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Importantly, the expression and impact of these genetic factors are further modulated by epigenetic mechanisms such as DNA methylation and histone modifications [49, 53,54,55, 59, 273]

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For example, if a patient with Crohns disease is on an anti-TNF therapy and has had some improvement in their intestinal symptoms but still has active perianal fistulas or persistent inflammation on endoscopy, I may consider adding a second agent to target a different pathway. In contrast, if that same patient had no meaningful improvement at all despite adequate drug levels [in the blood], I would be more likely to switch to a different class of therapy rather than stack," Ali says