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FDA Approves Low Dose Baricitinib for Rheumatoid Arthritis

The US Food and Drug Administration has approved baricitinib (Olumiant) for use in adults in moderate-to-severe active rheumatoid arthritis (RA) who have had an inadequate response to TNF inhibitors (TNFi). It is not approved for use, nor has it been studied, in children.

This action follows the recommendation of the Arthritis Advisory Committee panel that met on April 23rd, and recommended approval of the lower 2mg dose of baricitinib, noting that data for the 4 mg dose failed to show greater efficacy. The panel also had additional safety concerns with the higher dose, especially with regard to venous thromboembolic events (VTE).

Currently Oluminant is approved in over 40 countries at both the 2 mg and 4 mg doses, where there is also a warning for VTE. 

Full prescribing information can be found here.  Some of the highlights from the product label include:

  • Boxed warning for serious infections, TB risk and need for TB testing and monitoring, risk of neoplasia and lymphoma and the risk of VTE (including DVT, PE)
  • May be used as monotherapy or in combination with methotrexate or other DMARDs
  • Dose: 2 mg once daily (Half-life is 12 hours in RA and is primarily (75%) excreted in the urine.
  • The drug was approved based on 2 dose ranging studies and 2 phase III trials involving a total of 1253 RA patients.
  • Limitation of Use: in patients who have failed either one or more TNFI
  • May not be used in combination with other JAK inhibitors, biologics or with azathioprine or cyclosporine 
  • Avoid use in patients with lymphopenia (absolute lymphs <500), neutropenia (ANC <1000) or anemia (Hgb < 8.0) - thus patient should be monitored with CBC and lipid levels as well.
  • Warnings: caution in patients at risk or with a history of gastrointestinal perforations 
  • Renal: baricitinib is not recommended with moderate or severe renal impairment. Renal function may affect baricitinib exposure; thus it is not recommended for use in patients with estimated GFR of less than 60 mL/min/1.73 m2
  • Liver: baricitinib is not recommended in patients with severe hepatic impairment
  • Cancer risk: in the 52 week studies the risk of malignancies (excluding NMSC) was 0.6-0.7  per 100 patient-years for the 2 mg and 4 mg dose groups. 
  • Do not use live vaccinations with baricitinib.
  • Herpes zoster risk was 1-1.4% in patients taking either 2mg or 4mg baricitinib.
  • The effects of baricitinib on patient with hepatitis B or hepatitis C is unknown (such patients were excluded from trials)
  • Opportunistic infections: the risk of TB is 1 in 1000 patient-years. The risk of other opportunistic infections is very low (zero at the 2mg dose and 0.7 per 100 patient-years with baricitinib 4 mg)
  • Interactions: do not take with strong Organic Anion Transporter 3 (OAT3) inhibitors (e.g., probenecid)

This is the second JAK inhibitor to be FDA approved and will likely be used in the same manner and with the same expectations as tofacitinib.  However, some key differences would include: a) baricitinib is only indicated after an inadequate response to TNFi (not so with tofacitinib); b) there is no label or known substantial risk for VTE with tofacitinib; and c) tofacitinib is recommende at a lower dose with moderate to severe renal impairment (baricitinib is not recommended here).

Both drugs have been rarely reported to increase Creatine Phosphokinase (CPK) levels without overt myositis.



The author has received compensation as an advisor or consultant on this subject

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