Friday, 22 Jun 2018

You are here

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

Add new comment

More Like This

Seronegative and Seropositive Rheumatoids Respond Equally Well

A cohort study of 241 DMARD-naive rheumatoid arthritis (RA) patients, meeting either 1987 ACR or the 2010 ACR/EULAR  classification criteria for RA, compared the baseline status and long term outcomes of seronegative (SNRA) and seropositive (SPRA).

We Measure What we do in RA, But so What?

We are supposed to treat to a target (T2T) in RA. In other words, measure many components of the disease and its activity and calculate a score and if the patient is not in remission (or a low state if remission is not achievable) we are to make a treatment change.

Does RA kill you? Let me count the ways….and what you can do about it

There were many presentations at EULAR 2018 in Amsterdam about the mortality of RA.

FDA Approves Baricitinib 2 mg for Rheumatoid Arthritis

Today the U.S. Food and Drug Administration approved baricitinib (Oluminant) at the lower dose of 2 mg per day for use in adults with with moderate-to-severe active rheumatoid arthritis (RA) who have had an inadequate response to commonly-used treatments known as TNF inhibitors.

Increased Risk of Depression and Anxiety in Rheumatoid Arthritis

Canadian researchers have analyzed population data and shown that the incidence and prevalence of depression, anxiety  and bipolar disorders are elevated in the rheumatoid arthritis (RA) patients compared to a matched population.