Highlights in Clinical IBD
Highlights in Clinical IBD
Carbonnel and colleagues reported the results of a prospective, multicenter, randomized controlled trial assessing methotrexate subcutaneously or intramuscularly vs placebo in patients with steroid-dependent ulcerative colitis.
The superiority of methotrexate vs placebo in reaching success at 16 weeks (defined by a Mayo score ≤ 2 with no item > 1 and complete steroid withdrawal) was not statistically significant. Secondary endpoints such as clinical remission without steroids at week 16 were observed in 42% of patients who received methotrexate compared with 23.5% of patients who were given placebo.
Although parenteral methotrexate was not significantly superior to placebo for the primary endpoint, steroid-free remissions were noted in a significantly larger percentage of patients. Results from the MERIT-UC trial of methotrexate for steroid-dependent UC are anxiously awaited.
Therapeutic drug monitoring for biologic therapy has increasingly come into practice as an effective way to assess and treat secondary loss of response to anti-TNF agents in patients with IBD. However, therapeutic drug monitoring based on trough levels has some obstacles, including the delay between the assessment of trough levels and dose adjustments at the following infusion.
In an attempt to obviate the delay in dose adjustments, Hoekman and colleagues investigated the relationship between infliximab concentrations at trough and intermediate infliximab concentrations at 4 and 6 weeks after maintenance infusions in patients with Crohn disease who were in clinical remission. Preliminary linear regression analysis showed an excellent correlation between infliximab concentrations at 4 and 6 weeks after infusion and 8-week trough levels.
Hopefully, these and other data will confirm an algorithm predicting trough levels far enough in advance to allow for dose-adjustments on a timelier basis.
Several studies presented at the meeting addressed pregnancy and lactation.
Julsgaard and colleagues examined the cord blood of 80 newborns who were exposed to infliximab or adalimumab and correlated the drug levels with maternal levels. Both multivariate and logistic regression analyses were used to determine factors that correlate with drug levels at the time of birth and clearance. The investigators described a strong correlation between cord blood and maternal blood. As expected, an inverse correlation was found between time since last exposure and both maternal and cord drug levels. Of note, the median time to clearance was 6 months for both infliximab and adalimumab. Blood levels were significantly lower when the drug was stopped prior to gestational week 30, and the median time to clearance was 6 months. The investigators found no increased risk for adverse pregnancy or developmental outcomes but noted that clearance in some neonates took up to 12 months, which may affect recommendations for live vaccines unless clearance is documented.
The ongoing PIANO study that is sponsored by the Crohn's and Colitis Foundation of America is evaluating a large cohort of pregnant women with IBD. One aim of the study was to determine whether biologics are detectable in breast milk and whether breastfeeding while on biologics or immunosuppressive drugs affects infections, growth, and development in children born to mothers with IBD. The investigators were able to obtain samples from 20 mothers (11 receiving infliximab, 6 adalimumab, and 3 certolizumab). They reported that women on immunosuppressive drugs were less likely to breastfeed than women who were biologic-exposed or un-exposed, even though the duration of breastfeeding was similar in all groups (approximately 7 months). The mean infant weight and height increase during the first year did not differ based on in utero drug exposure, third-trimester exposure, or breastfeeding, and infant milestone achievements were similar in all groups up to 12 months. Infection rates after the first year were similar in breastfed infants whether they were exposed to any medical therapy or not. Although the observational trial is continuing, these results provide reassurance about the safety of anti-TNF biologics during pregnancy and breastfeeding.
Methotrexate for Steroid-Dependent Ulcerative Colitis
Carbonnel and colleagues reported the results of a prospective, multicenter, randomized controlled trial assessing methotrexate subcutaneously or intramuscularly vs placebo in patients with steroid-dependent ulcerative colitis.
The superiority of methotrexate vs placebo in reaching success at 16 weeks (defined by a Mayo score ≤ 2 with no item > 1 and complete steroid withdrawal) was not statistically significant. Secondary endpoints such as clinical remission without steroids at week 16 were observed in 42% of patients who received methotrexate compared with 23.5% of patients who were given placebo.
Although parenteral methotrexate was not significantly superior to placebo for the primary endpoint, steroid-free remissions were noted in a significantly larger percentage of patients. Results from the MERIT-UC trial of methotrexate for steroid-dependent UC are anxiously awaited.
Accelerated Dose Adjustments for IBD
Therapeutic drug monitoring for biologic therapy has increasingly come into practice as an effective way to assess and treat secondary loss of response to anti-TNF agents in patients with IBD. However, therapeutic drug monitoring based on trough levels has some obstacles, including the delay between the assessment of trough levels and dose adjustments at the following infusion.
In an attempt to obviate the delay in dose adjustments, Hoekman and colleagues investigated the relationship between infliximab concentrations at trough and intermediate infliximab concentrations at 4 and 6 weeks after maintenance infusions in patients with Crohn disease who were in clinical remission. Preliminary linear regression analysis showed an excellent correlation between infliximab concentrations at 4 and 6 weeks after infusion and 8-week trough levels.
Hopefully, these and other data will confirm an algorithm predicting trough levels far enough in advance to allow for dose-adjustments on a timelier basis.
Drug Safety in Pregnancy and Lactation
Several studies presented at the meeting addressed pregnancy and lactation.
Julsgaard and colleagues examined the cord blood of 80 newborns who were exposed to infliximab or adalimumab and correlated the drug levels with maternal levels. Both multivariate and logistic regression analyses were used to determine factors that correlate with drug levels at the time of birth and clearance. The investigators described a strong correlation between cord blood and maternal blood. As expected, an inverse correlation was found between time since last exposure and both maternal and cord drug levels. Of note, the median time to clearance was 6 months for both infliximab and adalimumab. Blood levels were significantly lower when the drug was stopped prior to gestational week 30, and the median time to clearance was 6 months. The investigators found no increased risk for adverse pregnancy or developmental outcomes but noted that clearance in some neonates took up to 12 months, which may affect recommendations for live vaccines unless clearance is documented.
The ongoing PIANO study that is sponsored by the Crohn's and Colitis Foundation of America is evaluating a large cohort of pregnant women with IBD. One aim of the study was to determine whether biologics are detectable in breast milk and whether breastfeeding while on biologics or immunosuppressive drugs affects infections, growth, and development in children born to mothers with IBD. The investigators were able to obtain samples from 20 mothers (11 receiving infliximab, 6 adalimumab, and 3 certolizumab). They reported that women on immunosuppressive drugs were less likely to breastfeed than women who were biologic-exposed or un-exposed, even though the duration of breastfeeding was similar in all groups (approximately 7 months). The mean infant weight and height increase during the first year did not differ based on in utero drug exposure, third-trimester exposure, or breastfeeding, and infant milestone achievements were similar in all groups up to 12 months. Infection rates after the first year were similar in breastfed infants whether they were exposed to any medical therapy or not. Although the observational trial is continuing, these results provide reassurance about the safety of anti-TNF biologics during pregnancy and breastfeeding.
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