The incidence of gastrointestinal perforations among rheumatoid arthritis patients.
OBJECTIVE
Gastrointestinal (GI) perforation has emerged as a novel safety concern in relation to medications used to treat rheumatoid arthritis (RA). This study was undertaken to characterize the incidence and risk factors for GI perforation in RA patients.


METHODS
Using administrative databases of a large US health plan, we identified RA patients treated with biologic agents, methotrexate (MTX), oral glucocorticoids, and nonsteroidal antiinflammatory drugs (NSAIDs). Additional risk factors we evaluated included diverticulitis. Hospitalization with GI perforation was identified using a validated algorithm. Incidence rates and risk factors were evaluated using Cox proportional hazards models.


RESULTS
Among 40,841 RA patients, 37 hospitalizations with GI perforation were identified. The rate of GI perforation among patients currently being treated with biologic agents who were also receiving oral glucocorticoids was higher (1.12 per 1,000 person-years [95% confidence interval (95% CI) 0.50-2.49]) than for patients being treated with biologic agents who were not also receiving glucocorticoids (0.47 per 1,000 person-years [95% CI 0.22-0.98]) or for patients being treated with MTX who were also receiving glucocorticoids (0.87 per 1,000 person-years [95% CI 0.36-2.10]). Neither biologic agents nor MTX was significantly associated with GI perforation, in contrast to current treatment with glucocorticoids and NSAIDs together (hazard ratio 4.7 [95% CI 1.9-12.0]) or glucocorticoids alone (hazard ratio 2.8 [95% CI 1.3-6.1]). Diverticulitis also was a strong risk factor (hazard ratio 9.1 [95% CI 3.1-26.4]). Seventy percent of patients with GI perforation received glucocorticoids, had antecedent diverticulitis, or both.


CONCLUSIONS
GI perforation is an uncommon but serious adverse event among RA patients. Because a majority of patients with GI perforation were being treated with glucocorticoids or had previously experienced diverticulitis, these individuals should be considered at higher risk.
Curtis
Jeffrey R
JR
University of Alabama at Birmingham, Birmingham, AL 35294, USA. jcurtis@uab.edu
Xie
Fenglong
F
Chen
Lang
L
Spettell
Claire
C
McMahan
Raechele M
RM
Fernandes
Joaquim
J
Delzell
Elizabeth
E
D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D015897:Comorbidity; D016208:Databases, Factual; D004238:Diverticulitis / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007416:Intestinal Perforation / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors
D018501:Antirheumatic Agents; D005938:Glucocorticoids