CA : A Cancer Journal for Clinicians

Background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn's disease but not ulcerative colitis. Methods Two randomized, double-blind, placebo-controlled studies — the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) — evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. Results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0...

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Infliximab for induction and maintenance therapy for ulcerative colitis.

We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 pa tients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a de crease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Results Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P 1), as compared with 15.9% of pa tients who switched to placebo (adjusted difference, 26.1 percentage points for vedoliz umab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. Conclusions Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.)

https://www.nejm.org/doi/suppl/10.1056/NEJMoa1900750/suppl_file/nejmoa1900750_appendix.pdf

Vedolizumab as induction and maintenance therapy for ulcerative colitis.

Background For many years it has been claimed that observational studies find stronger treatment effects than randomized, controlled trials We compared the results of observational studies with those of randomized, controlled trials Methods We searched the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition We then searched the Medline and Cochrane data bases to identify all the randomized, controlled trials and observational studies comparing the same treatments for these conditions For each treatment, the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis-of-variance procedure and then compared with the combined magnitude of the effects in the randomized, controlled trials that evaluated the same treatment Results There were 136 reports about 19 diverse treatments, such as calcium-channel-blocker therapy for coronary artery disease, appendectomy, and interventions for subfertility In most cases, the estimates of the treatment effects from observational studies and randomized, controlled trials were similar In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the randomized, controlled trials Conclusions We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in randomized, controlled trials

https://www.nejm.org/doi/pdf/10.1056/NEJM200006223422506

A comparison of observational studies and randomized, controlled trials.

http://www.klinikcity.ru/wp-content/uploads/2012/03/Guidelines/Gastroenterology/Ulceral_Colitis_ACG_2010.pdf

Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee.

We assessed oral 5-aminosalicylic acid (5-ASA) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind, placebo-controlled trial. Patients were randomly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks. The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians' assessments at three-week intervals and by patients' recordings of daily symptoms. Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo (P less than 0.0001, rank-sum test). At a dosage of 1.6 g per day, the response was twice as good as with placebo, but the difference did not reach statistical significance (P = 0.51). Age, sex, duration of disease, duration of active symptoms, or extent of disease did not affect the clinical outcome. We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.

Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.

Percutaneous endoscopic gastrostomy. Indications, success, complications, and mortality in 314 consecutive patients.

The aim of this study was to determine the indications, success rate, procedure-related mortality, and major and minor complication rates in 314 consecutive patients in whom we attempted a percutaneous endoscopic gastrostomy. The most common indications for placement of the gastrostomy tube were neurologic (n = 235, 75%) and oropharyngeal disorders (n = 42, 13%). We noted that the gastrostomy tube was successfully placed in 299 (95%) of the 314 patients. Ninety-three percent (n = 291) of the patients had the procedure performed in the hospital and 7% (n = 23) were outpatients when the procedure was performed. In those patients with stable underlying conditions, the procedure can safely be performed in the outpatient setting. A low rate of procedure-related mortality [I%), major complication (3%), and minor complication (13%) was noted. Our experience suggests that the percutaneous endoscopic gastrostomy is safe and has a low mortality rate even in patients who are medically debilitated secondary to their underlying disease.

https://www.gastrojournal.org/article/0016-5085(87)90312-X/pdf

Indications, Success, Complications, and Mortality in 314 Consecutive Patients

Small-bowel imaging in Crohn's disease: a prospective, blinded, 4-way comparison trial

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.

Kenneth W. Schroeder

Papers

Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study.

Percutaneous endoscopic gastrostomy. Indications, success, complications, and mortality in 314 consecutive patients.

Indications, Success, Complications, and Mortality in 314 Consecutive Patients

Small-bowel imaging in Crohn's disease: a prospective, blinded, 4-way comparison trial

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy. A prospective, randomized, double-blind clinical trial