Crohn’s: Novel biomarker predicts early responses to anti-TNF therapy

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.