Immunosuppressant Medications and Mortality in Inflammatory Bowel Disease
Immunosuppressant Medications and Mortality in Inflammatory Bowel Disease
Objective: This study examined whether treatment of Crohn's disease (CD) and ulcerative colitis (UC) with immunosuppressant medications was associated with an increased risk of death in the era prior to antitumor necrosis factor (TNF) therapies.
Design: This retrospective cohort study used data from the General Practice Research Database from 1987 to 1997. CD and UC patients were matched to controls on age, sex, and primary care practice. CD and UC patients were stratified according to whether they used immunosuppressant medications during follow-up. Cox proportional hazards models adjusted for comorbidities were used to define the relative hazard of death. Additional models examined the relative hazard of death with current use of corticosteroids or thiopurines.
Results: The cohort included 5,539 patients with CD, 8,910 patients with UC, and 41,624 controls. Patients with CD had an increased mortality (not immunosuppressant-treated CD hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.07–1.51; immunosuppressant-treated CD HR 2.44, 95% CI 1.84–3.25). Increased mortality was only observed among UC patients treated with immunosuppressant medications (HR 1.67, 95% CI 1.34–2.09). In both CD and UC, current corticosteroid therapy was associated with increased mortality (CD HR 2.48, 95% CI 1.85–3.31; UC HR 2.81, 95% CI 2.26–3.50). Current use of thiopurines was not associated with increased mortality (CD HR 0.83, 95% CI 0.37–1.86; UC HR 0.70, 95% CI 0.29–1.70).
Conclusions: Patients treated with corticosteroids, but not thiopurines, are at increased risk of death, although this study could not clarify whether this was as a result of the medication or the underlying disease severity.
The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing illnesses that may affect more than 1 million Americans. The goal of therapy is to bring acute flares under control and to maintain remission for as long as possible. To accomplish this, patients are often exposed to medications that suppress the immune system. Corticosteroids, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate, and antitumor necrosis factor (TNF)-α agents are effective and widely used to treat both CD and UC.
Previous studies demonstrated that patients with IBD, particularly CD, have an increased risk of mortality compared with the general population. Possible reasons for the increased mortality include complications of severe IBD or adverse effects of medical therapies, including serious infection and cancer. For example, a cohort study of patients treated with infliximab demonstrated that approximately 1% of patients died within 1 yr of initiating treatment. However, there was no control group in that study, so it was not clear whether the mortality was related to the treatment or the underlying disease. Limited data suggest that use of corticosteroids to treat CD and UC is strongly associated with patient mortality, while the same has not been observed for thiopurines or anti-TNF drugs. Specifically, the Crohn's Therapy, Resource, Evaluation and Assessment Tool (TREAT) registry data demonstrated a two-fold increased mortality among corticosteroid-treated patients with CD, but no increased mortality risk with infliximab (odds ratio [OR] 1.0) or immunomodulators (AZA, 6-MP, or methotrexate) (OR 0.7). In this study, we sought to determine: (a) whether patients with IBD are at increased risk for mortality compared with the general population, (b) whether any increased risk of mortality was limited to patients with severe disease requiring treatment with immunosuppressant medications and who would be likely candidates for treatment with anti-TNF and/or other novel therapies, and (c) whether the increased risk of mortality persisted after immunosuppressant medications were discontinued.
Objective: This study examined whether treatment of Crohn's disease (CD) and ulcerative colitis (UC) with immunosuppressant medications was associated with an increased risk of death in the era prior to antitumor necrosis factor (TNF) therapies.
Design: This retrospective cohort study used data from the General Practice Research Database from 1987 to 1997. CD and UC patients were matched to controls on age, sex, and primary care practice. CD and UC patients were stratified according to whether they used immunosuppressant medications during follow-up. Cox proportional hazards models adjusted for comorbidities were used to define the relative hazard of death. Additional models examined the relative hazard of death with current use of corticosteroids or thiopurines.
Results: The cohort included 5,539 patients with CD, 8,910 patients with UC, and 41,624 controls. Patients with CD had an increased mortality (not immunosuppressant-treated CD hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.07–1.51; immunosuppressant-treated CD HR 2.44, 95% CI 1.84–3.25). Increased mortality was only observed among UC patients treated with immunosuppressant medications (HR 1.67, 95% CI 1.34–2.09). In both CD and UC, current corticosteroid therapy was associated with increased mortality (CD HR 2.48, 95% CI 1.85–3.31; UC HR 2.81, 95% CI 2.26–3.50). Current use of thiopurines was not associated with increased mortality (CD HR 0.83, 95% CI 0.37–1.86; UC HR 0.70, 95% CI 0.29–1.70).
Conclusions: Patients treated with corticosteroids, but not thiopurines, are at increased risk of death, although this study could not clarify whether this was as a result of the medication or the underlying disease severity.
The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are chronic relapsing illnesses that may affect more than 1 million Americans. The goal of therapy is to bring acute flares under control and to maintain remission for as long as possible. To accomplish this, patients are often exposed to medications that suppress the immune system. Corticosteroids, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate, and antitumor necrosis factor (TNF)-α agents are effective and widely used to treat both CD and UC.
Previous studies demonstrated that patients with IBD, particularly CD, have an increased risk of mortality compared with the general population. Possible reasons for the increased mortality include complications of severe IBD or adverse effects of medical therapies, including serious infection and cancer. For example, a cohort study of patients treated with infliximab demonstrated that approximately 1% of patients died within 1 yr of initiating treatment. However, there was no control group in that study, so it was not clear whether the mortality was related to the treatment or the underlying disease. Limited data suggest that use of corticosteroids to treat CD and UC is strongly associated with patient mortality, while the same has not been observed for thiopurines or anti-TNF drugs. Specifically, the Crohn's Therapy, Resource, Evaluation and Assessment Tool (TREAT) registry data demonstrated a two-fold increased mortality among corticosteroid-treated patients with CD, but no increased mortality risk with infliximab (odds ratio [OR] 1.0) or immunomodulators (AZA, 6-MP, or methotrexate) (OR 0.7). In this study, we sought to determine: (a) whether patients with IBD are at increased risk for mortality compared with the general population, (b) whether any increased risk of mortality was limited to patients with severe disease requiring treatment with immunosuppressant medications and who would be likely candidates for treatment with anti-TNF and/or other novel therapies, and (c) whether the increased risk of mortality persisted after immunosuppressant medications were discontinued.
