Test-and-treat approach best in Crohn's disease

In Crohn’s disease that is no longer responsive to infliximab, a testing-based strategy for regaining treatment efficacy is more cost-effective than is empiric dose escalation, wrote Dr. Fernando S. Velayos and colleagues. The study was published in the June issue of Clinical Gastroenterology and Hepatology.

In a decision analytical model conducted from the perspective of a third-party payer, Dr. Velayos of the University of California, San Francisco, looked at two cohorts of Crohn’s patients with loss of response to infliximab.

"The model included only infliximab and not other TNF antagonists given that, first, infliximab drug and antibody concentrations are the only commercial tests currently available in the United States, and, second, sufficient published data exist for infliximab to populate the necessary efficacy and cost inputs," he noted.

Quality-adjusted life years (QALYs) and costs were calculated based on a 1-year time horizon; costs included treatment and health state costs, but not indirect costs such as time missed from work, wrote the authors.

The base case in this model was a 35-year-old man weighing 70 kg with moderate to severe active ileocolonic Crohn’s disease who had achieved remission after infliximab induction, but experienced Crohn’s-like symptoms during maintenance. Additionally, the model assumed that nonbiologic therapies had already been exhausted, that the patient did not have Clostridium difficile, and that surgery was not warranted.

Each cohort was then subjected to one of two strategies: testing-based treatment or empiric treatment.

In the former strategy, all patients receive testing to detect antibodies to infliximab and quantify serum infliximab concentration.

Patients who had antibodies to infliximab were then switched to a different TNF antagonist, adalimumab.

Patients who lacked infliximab antibodies and did have a therapeutic serum concentration of the drug, on the other hand, underwent computerized tomography enterography and/or colonoscopy.

A finding of active inflammation meant surgery, and a finding of no active inflammation meant continuation of infliximab "for symptoms presumed caused by some other disease process that does not clearly justify immediate surgery or change in Crohn’s therapy."

The empiric strategy, meanwhile, followed guidance from the World Congress of Gastroenterology, whereby nonresponders first underwent an increase in the infliximab dose; if they still failed, they were switched to adalimumab.

Further failure meant an increased adalimumab dose, and, finally, if Crohn’s symptoms were still present, the patient proceeded to surgery.

Dr. Velayos found that the testing strategy yielded similar QALYs compared with the empiric strategy, at 0.801 versus 0.800, respectively. However, the testing approach to treatment was less expensive, at $31,870, compared with $37,266 for the empiric strategy.

The researchers also found that although the proportion of patients with response and in remission was similar at 1 year for both the testing and empiric cohort, "this was achieved differently."

Specifically, patients in the testing group underwent more surgery (48% versus 34% in the empiric group) and had substantially lower use of high-dose biological therapy (41% versus 54%).

In addition, more patients in the testing strategy were managed without biological therapy (34% versus 27%, respectively).

Moreover, "Even in situations in which the empiric strategy was not dominated by the testing strategy and thus an incremental cost-efficiency ratio was calculated, the estimates ranged between $500,000 to more than $5 million per QALY gained, well in excess of the $50,000 to $100,000 per QALY considered to be a reasonable cost-effectiveness threshold."

Several authors, including Dr. Velayos, disclosed ties with pharmaceutical companies. The researchers said the study was funded by Prometheus Laboratories, maker of diagnostic laboratory tests for use in Crohn’s disease and other conditions.

[email protected]

In Crohn’s disease that is no longer responsive to infliximab, a testing-based strategy for regaining treatment efficacy is more cost-effective than is empiric dose escalation, wrote Dr. Fernando S. Velayos and colleagues. The study was published in the June issue of Clinical Gastroenterology and Hepatology.

In a decision analytical model conducted from the perspective of a third-party payer, Dr. Velayos of the University of California, San Francisco, looked at two cohorts of Crohn’s patients with loss of response to infliximab.

"The model included only infliximab and not other TNF antagonists given that, first, infliximab drug and antibody concentrations are the only commercial tests currently available in the United States, and, second, sufficient published data exist for infliximab to populate the necessary efficacy and cost inputs," he noted.

Quality-adjusted life years (QALYs) and costs were calculated based on a 1-year time horizon; costs included treatment and health state costs, but not indirect costs such as time missed from work, wrote the authors.

The base case in this model was a 35-year-old man weighing 70 kg with moderate to severe active ileocolonic Crohn’s disease who had achieved remission after infliximab induction, but experienced Crohn’s-like symptoms during maintenance. Additionally, the model assumed that nonbiologic therapies had already been exhausted, that the patient did not have Clostridium difficile, and that surgery was not warranted.

Each cohort was then subjected to one of two strategies: testing-based treatment or empiric treatment.

In the former strategy, all patients receive testing to detect antibodies to infliximab and quantify serum infliximab concentration.

Patients who had antibodies to infliximab were then switched to a different TNF antagonist, adalimumab.

Patients who lacked infliximab antibodies and did have a therapeutic serum concentration of the drug, on the other hand, underwent computerized tomography enterography and/or colonoscopy.

A finding of active inflammation meant surgery, and a finding of no active inflammation meant continuation of infliximab "for symptoms presumed caused by some other disease process that does not clearly justify immediate surgery or change in Crohn’s therapy."

The empiric strategy, meanwhile, followed guidance from the World Congress of Gastroenterology, whereby nonresponders first underwent an increase in the infliximab dose; if they still failed, they were switched to adalimumab.

Further failure meant an increased adalimumab dose, and, finally, if Crohn’s symptoms were still present, the patient proceeded to surgery.

Dr. Velayos found that the testing strategy yielded similar QALYs compared with the empiric strategy, at 0.801 versus 0.800, respectively. However, the testing approach to treatment was less expensive, at $31,870, compared with $37,266 for the empiric strategy.

The researchers also found that although the proportion of patients with response and in remission was similar at 1 year for both the testing and empiric cohort, "this was achieved differently."

Specifically, patients in the testing group underwent more surgery (48% versus 34% in the empiric group) and had substantially lower use of high-dose biological therapy (41% versus 54%).

In addition, more patients in the testing strategy were managed without biological therapy (34% versus 27%, respectively).

Moreover, "Even in situations in which the empiric strategy was not dominated by the testing strategy and thus an incremental cost-efficiency ratio was calculated, the estimates ranged between $500,000 to more than $5 million per QALY gained, well in excess of the $50,000 to $100,000 per QALY considered to be a reasonable cost-effectiveness threshold."

Several authors, including Dr. Velayos, disclosed ties with pharmaceutical companies. The researchers said the study was funded by Prometheus Laboratories, maker of diagnostic laboratory tests for use in Crohn’s disease and other conditions.

[email protected]

In Crohn’s disease that is no longer responsive to infliximab, a testing-based strategy for regaining treatment efficacy is more cost-effective than is empiric dose escalation, wrote Dr. Fernando S. Velayos and colleagues. The study was published in the June issue of Clinical Gastroenterology and Hepatology.

In a decision analytical model conducted from the perspective of a third-party payer, Dr. Velayos of the University of California, San Francisco, looked at two cohorts of Crohn’s patients with loss of response to infliximab.

"The model included only infliximab and not other TNF antagonists given that, first, infliximab drug and antibody concentrations are the only commercial tests currently available in the United States, and, second, sufficient published data exist for infliximab to populate the necessary efficacy and cost inputs," he noted.

Quality-adjusted life years (QALYs) and costs were calculated based on a 1-year time horizon; costs included treatment and health state costs, but not indirect costs such as time missed from work, wrote the authors.

The base case in this model was a 35-year-old man weighing 70 kg with moderate to severe active ileocolonic Crohn’s disease who had achieved remission after infliximab induction, but experienced Crohn’s-like symptoms during maintenance. Additionally, the model assumed that nonbiologic therapies had already been exhausted, that the patient did not have Clostridium difficile, and that surgery was not warranted.

Each cohort was then subjected to one of two strategies: testing-based treatment or empiric treatment.

In the former strategy, all patients receive testing to detect antibodies to infliximab and quantify serum infliximab concentration.

Patients who had antibodies to infliximab were then switched to a different TNF antagonist, adalimumab.

Patients who lacked infliximab antibodies and did have a therapeutic serum concentration of the drug, on the other hand, underwent computerized tomography enterography and/or colonoscopy.

A finding of active inflammation meant surgery, and a finding of no active inflammation meant continuation of infliximab "for symptoms presumed caused by some other disease process that does not clearly justify immediate surgery or change in Crohn’s therapy."

The empiric strategy, meanwhile, followed guidance from the World Congress of Gastroenterology, whereby nonresponders first underwent an increase in the infliximab dose; if they still failed, they were switched to adalimumab.

Further failure meant an increased adalimumab dose, and, finally, if Crohn’s symptoms were still present, the patient proceeded to surgery.

Dr. Velayos found that the testing strategy yielded similar QALYs compared with the empiric strategy, at 0.801 versus 0.800, respectively. However, the testing approach to treatment was less expensive, at $31,870, compared with $37,266 for the empiric strategy.

The researchers also found that although the proportion of patients with response and in remission was similar at 1 year for both the testing and empiric cohort, "this was achieved differently."

Specifically, patients in the testing group underwent more surgery (48% versus 34% in the empiric group) and had substantially lower use of high-dose biological therapy (41% versus 54%).

In addition, more patients in the testing strategy were managed without biological therapy (34% versus 27%, respectively).

Moreover, "Even in situations in which the empiric strategy was not dominated by the testing strategy and thus an incremental cost-efficiency ratio was calculated, the estimates ranged between $500,000 to more than $5 million per QALY gained, well in excess of the $50,000 to $100,000 per QALY considered to be a reasonable cost-effectiveness threshold."

Several authors, including Dr. Velayos, disclosed ties with pharmaceutical companies. The researchers said the study was funded by Prometheus Laboratories, maker of diagnostic laboratory tests for use in Crohn’s disease and other conditions.

[email protected]