Abstract
Background & Aims Resistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis. This was a randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis. Methods Eleven patients received rectal tacrolimus (0.5 mg/mL), and 10 placebo, for 8 weeks. The primary endpoint was clinical response by using the Mayo Clinic score. Results A planned interim analysis after 20 patients had completed the study demonstrated highly significant differences between the groups and the study was closed because of ethical considerations with patients already recruited allowed to complete the study. The primary endpoint was met in 8 of 11 patients receiving rectal tacrolimus and 1 of 10 patients receiving placebo (73% vs 10%; P = .004). Of the secondary endpoints, 5 patients with rectal tacrolimus achieved clinical remission compared with none receiving placebo (45% vs 0%; P = .015). Mucosal healing at Week 8 was achieved in 8 patients receiving rectal tacrolimus compared with 1 (73% vs 10%) receiving placebo (P = .004). The Inflammatory Bowel Disease Questionnaire increased ≥16 points over baseline in 5 of the tacrolimus and 2 (45% vs 20%) of the placebo patients (P = .36). Finally, the average partial Mayo score was numerically lower in the tacrolimus-treated group compared with placebo at Week 2 (4.3 ± 0.74 vs 5.8 ± 0.64; P = .15) and Week 4 (3.7 ± 0.96 vs 5.8 ± 0.6; P = .08) but was significantly lower at Week 8 (3.3 ± 1.2 vs 6.7 ± 0.62; P = .01). There were no safety issues identified with rectal tacrolimus use. Conclusions Rectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission, and mucosal healing in resistant ulcerative proctitis (Clinicaltrials.gov registration: NCT01418131).
| Original language | English |
|---|---|
| Pages (from-to) | 1248-1255 |
| Number of pages | 8 |
| Journal | Clinical Gastroenterology and Hepatology |
| Volume | 15 |
| Issue number | 8 |
| Early online date | 7 Mar 2017 |
| DOIs | |
| Publication status | Published - 1 Aug 2017 |
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Efficacy of rectal tacrolimus for induction therapy in patients with resistant ulcerative proctitis. / Lawrance, Ian C.; Baird, Angela; Lightowler, Daniel; Radford-Smith, Graham; Andrews, Jane M.; Connor, Susan.
In: Clinical Gastroenterology and Hepatology, Vol. 15, No. 8, 01.08.2017, p. 1248-1255.Research output: Contribution to journal › Article
TY - JOUR
T1 - Efficacy of rectal tacrolimus for induction therapy in patients with resistant ulcerative proctitis
AU - Lawrance, Ian C.
AU - Baird, Angela
AU - Lightowler, Daniel
AU - Radford-Smith, Graham
AU - Andrews, Jane M.
AU - Connor, Susan
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Background & Aims Resistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis. This was a randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis. Methods Eleven patients received rectal tacrolimus (0.5 mg/mL), and 10 placebo, for 8 weeks. The primary endpoint was clinical response by using the Mayo Clinic score. Results A planned interim analysis after 20 patients had completed the study demonstrated highly significant differences between the groups and the study was closed because of ethical considerations with patients already recruited allowed to complete the study. The primary endpoint was met in 8 of 11 patients receiving rectal tacrolimus and 1 of 10 patients receiving placebo (73% vs 10%; P = .004). Of the secondary endpoints, 5 patients with rectal tacrolimus achieved clinical remission compared with none receiving placebo (45% vs 0%; P = .015). Mucosal healing at Week 8 was achieved in 8 patients receiving rectal tacrolimus compared with 1 (73% vs 10%) receiving placebo (P = .004). The Inflammatory Bowel Disease Questionnaire increased ≥16 points over baseline in 5 of the tacrolimus and 2 (45% vs 20%) of the placebo patients (P = .36). Finally, the average partial Mayo score was numerically lower in the tacrolimus-treated group compared with placebo at Week 2 (4.3 ± 0.74 vs 5.8 ± 0.64; P = .15) and Week 4 (3.7 ± 0.96 vs 5.8 ± 0.6; P = .08) but was significantly lower at Week 8 (3.3 ± 1.2 vs 6.7 ± 0.62; P = .01). There were no safety issues identified with rectal tacrolimus use. Conclusions Rectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission, and mucosal healing in resistant ulcerative proctitis (Clinicaltrials.gov registration: NCT01418131).
AB - Background & Aims Resistant ulcerative proctitis can be extremely difficult to manage. Topically administered tacrolimus, however, may be effective in difficult-to-treat proctitis. This was a randomized, double-blind, placebo-controlled induction trial of rectal tacrolimus in patients with active ulcerative colitis. Methods Eleven patients received rectal tacrolimus (0.5 mg/mL), and 10 placebo, for 8 weeks. The primary endpoint was clinical response by using the Mayo Clinic score. Results A planned interim analysis after 20 patients had completed the study demonstrated highly significant differences between the groups and the study was closed because of ethical considerations with patients already recruited allowed to complete the study. The primary endpoint was met in 8 of 11 patients receiving rectal tacrolimus and 1 of 10 patients receiving placebo (73% vs 10%; P = .004). Of the secondary endpoints, 5 patients with rectal tacrolimus achieved clinical remission compared with none receiving placebo (45% vs 0%; P = .015). Mucosal healing at Week 8 was achieved in 8 patients receiving rectal tacrolimus compared with 1 (73% vs 10%) receiving placebo (P = .004). The Inflammatory Bowel Disease Questionnaire increased ≥16 points over baseline in 5 of the tacrolimus and 2 (45% vs 20%) of the placebo patients (P = .36). Finally, the average partial Mayo score was numerically lower in the tacrolimus-treated group compared with placebo at Week 2 (4.3 ± 0.74 vs 5.8 ± 0.64; P = .15) and Week 4 (3.7 ± 0.96 vs 5.8 ± 0.6; P = .08) but was significantly lower at Week 8 (3.3 ± 1.2 vs 6.7 ± 0.62; P = .01). There were no safety issues identified with rectal tacrolimus use. Conclusions Rectal tacrolimus was more effective than placebo for induction of a clinical response, clinical remission, and mucosal healing in resistant ulcerative proctitis (Clinicaltrials.gov registration: NCT01418131).
KW - Blinded Randomized Clinical Trial
KW - Proctitis
KW - Tacrolimus
KW - Ulcerative Colitis
UR - http://www.scopus.com/inward/record.url?scp=85019617063&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2017.02.027
DO - 10.1016/j.cgh.2017.02.027
M3 - Article
VL - 15
SP - 1248
EP - 1255
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
SN - 1542-3565
IS - 8
ER -