Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes

Revista BMC gastroenterology
Año 2015
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 1 Revisión sistemática Revisiones sistemáticas (1 referencia)

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BACKGROUND: Tofacitinib, a novel, oral Janus kinase inhibitor, demonstrated a dose‐dependent efficacy for induction of clinical response and remission in patients with active ulcerative colitis (UC). The objective of the current study was to determine the effect of tofacitinib on patient‐reported outcomes (PROs). METHODS: Eligible patients (≥18 years of age) with a diagnosis of active UC (total Mayo score of 6‐12 points and moderately‐to‐severely active disease on sigmoidoscopy) were randomized in a 2:2:2:3:3 ratio to receive oral tofacitinib 0.5 mg, 3 mg, 10 mg, or 15 mg, or placebo twice daily (BID) for 8 weeks. PROs were assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Inflammatory Bowel Disease Patient‐Reported Treatment Impact (IBD PRTI) survey. RESULTS: At Week 8, mean IBDQ total scores had improved relative to baseline across all five treatment groups (baseline range 123.2‐134.5; Week 8 range 149.6‐175.4). Improvement from baseline was significantly greater (P = 0.001) for tofacitinib 15 mg BID versus placebo. For tofacitinib 15 mg BID, most patients reported satisfaction or extreme satisfaction, definite preference for tofacitinib, and definite willingness to use tofacitinib again on the IBD PRTI at week 8. Patients achieving endoscopic remission (Mayo endoscopy score of 0) had significantly higher IBDQ scores and favorable PRTI scores than those not achieving endoscopic remission. CONCLUSIONS: Short‐term treatment with tofacitinib BID was associated with dose‐dependent improvement in health‐related quality of life and patient preferences for tofacitinib. The results complement previously reported efficacy and safety data for the Phase II study. (NCT 00787202, November 6, 2008).

Estudio primario

No clasificado

Eficacia y seguridad de adalimumab en pacientes japoneses con moderada a severamente activa de la colitis ulcerosa.

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Revista Journal of gastroenterology
Año 2014
Enlaces Pubmed DOI PubMed Central

Este artículo está incluido en 22 Revisiones sistemáticas Revisiones sistemáticas (22 referencias)

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ANTECEDENTES: El adalimumab es un anticuerpo completamente humano, monoclonal contra el factor de necrosis tumoral que está aprobado en los países occidentales para el tratamiento de moderada a severamente activa colitis ulcerosa (UC). MÉTODOS: Este 52 semanas, la fase 3.2, aleatorizado estudio doble ciego evaluó adalimumab, para la inducción y el tratamiento de mantenimiento en 273 pacientes japoneses anti-TNF-ingenuo con CU que fueron refractarios a los corticoides, inmunomoduladores, o ambos. Los pacientes recibieron placebo, adalimumab 80/40 (80 mg en la semana 0, 40 mg cada dos semanas), o adalimumab 160/80 (160/80 mg en la semana 0/2, luego 40 mg cada dos semanas), además de fondo terapia UC. RESULTADOS: En la semana 8, las tasas de remisión fueron similares entre los grupos de tratamiento, pero más pacientes tratados con adalimumab 160/80 logra respuesta (placebo, 35%; 80/40, 43%; 160/80, del 50%; p = 0,044 para el 160 / 80 vs placebo) y curación de la mucosa (placebo, 30%; 80/40, 39%; 160/80, de 44%, p = 0,045 para 160/80 frente a placebo) en comparación con placebo. En la semana 52, más pacientes tratados con adalimumab 40 mg cada dos semanas lograron respuesta (18 vs 31%, p = 0,021), la remisión (7 vs 23%, p = 0,001), y la curación de la mucosa (16 vs 29%, p = 0,015 ) en comparación con placebo. Semana 8 respuesta a adalimumab se asoció con mayores tasas de respuesta (61%), la remisión (46%), y la curación de la mucosa (57%) en la semana 52 con relación a la población general. Las tasas de eventos adversos graves fueron similares entre los grupos de tratamiento. CONCLUSIONES: La inducción con adalimumab 160/80 mg llevado a la respuesta temprana y la curación de la mucosa. Adalimumab Mantenimiento tuvo mayores tasas de respuesta a largo plazo, la remisión y la curación de la mucosa en comparación con el placebo. No se identificaron nuevas señales de seguridad.