Post-Induction Levels of MMP3 Can Predict Loss of Response to Infliximab in IBD

Activated metalloproteinases degrade both matrix and nonmatrix proteins, and play a key role in wound healing, tissue repair, and response to injury. When dysregulated, they can also have a role in the progression of inflammatory diseases and malignancies.

It has been hypothesized that these metalloproteinases, and particularly MMP3, could a have a role in degrading anti—tumor necrosis factor (anti-TNF) drugs, leading to anti-TNF failure in patients with inflammatory bowel disease (IBD).

Now, research presented at the 14th Congress of the European Crohn’s and Colitis Organisation finds that, after induction with infliximab, high MMP3 levels predicted a loss of response among patients with IBD over the coming 12 months.

In the study, the investigators retrospectively reviewed the data of 73 patients with IBD, 37 of whom had ulcerative colitis and 36 of whom had Crohn disease. Among the 73 patients, 37 had responded to anti-TNF therapy with infliximab after 52 weeks, and 36 had not responded.

All patients had their MMP3 tested at baseline, after induction, and again at 1 year. Trough levels and antidrug antibodies (ADAs) were also recorded at 1 year. The investigators also sampled the MMP3 levels of 28 healthy volunteers as controls.

They found that, between responders and nonresponders to infliximab, serum levels at baseline were not significantly different. However, after induction, responders had levels of 8.68 ng/ml while nonresponders had levels of 25.7 ng/ml (P <.001). At 12 months, these values were 11.63 ng/ml and 29.72 ng/ml, respectively (P <.001).

Furthermore, among nonresponders with low trough levels, those who had high ADA levels and those who had no ADAs had similar MMP3 levels (32.01 and 24.56, respectively, P = .1), and there was a significant negative correlation between MMP3 levels and trough levels at 1 year in the overall population.

According to the authors, high MMP3 levels post-induction predict loss of response over the next year, and patients who are nonresponders to infliximab, regardless of ADAs, demonstrate high MMP3 levels.

Reference

Barberio B, D’Inca R, Facchin S, et al. Mechanisms of infliximab failure: the predictive role of MMP3. Presented at the 14th Congress of the European Crohn’s and Colitis Organisation; March 6-9, 2019; Copenhagen, Denmark. Abstract P650.