BACKGROUND: C iclosporine ( CsA), Tacrolimus (Tcl) and
Infliximab (IFX) are effective rescue therapies in steroidrefractory
ulcerative colitis (UC). Comparative studies are
however m issing. M ETHOD: T his i s the retrospective
analysis of treatment outcome for oral Tcl (n=27, initially
0.05mg/Kg twice daily, aiming for serum trough levels of
5-10 n g/mL), i ntravenous C sA ( n=23, 2 mg/kg/daily a nd
then o ral CsA 5mg/kg/daily) and IFX ( n=43, 5 mg/kg
intravenously at week 0, 2, 6 and then every 8 weeks) in
patients with s teroid r efractory moderate to s evere UC
enrolled i n the SWISS IBD cohort s tudy. After successful
rescue therapy with Tcl o r C sA, t hiopurine m aintenance
therapy or maintenance therapy with Tcl (in Tcl pretreated
patients) was introduced. The endpoints analyzed steroid
free r emission r ate (on the basis of m odified Truelove-
Witts severity index (MTWSI)) and number of colectomies
after 6 m onths. R ESULTS: A t 6 months, 26% ( 7/27) o f
patients treated with T cl r emained i n steroid free
remission (MTWSI score ≤4) compared to 30 % (7/23) on
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droplets to the same extend under the linoleic acid treat, whereas lipid hydrolysis or loss was
significantly increased in Huh-7 WT cells after 24h.
Conclusions: Chronic alcohol feeding in obese, insulin-resistant rats exerts significant and
synergistic effects on PNPLA3 mRNA expression, which correlated with triglyceride content.
In v itro experiments suggest that PNPLA3 expression depends on the t ypes of d ietary f atty
acids with polyunsaturated fatty a cids i nducing a nd monounsaturated fatty a cids inhibiting
PNPLA3 mRNA. I148M polymorphism of PNPLA3 l eads to attenuation o f lipolytic
processes resulting in fat accumulation in the cell.
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CsA and 58% ( 27/41) o f patients t reated w ith IFX ( Tcl &
CsA vs I FX p = 0 .018). S ignificant m ore patients had
primary non response, loss of response or severe adverse
events i n the CsA cohort ( 61%, 1 4/23) c ompared to Tcl
cohort (33.3 % , 9/27), and IFX cohort (30%, 1 3/43) (p=
0.037). Colectomy rate was significantly higher after CsA
(17.4 %, 4/23) compared to Tcl (3.7 %, 1/27) or IFX (2.3 %,
1/43) (p= 0.047).CONCLUSION: After s ix m onth, rescue
therapy with I FX h ad t he l owest c olectomy r ate,
significantly h igher steroid free r emission rate, a nd t he
lowest rate of non-response, loss of response and severe
adverse events compared to CsA or Tcl rescue treatment.