Infliximab reverses inflammatory muscle wasting (sarcopenia) in Crohn's disease

Background Muscle wasting or sarcopenia arising from chronic inflammation is found in 60% of patients with Crohn's disease. Transcriptional protein NF-kappa B reduces muscle formation through MyoD transcription and increases muscle breakdown by proteolysis. Aim As TNF is a potent activator of NF-kappa B, and anti-TNF agent infliximab (IFX) prevents NF-kappa B activation, to determine whether or not Crohn's patients treated with IFX gain muscle volume and strength. Methods We performed a prospective, repeated-measures cohort study in adult Crohn's disease patients with an acute disease flare. Patients were instructed not to vary diet or activity. Concomitant medications were kept stable. At week 1 (pretreatment), week 16 (post-IFX induction) and week 25 (post-first IFX maintenance dose), we assessed (i) MRI volume of quadriceps femoris at anatomical mid-thigh; (ii) maximal concentric quadriceps contractions strength at three specific speeds of contraction; (iii) physical activity by validated instrument (IPAQ); (iv) Three-day food record of intake and composition (food-weighing method); (v) Serum levels of IL6. Results Nineteen patients (58% female; mean age 33.2 +/- 10.7 years) were recruited. IFX increased muscle volume in both legs from baseline (right, 1505 cm(3)) to week 25 (right, 1569 cm(3); P = 0.010). IFX also increased muscle strength in both legs from baseline (right 30 degrees/s, 184.8 Nm) to week 25 (right 30 degrees/s, 213.6 Nm; P = 0.002). Muscle volume gain correlated with male gender (P = 0.003). Significant gains in muscle volume and strength were unrelated to prednisolone use. Serum IL6 levels decreased by week 25 (P = 0.037). Conclusion The anti-TNF agent infliximab reverses inflammatory sarcopenia in patients with Crohn's disease.