Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
<b>BACKGROUND: </b>The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.<b>METHODS: </b>We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components).<b>RESULTS: </b>The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.<b>CONCLUSIONS: </b>Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).
Background: The objective was to evaluate the efficacy and safety of ustekinumab (UST) through Week 16 induction among patients with moderate‐severe UC randomised to UST in the UNIFI Phase 3 clinical trial. Week 8 induction data have been previously reported.1 Methods: Rates of overall clinical response and clinical remission among blinded patients randomised to IV UST induction were used to evaluate efficacy through Week 16. The number of patients who achieved each endpoint included patients who achieved the endpoint at Week 8 after initial IV UST induction and patients who achieved the same endpoint at Week 16 following a blinded dose of UST 90 mg SC at Week 8 if they were not in clinical response at Week 8. Results: Among patients randomised to UST at Week 0, 77.6% achieved clinical response within 16 weeks: 56.5% at Week 8 after IV induction and an additional 21.1% at Week 16 after receiving UST SC at Week 8. Among the Week 8 non‐responders to UST IV induction who received UST SC at Week 8, 57.9% achieved clinical response at Week 16. Among patients randomised to UST at Week 0, 18.8% achieved clinical remission within 16 weeks: 15.6% at Week 8 after IV induction and an additional 3.2% at Week 16 after receiving an additional UST dose at Week 8. Among the Week 8 non‐responders to UST IV induction who received UST SC at Week 8, 9.4% achieved clinical remission at Week 16. The proportions of patients who achieved clinical response within 16 weeks was lower for patients with a history of biological failure compared with nonbiological failure patients: 70.6% vs. 84.9% (Table 1). Similarly, the proportions of patients who achieved clinical remission during induction within 16 weeks were lower for biological failure patients compared with non‐biological failure patients: 13.3% vs. 24.7% (Table 2). The AE profile for patients who received a single UST IV dose and those with an additional UST dose SC at Week 8 were similar and consistent with the AE profile for patients that received PBO. Conclusions: UST is safe and effective induction therapy in patients with moderate‐severe UC. Similar to results from the Crohn's disease programme, these data support a clinical rationale for continuing treatment with UST through at least one SC dose 8 weeks after IV induction in patients with moderate‐severe UC. (Table Presented).
Patients with inflammatory bowel disease (IBD) have differences in their gastrointestinal microbiome compared with healthy individuals, although it is unclear whether this is a cause or consequence of chronic inflammation. There is hope that manipulation of the gut microbiome through fecal microbiota transplant (FMT), commonly used to treat patients with Clostridium difficile infection, may also be an effective therapy in IBD. This article reviews the evidence supporting FMT in IBD, including case reports, case series, and randomized controlled trials. The article also focuses on questions of safety and speculates on the future of this therapy.
<b>BACKGROUND: </b>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.<b>METHODS: </b>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.<b>RESULTS: </b>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.<b>CONCLUSIONS: </b>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.).
The purpose of this study is to evaluate the efficacy and safety of vedolizumab intravenous (IV) treatment compared to adalimumab subcutaneous (SC) treatment over a 52-week treatment period.
The purpose of this study is to evaluate the efficacy and safety of ustekinumab as intravenous (IV: into the vein) infusion in induction study in participants with moderately to severely active Ulcerative Colitis (UC) and as subcutaneous (SC) administration in maintenance study in participants with moderately to severely active Ulcerative Colitis (UC) who have demonstrated a clinical response to Induction treatment with IV ustekinumab.
BACKGROUND e OBIETTIVI: golimumab sottocutaneo, un anticorpo monoclonale interamente umano fattore di necrosi tumorale-α (TNF), è stato valutato come terapia di mantenimento in TNFa antagonisti adulti naive con terapia convenzionale da moderata a grave colite ulcerosa attiva, nonostante, che ha risposto a terapia di induzione golimumab.
METODI: Abbiamo eseguito una fase 3, in doppio cieco di pazienti che hanno completato gli studi di induzione golimumab (Programma di colite ulcerosa Studi di ricerca Utilizzando un trattamento sperimentale, ad esempio, PURSUIT). I pazienti che hanno risposto alla terapia di induzione con golimumab (n = 464) sono stati assegnati in modo casuale a gruppi trattati con placebo o iniezioni di 50 o 100 mg golimumab ogni 4 settimane fino alla settimana 52. I pazienti che hanno risposto al placebo nello studio di induzione hanno continuato a ricevere placebo. Responder nello studio di induzione hanno ricevuto 100 mg di golimumab. L'end point primario era la risposta clinica mantenuta fino alla settimana 54; endpoint secondari includevano la remissione clinica e la guarigione della mucosa in entrambe le settimane 30 e 54.
RISULTATI: La risposta clinica è stata mantenuta fino alla settimana 54 in 47,0% dei pazienti trattati con 50 mg di golimumab, il 49,7% dei pazienti trattati con golimumab 100 mg, e il 31,2% dei pazienti trattati con placebo (p = 0,010 e P <.001, rispettivamente). Alle settimane 30 e 54, una più alta percentuale di pazienti che hanno ricevuto golimumab 100 mg erano in remissione clinica e aveva guarigione della mucosa (27,8% e 42,4%) rispetto ai pazienti trattati con placebo (15,6% e 26,6%; P = 0,004 e P =. 002, rispettivamente) o 50 mg di golimumab (23,2% e 41,7%, rispettivamente). Percentuali di gravi eventi avversi sono stati del 7,7%, 8,4%, e del 14,3% tra i pazienti trattati con placebo, 50 mg o 100 mg di golimumab, rispettivamente; percentuali di infezioni gravi è risultato dell'1,9%, 3,2%, e del 3,2% rispettivamente. Tra tutti i pazienti indicati golimumab in studio, 3 morti (da sepsi, tubercolosi, e insufficienza cardiaca, il tutto in pazienti che hanno ricevuto golimumab 100 mg) e 4 sviluppato tubercolosi attiva.
CONCLUSIONI: golimumab (50 mg o 100 mg) mantenuto la risposta clinica fino alla settimana 54 nei pazienti che hanno risposto alla terapia di induzione con golimumab e aveva da moderata a grave colite ulcerosa attiva; pazienti che hanno ricevuto 100 mg di golimumab had remissione clinica e la guarigione della mucosa alle settimane 30 e 54. Sicurezza era coerente con quello riportato per altri antagonisti TNF-alfa e di golimumab in altre indicazioni approvate. Numero ClinicalTrials.gov: NCT00488631.
BACKGROUND e OBIETTIVI: Poco si sa circa l'efficacia di golimumab, un anticorpo monoclonale interamente umano per il fattore di necrosi tumorale (TNF) -α, per il trattamento della colite ulcerosa (UC). Abbiamo valutato la terapia di induzione golimumab per via sottocutanea nei pazienti naïve antagonisti TNF-α con moderata-grave UC nonostante il trattamento convenzionale.
METODI: Abbiamo integrato fase 2 dose inchiesta e di fase 3 dose conferma studi in doppio cieco in uno studio di 1.064 adulti con UC (punteggio Mayo: 6-12; subscore endoscopico ≥ 2; 774 pazienti in fase 3). I pazienti sono stati assegnati in modo casuale a gruppi somministrate dosi di golimumab 100 mg e poi 50 mg (solo fase 2), 200 mg e poi 100 mg, o 400 mg e poi 200 mg, 2 settimane l'una dall'altra. L'end point primario era la settimana di fase 3-6 risposta clinica. Gli endpoint secondari comprendevano la settimana-6 remissione clinica, la guarigione della mucosa, e Inflammatory Bowel Disease Questionnaire (IBDQ) variazione del punteggio.
RISULTATI: Nella fase 2, i cambiamenti mediani rispetto al basale del punteggio Mayo were -1.0, -3.0, -2.0, e -3.0, nei gruppi trattati con placebo, 100 mg / 50 mg, 200/100 mg, e 400/200 mg golimumab, rispettivamente. Nella fase 3, i tassi di risposta clinica alla settimana 6 erano 51,0% e il 54,9% tra i pazienti trattati con 200 mg / 100 mg e 400 mg / 200 mg golimumab, rispettivamente, contro il 30,3% tra quelli trattati con placebo (entrambi, P ≤ 0001) . Tassi di remissione clinica e la guarigione della mucosa e significare cambiamenti nei punteggi IBDQ erano significativamente maggiore in entrambi i gruppi golimumab contro il gruppo placebo (P ≤ 0,0014, tutti i confronti). I tassi di eventi avversi gravi sono 6,1% e il 3,0%, e tassi di infezione grave è stata dell'1,8% e dello 0,5%, nel gruppo placebo e golimumab, rispettivamente. Un paziente in 400 mg / 200 mg gruppo morto a causa di complicanze chirurgiche di un ascesso ischiorettale.
In conclusione, il trattamento con golimumab per via sottocutanea induce risposta clinica, remissione e guarigione della mucosa, e aumenta la qualità della vita in una maggiore percentuale di pazienti con UC attivo rispetto al placebo. Numero ClinicalTrials.gov: NCT00487539.
Ulcerative colitis (UC) is an idiopathic inflammatory disorder. These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the evidence was not appropriate for GRADE, but there was consensus of significant clinical merit, "key concept" statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not only, approach to clinical scenarios.
