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, according to investigators.
These findings, and others concerning a lack of high-dose therapy and poor follow-up, suggest that more work is needed to optimize biologic therapy in this patient population, reported lead author Sabina Ali, MD, of UCSF Benioff Children’s Hospital, Oakland, California, and colleagues.
“With few medications available for treating CD, limited therapeutic longevity places patients at risk of exhausting treatment options,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is especially problematic for children, for whom infliximab and adalimumab remain the only medications approved by the Food and Drug Administration (FDA), and who require effective long-term therapy to maintain remission and prevent morbidity and disability for decades to come.”
Despite these concerns, reasons behind biologic discontinuation in the pediatric CD population have been poorly characterized, prompting the present study.
Dr. Ali and colleagues analyzed prospectively collected data from 823 patients treated at seven pediatric inflammatory bowel disease centers. Median age was 13 years, with slightly more male than female patients (60% vs 40%).
Within this group, 86% started biologics, most often infliximab (78%), followed by adalimumab (21%), and distantly, others (less than 1%). Most patients (86%) underwent TDM at some point during the treatment process, while one quarter (26%) took concomitant immunomodulators for at least 1 year.
Slightly less than one third of patients (29%) discontinued their first biologic after a median of approximately 2 years. The most common reason for discontinuation was inefficacy (34%), followed by nonadherence (12%), anti-drug antibodies (8%), and adverse events (8%).
Among those who discontinued due to inefficacy, 85% underwent prediscontinuation evaluation. When TDM of adalimumab or infliximab was performed prior to discontinuation, almost 2 out of 3 patients (62%) had drug levels lower than 10 µg/mL.
“We cannot determine the reasons dose escalation was not attempted,” the investigators wrote. “However, trough levels greater than 10 mg/mL may be associated with improved efficacy.”
Most patients (91%) who stopped their first biologic started a second, and more than one third (36%) also discontinued that second option, usually after about 1 year. After 4 years, only 10% of patients remained on their second biologic therapy. By study end, almost 1 out of 12 patients were on their third or fourth biologic, and 17% of patients were on a biologic currently not approved by the FDA.
Beyond characterizing these usage and discontinuation rates, the investigators also assessed factors associated with discontinuation or therapeutic persistence.
Proactive TDM was the strongest factor driving therapeutic persistence, as it reduced risk of discontinuation by 63%. Concomitant immunomodulatory therapy also reduced discontinuation risk, by 30%. Conversely, usage of 5-aminoasalicylate in the first 90 days of diagnosis was associated with a 70% higher discontinuation rate.
“The reason for this [latter finding about aminosalicylates] is not clear but may be an indicator of insurance-related or other barriers to care,” the investigators wrote.
Dr. Ali and colleagues concluded by noting how concerning, and commonplace, biologic discontinuation is in this patient population.
“This poses a serious problem for pediatric patients who will require treatment for decades to come,” they wrote. “Thoughtful strategies are needed to preserve treatment longevity and minimize the loss of treatment options.”
This work was supported by the Gary and Rachel Glick Charitable Fund. The investigators disclosed relationships with Janssen, Eli Lilly, AbbVie, and others.
As pediatric gastroenterologists, our practice has significantly changed over time, including the approach of using more effective medications sooner and adoption of therapeutic drug monitoring (TDM) as standard of care to optimize dosing. This study found the use of TDM during the induction phase of biologic therapy increased over the study duration from 2% to 70%, which is remarkable. Pediatric patients tend to have more extensive and severe disease, often necessitating higher dosing. With limited Food and Drug Administration–approved medications to treat children with IBD, it is imperative that we position these medications appropriately and be assertive with dose optimization to improve patient outcomes.
Alarmingly, one third of patients discontinued their biologic after 2.2 years. Concerningly, half discontinued their biologics without a trial of high-dose therapy and 14% without any evaluation. Trough levels >10 mg/mL may be associated with improved efficacy and low antibody levels can be overcome, however many of these patients had levels lower than this. This is likely a missed opportunity to capture response and increase durability with dose escalation. Biologic discontinuation was reduced by 60% with the use of proactive TDM and 32% with concomitant immunomodulators (on >12 months, compared with monotherapy). Pediatric data supporting the use of concomitant immunomodulators has been mixed.
As pediatric IBD physicians, we need to increase our diligence to optimize biologic therapy early. Early dose optimization could negate the observed protective impact from concomitant immunomodulator use in many cases, thereby decreasing risk of potential side effects. This highlights the importance of a shared decision-making discussion with our patients and families.
Further research is needed to address strategies to increase drug durability including TDM and dose optimization, adherence, health literacy, engagement, and the role for patient education to enhance medication optimization and durability.
Jennifer L. Dotson, MD, MPH, is chief of pediatric gastroenterology, hepatology, and nutrition at Arkansas Children’s Hospital and professor of pediatrics at the University of Arkansas for Medical Sciences, both in Little Rock. She declares no conflicts of interest.
As pediatric gastroenterologists, our practice has significantly changed over time, including the approach of using more effective medications sooner and adoption of therapeutic drug monitoring (TDM) as standard of care to optimize dosing. This study found the use of TDM during the induction phase of biologic therapy increased over the study duration from 2% to 70%, which is remarkable. Pediatric patients tend to have more extensive and severe disease, often necessitating higher dosing. With limited Food and Drug Administration–approved medications to treat children with IBD, it is imperative that we position these medications appropriately and be assertive with dose optimization to improve patient outcomes.
Alarmingly, one third of patients discontinued their biologic after 2.2 years. Concerningly, half discontinued their biologics without a trial of high-dose therapy and 14% without any evaluation. Trough levels >10 mg/mL may be associated with improved efficacy and low antibody levels can be overcome, however many of these patients had levels lower than this. This is likely a missed opportunity to capture response and increase durability with dose escalation. Biologic discontinuation was reduced by 60% with the use of proactive TDM and 32% with concomitant immunomodulators (on >12 months, compared with monotherapy). Pediatric data supporting the use of concomitant immunomodulators has been mixed.
As pediatric IBD physicians, we need to increase our diligence to optimize biologic therapy early. Early dose optimization could negate the observed protective impact from concomitant immunomodulator use in many cases, thereby decreasing risk of potential side effects. This highlights the importance of a shared decision-making discussion with our patients and families.
Further research is needed to address strategies to increase drug durability including TDM and dose optimization, adherence, health literacy, engagement, and the role for patient education to enhance medication optimization and durability.
Jennifer L. Dotson, MD, MPH, is chief of pediatric gastroenterology, hepatology, and nutrition at Arkansas Children’s Hospital and professor of pediatrics at the University of Arkansas for Medical Sciences, both in Little Rock. She declares no conflicts of interest.
As pediatric gastroenterologists, our practice has significantly changed over time, including the approach of using more effective medications sooner and adoption of therapeutic drug monitoring (TDM) as standard of care to optimize dosing. This study found the use of TDM during the induction phase of biologic therapy increased over the study duration from 2% to 70%, which is remarkable. Pediatric patients tend to have more extensive and severe disease, often necessitating higher dosing. With limited Food and Drug Administration–approved medications to treat children with IBD, it is imperative that we position these medications appropriately and be assertive with dose optimization to improve patient outcomes.
Alarmingly, one third of patients discontinued their biologic after 2.2 years. Concerningly, half discontinued their biologics without a trial of high-dose therapy and 14% without any evaluation. Trough levels >10 mg/mL may be associated with improved efficacy and low antibody levels can be overcome, however many of these patients had levels lower than this. This is likely a missed opportunity to capture response and increase durability with dose escalation. Biologic discontinuation was reduced by 60% with the use of proactive TDM and 32% with concomitant immunomodulators (on >12 months, compared with monotherapy). Pediatric data supporting the use of concomitant immunomodulators has been mixed.
As pediatric IBD physicians, we need to increase our diligence to optimize biologic therapy early. Early dose optimization could negate the observed protective impact from concomitant immunomodulator use in many cases, thereby decreasing risk of potential side effects. This highlights the importance of a shared decision-making discussion with our patients and families.
Further research is needed to address strategies to increase drug durability including TDM and dose optimization, adherence, health literacy, engagement, and the role for patient education to enhance medication optimization and durability.
Jennifer L. Dotson, MD, MPH, is chief of pediatric gastroenterology, hepatology, and nutrition at Arkansas Children’s Hospital and professor of pediatrics at the University of Arkansas for Medical Sciences, both in Little Rock. She declares no conflicts of interest.
, according to investigators.
These findings, and others concerning a lack of high-dose therapy and poor follow-up, suggest that more work is needed to optimize biologic therapy in this patient population, reported lead author Sabina Ali, MD, of UCSF Benioff Children’s Hospital, Oakland, California, and colleagues.
“With few medications available for treating CD, limited therapeutic longevity places patients at risk of exhausting treatment options,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is especially problematic for children, for whom infliximab and adalimumab remain the only medications approved by the Food and Drug Administration (FDA), and who require effective long-term therapy to maintain remission and prevent morbidity and disability for decades to come.”
Despite these concerns, reasons behind biologic discontinuation in the pediatric CD population have been poorly characterized, prompting the present study.
Dr. Ali and colleagues analyzed prospectively collected data from 823 patients treated at seven pediatric inflammatory bowel disease centers. Median age was 13 years, with slightly more male than female patients (60% vs 40%).
Within this group, 86% started biologics, most often infliximab (78%), followed by adalimumab (21%), and distantly, others (less than 1%). Most patients (86%) underwent TDM at some point during the treatment process, while one quarter (26%) took concomitant immunomodulators for at least 1 year.
Slightly less than one third of patients (29%) discontinued their first biologic after a median of approximately 2 years. The most common reason for discontinuation was inefficacy (34%), followed by nonadherence (12%), anti-drug antibodies (8%), and adverse events (8%).
Among those who discontinued due to inefficacy, 85% underwent prediscontinuation evaluation. When TDM of adalimumab or infliximab was performed prior to discontinuation, almost 2 out of 3 patients (62%) had drug levels lower than 10 µg/mL.
“We cannot determine the reasons dose escalation was not attempted,” the investigators wrote. “However, trough levels greater than 10 mg/mL may be associated with improved efficacy.”
Most patients (91%) who stopped their first biologic started a second, and more than one third (36%) also discontinued that second option, usually after about 1 year. After 4 years, only 10% of patients remained on their second biologic therapy. By study end, almost 1 out of 12 patients were on their third or fourth biologic, and 17% of patients were on a biologic currently not approved by the FDA.
Beyond characterizing these usage and discontinuation rates, the investigators also assessed factors associated with discontinuation or therapeutic persistence.
Proactive TDM was the strongest factor driving therapeutic persistence, as it reduced risk of discontinuation by 63%. Concomitant immunomodulatory therapy also reduced discontinuation risk, by 30%. Conversely, usage of 5-aminoasalicylate in the first 90 days of diagnosis was associated with a 70% higher discontinuation rate.
“The reason for this [latter finding about aminosalicylates] is not clear but may be an indicator of insurance-related or other barriers to care,” the investigators wrote.
Dr. Ali and colleagues concluded by noting how concerning, and commonplace, biologic discontinuation is in this patient population.
“This poses a serious problem for pediatric patients who will require treatment for decades to come,” they wrote. “Thoughtful strategies are needed to preserve treatment longevity and minimize the loss of treatment options.”
This work was supported by the Gary and Rachel Glick Charitable Fund. The investigators disclosed relationships with Janssen, Eli Lilly, AbbVie, and others.
, according to investigators.
These findings, and others concerning a lack of high-dose therapy and poor follow-up, suggest that more work is needed to optimize biologic therapy in this patient population, reported lead author Sabina Ali, MD, of UCSF Benioff Children’s Hospital, Oakland, California, and colleagues.
“With few medications available for treating CD, limited therapeutic longevity places patients at risk of exhausting treatment options,” the investigators wrote in Clinical Gastroenterology and Hepatology. “This is especially problematic for children, for whom infliximab and adalimumab remain the only medications approved by the Food and Drug Administration (FDA), and who require effective long-term therapy to maintain remission and prevent morbidity and disability for decades to come.”
Despite these concerns, reasons behind biologic discontinuation in the pediatric CD population have been poorly characterized, prompting the present study.
Dr. Ali and colleagues analyzed prospectively collected data from 823 patients treated at seven pediatric inflammatory bowel disease centers. Median age was 13 years, with slightly more male than female patients (60% vs 40%).
Within this group, 86% started biologics, most often infliximab (78%), followed by adalimumab (21%), and distantly, others (less than 1%). Most patients (86%) underwent TDM at some point during the treatment process, while one quarter (26%) took concomitant immunomodulators for at least 1 year.
Slightly less than one third of patients (29%) discontinued their first biologic after a median of approximately 2 years. The most common reason for discontinuation was inefficacy (34%), followed by nonadherence (12%), anti-drug antibodies (8%), and adverse events (8%).
Among those who discontinued due to inefficacy, 85% underwent prediscontinuation evaluation. When TDM of adalimumab or infliximab was performed prior to discontinuation, almost 2 out of 3 patients (62%) had drug levels lower than 10 µg/mL.
“We cannot determine the reasons dose escalation was not attempted,” the investigators wrote. “However, trough levels greater than 10 mg/mL may be associated with improved efficacy.”
Most patients (91%) who stopped their first biologic started a second, and more than one third (36%) also discontinued that second option, usually after about 1 year. After 4 years, only 10% of patients remained on their second biologic therapy. By study end, almost 1 out of 12 patients were on their third or fourth biologic, and 17% of patients were on a biologic currently not approved by the FDA.
Beyond characterizing these usage and discontinuation rates, the investigators also assessed factors associated with discontinuation or therapeutic persistence.
Proactive TDM was the strongest factor driving therapeutic persistence, as it reduced risk of discontinuation by 63%. Concomitant immunomodulatory therapy also reduced discontinuation risk, by 30%. Conversely, usage of 5-aminoasalicylate in the first 90 days of diagnosis was associated with a 70% higher discontinuation rate.
“The reason for this [latter finding about aminosalicylates] is not clear but may be an indicator of insurance-related or other barriers to care,” the investigators wrote.
Dr. Ali and colleagues concluded by noting how concerning, and commonplace, biologic discontinuation is in this patient population.
“This poses a serious problem for pediatric patients who will require treatment for decades to come,” they wrote. “Thoughtful strategies are needed to preserve treatment longevity and minimize the loss of treatment options.”
This work was supported by the Gary and Rachel Glick Charitable Fund. The investigators disclosed relationships with Janssen, Eli Lilly, AbbVie, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
