Monday, June 17, 2013

Baricitinib at the EULAR 2013 meeting

I had been very enthusiastic about baricitinib (a novel oral inhibitor of JAK1/2) after the ACR 2012; see link below. And now I was in front of this poster telling me not to worry about cholesterol. But let's look at the study frist.

J. Kremer and colleagues presented [THU0226]: "Baricitinib effects on serum cholesterol and circulating lipid particles in a phase 2b study in patients with rheumatoid arthritis". In results the authors start with: " Baricitinib treatment resulted in a dose and time dependent increase relative to PB in LDL, HDL and total cholesterol detectable by Week 2." And then it gets very complicated. O.K. science is complicated. We'll get an overload of date, which you should read in the abstract. Let's move to the conclusions, which I'd like to quote in whole: "The increase in LDL cholesterol with baricitinib treatment is attributed to a shift towards larger particles rather than to an overall increase in LDL particle number at Week 12 and persisting through 24 weeks. In contrast, the changes observed in HDL cholesterol were associated with an increase in the total number of HDL particles by Week 12 and persisting through 24 weeks. Literature suggests that larger LDL particles are less atherogenic although this study does not address this correlation." To me it looks like an attempt to calm the waves. There is an increase in cholesterol, but don't worry. But now I am worried! Needless to say, but there has been a big disappointment, when I was looking at the poster.

P. Taylor and colleagues presented [OP0047]: "Baricitinib, an oral janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and efficacy in open-label, long-term extension study". In results you find: "Among pts who received 8 mg at any time (n=93), TEAEs occurred in 59 (63%), SAEs in 8 (9%), infections in 37 (40%) and serious infections in 2 (2%). No opportunistic infections or TB cases were observed." 9% SAE and 40% infections should be an issue! Conclusions: "Among pts completing 52 weeks of a phase 2b study, clinical improvements observed at week 24 were maintained or improved during the open label extension. In addition, safety signals observed over the open label extension were consistent with previously reported results of baricitinib." It's an extension study, so there can't be a placebo group. The clinical improvements are comparable to data from studies on biologics or methotrexate.

Let's see how things develop, FDA and EMEA are getting stricter in applying drug efficiency and safety requirements as seen in the recent ruling of EMEA concerning tofacitinib; the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) had adopted a negative opinion for Xeljanz® (tofacitinib) [treatment of adult patients with moderate to severe active rheumatoid arthritis]. The ACR20 response for instance looked good in the study above and despite my new worries and disappointments I still hope that baricitinib will make it to the market.

PS. Baricitinib has been known formerly as LY3009104/INCB028050.


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