Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.
OBJECTIVE
It has been variably suggested that nonselective NSAIDs and cyclooxygenase (COX)-2 selective inhibitors aggravate or ameliorate clinical disease activity in patients with inflammatory bowel disease. We assessed the effect of these drugs in patients with inflammatory bowel disease (n = 209) and the possible mechanisms.


METHODS
First, patients with quiescent Crohn's disease and ulcerative colitis received the non-NSAID analgesic acetaminophen (n = 26) and the conventional NSAIDs naproxen (n = 32), diclofenac (n = 29), and indomethacin (n = 22) for 4 weeks. The Harvey-Bradshaw index was used to define relapse. Second, to assess the mechanism of relapse, intestinal inflammation was quantitated (fecal calprotectin) before and during treatment (20 patients/group) with acetaminophen, naproxen (topical effect, COX-1 and -2 inhibitor), nabumetone (COX-1 and -2 inhibitor), nimesulide (selective COX-2 inhibitor), and low-dose aspirin (selective COX-1 inhibition).


RESULTS
Nonselective NSAIDs were associated with a 17%-28% relapse rate within 9 days of ingestion. No patient had an early relapse on acetaminophen, nimesulide, or aspirin, whereas those on naproxen and nabumetone (20%) experienced relapse. These clinical relapses were associated with escalating intestinal inflammatory activity.


CONCLUSIONS
NSAID ingestion is associated with frequent and early clinical relapse of quiescent inflammatory bowel disease, and the mechanism appears to be due to dual inhibition of the COX enzymes. Selective COX-2 inhibition with nimesulide and COX-1 inhibition with low-dose aspirin appear to be well-tolerated in the short-term.
Department of Internal Medicine, Guy's, King's, St Thomas' Medical School, London, United Kingdom.
Ken
K
Takeuchi
Simon
S
Smale
Purushothaman
P
Premchand
Laurence
L
Maiden
Roy
R
Sherwood
Bjarni
B
Thjodleifsson
Einar
E
Bjornsson
Ingvar
I
Bjarnason
D000082:Acetaminophen / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects; D002074:Butanones / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000503:physiopathology; D003424:Crohn Disease / Q000503:physiopathology; D051545:Cyclooxygenase 1; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D004008:Diclofenac / Q000009:adverse effects; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000009:adverse effects; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000077430:Nabumetone; D009288:Naproxen / Q000009:adverse effects; D015995:Prevalence; D012008:Recurrence; D013449:Sulfonamides / Q000009:adverse effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; D004008:Diclofenac; D000082:Acetaminophen; D009288:Naproxen; D051545:Cyclooxygenase 1; D000077430:Nabumetone; D001241:Aspirin; C012655:nimesulide; D007213:Indomethacin