Adalimumab Sustains Remission for Crohn's Disease
Adalimumab Sustains Remission for Crohn's Disease
Background Treatments that achieve sustainable steroid-free clinical remission in Crohn's disease are needed; however, long-term steroid-sparing efficacy data are limited.
Aim To evaluate steroid-sparing efficacy and the impact of steroid discontinuation on adverse events during treatment of Crohn's disease with adalimumab in the phase III randomised, double-blind 1-year CHARM trial and for an additional 2 years in its open-label extension ADHERE.
Methods Steroid-free remission and response and steroid-sparing (≥50% steroid dose reduction) remission rates were evaluated over 3 years in patients who were taking corticosteroids at CHARM baseline.
Results Of 778 patients randomised in CHARM (including those who did not achieve clinical response to open-label induction therapy), 313 patients (40%) were on corticosteroids at baseline. In the 206 patients randomised to adalimumab, rates of steroid-free remission at 1 year and 3 years were 26% and 23% respectively; corresponding rates were 29% and 25% for steroid-sparing remission and 32% and 28% for steroid-free response. Although the incidence of serious infections with adalimumab treatment during CHARM was higher in patients taking steroids at baseline than those who were not, the rates of overall adverse events, serious infections and opportunistic infections were lower in patients who were able to discontinue corticosteroids than those who remained on steroids.
Conclusion Adalimumab therapy resulted in modest but clinically meaningful rates of steroid-free remission, sustained over 3 years of treatment, in a heavily pretreated population of patients with Crohn's disease receiving steroids at the start of therapy (http://www.clinicaltrials.gov number: NCT00077779).
Crohn's disease (CD) is a chronic, progressive inflammatory disease of the gastrointestinal tract. Corticosteroids are effective in inducing remission in 60–93% of patients with moderate to severe CD. However, their toxicity and ability to maintain remission are areas of concern. Despite the use of immunosuppressants, such as azathioprine, a significant proportion of patients will remain steroid-dependent. The early need for steroids for symptom control may be a negative prognostic marker for CD outcome.
Steroids exert anti-inflammatory effects by binding to intracellular receptors present in all human cells, and can therefore produce a wide range of systemic adverse effects. Side effects that are most concerning include osteoporosis, diabetes, hypertension, glaucoma, cataracts, potentially lethal infections and an increased risk of mortality.
There is a need for long-term treatment alternatives that maintain clinical remission and reduce exposure to corticosteroids. Data regarding the long-term (i.e. beyond 1 year) steroid-sparing effect of maintenance medications, including antitumour necrosis factor (TNF) therapies, are limited.
Adalimumab is a fully human monoclonal antibody specific to TNF that is widely approved for the treatment of CD. This post hoc analysis of the pivotal CHARM maintenance trial evaluated steroid tapering and steroid-free remission during treatment with adalimumab in CHARM and through 2 years of the ADHERE open-label extension trial, for all randomised patients, including those who had not achieved clinical response after open-label induction therapy at week 4 of CHARM. This analysis builds upon analyses of steroid-free remission during year 1 for the patients who achieved clinical response after induction therapy reported in the original CHARM publication and is the first multi-year report of steroid-sparing efficacy of an anti-TNF agent in a large clinical trial cohort.
Abstract and Introduction
Abstract
Background Treatments that achieve sustainable steroid-free clinical remission in Crohn's disease are needed; however, long-term steroid-sparing efficacy data are limited.
Aim To evaluate steroid-sparing efficacy and the impact of steroid discontinuation on adverse events during treatment of Crohn's disease with adalimumab in the phase III randomised, double-blind 1-year CHARM trial and for an additional 2 years in its open-label extension ADHERE.
Methods Steroid-free remission and response and steroid-sparing (≥50% steroid dose reduction) remission rates were evaluated over 3 years in patients who were taking corticosteroids at CHARM baseline.
Results Of 778 patients randomised in CHARM (including those who did not achieve clinical response to open-label induction therapy), 313 patients (40%) were on corticosteroids at baseline. In the 206 patients randomised to adalimumab, rates of steroid-free remission at 1 year and 3 years were 26% and 23% respectively; corresponding rates were 29% and 25% for steroid-sparing remission and 32% and 28% for steroid-free response. Although the incidence of serious infections with adalimumab treatment during CHARM was higher in patients taking steroids at baseline than those who were not, the rates of overall adverse events, serious infections and opportunistic infections were lower in patients who were able to discontinue corticosteroids than those who remained on steroids.
Conclusion Adalimumab therapy resulted in modest but clinically meaningful rates of steroid-free remission, sustained over 3 years of treatment, in a heavily pretreated population of patients with Crohn's disease receiving steroids at the start of therapy (http://www.clinicaltrials.gov number: NCT00077779).
Introduction
Crohn's disease (CD) is a chronic, progressive inflammatory disease of the gastrointestinal tract. Corticosteroids are effective in inducing remission in 60–93% of patients with moderate to severe CD. However, their toxicity and ability to maintain remission are areas of concern. Despite the use of immunosuppressants, such as azathioprine, a significant proportion of patients will remain steroid-dependent. The early need for steroids for symptom control may be a negative prognostic marker for CD outcome.
Steroids exert anti-inflammatory effects by binding to intracellular receptors present in all human cells, and can therefore produce a wide range of systemic adverse effects. Side effects that are most concerning include osteoporosis, diabetes, hypertension, glaucoma, cataracts, potentially lethal infections and an increased risk of mortality.
There is a need for long-term treatment alternatives that maintain clinical remission and reduce exposure to corticosteroids. Data regarding the long-term (i.e. beyond 1 year) steroid-sparing effect of maintenance medications, including antitumour necrosis factor (TNF) therapies, are limited.
Adalimumab is a fully human monoclonal antibody specific to TNF that is widely approved for the treatment of CD. This post hoc analysis of the pivotal CHARM maintenance trial evaluated steroid tapering and steroid-free remission during treatment with adalimumab in CHARM and through 2 years of the ADHERE open-label extension trial, for all randomised patients, including those who had not achieved clinical response after open-label induction therapy at week 4 of CHARM. This analysis builds upon analyses of steroid-free remission during year 1 for the patients who achieved clinical response after induction therapy reported in the original CHARM publication and is the first multi-year report of steroid-sparing efficacy of an anti-TNF agent in a large clinical trial cohort.
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