Long-term MRI-guided combined anti-TNF-α and thiopurine therapy for Crohn's perianal fistulas.
BACKGROUND
Anti-tumor necrosis factor (TNF) therapy heals many Crohn's disease (CD) anal fistulas clinically but the rate, extent, and durability of deep tissue healing and factors influencing long-term outcome are unknown.


METHODS
Consecutive patients with CD-related perianal (anal, rectovaginal, anolabial) fistulas treated with infliximab or adalimumab were monitored prospectively both clinically and radiologically using magnetic resonance imaging (MRI).


RESULTS
Forty-one consecutive patients with CD-related perianal fistulas were treated with infliximab (n = 32) or adalimumab (n = 9; following infliximab failure) in combination with a thiopurine (unless intolerant). Fifty-eight percent of all patients, comprising 66% and 43% of infliximab and adalimumab-treated patients, respectively, demonstrated remission or response at 3 years. Thirty-three percent of infliximab treated patients maintained clinical remission at 3 years. Radiological healing lagged behind clinical remission by a median of 12 months. The likelihood of clinical remission at any time was five times greater in patients who had early clinical response within 6 weeks than those without. A higher number of fistula tracts was associated with reduced clinical remission. All patients who achieved radiological healing maintained healing on infliximab treatment, while only 43% maintained healing after cessation of anti-TNF therapy.


CONCLUSIONS
Combination anti-TNF and thiopurine therapy provides sustained benefit in patients with perianal CD fistula. Early clinical response is associated with subsequent clinical remission. Radiological healing is slower than clinical healing. Radiologically healed fistula tracts maintain healing on infliximab but can recur after cessation of therapy.
Department of Surgery, St Mark's Hospital, London, UK.
Phil
P
Tozer
Siew C
SC
Ng
Muhammed R
MR
Siddiqui
Sophie
S
Plamondon
David
D
Burling
Arun
A
Gupta
Anna
A
Swatton
Sherrill
S
Tripoli
Carolynne J
CJ
Vaizey
Michael A
MA
Kamm
Robin
R
Phillips
Ailsa
A
Hart
D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D006801:Humans; D000069285:Infliximab; D008279:Magnetic Resonance Imaging; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D010502:Perineum / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012003:Rectal Fistula / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; C488629:azathiopurine; D000069285:Infliximab; D015122:Mercaptopurine; D000068879:Adalimumab