Olumiant (Baricitinib)
Approved Indications & Off-Label Uses
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Rheumatoid arthritis (RA) | Adults with moderately to severely active RA, inadequate response to ≥1 TNF blocker | Monotherapy or with MTX/non-biologic DMARDs | FDA Approved |
| COVID-19 (hospitalized) | Adults requiring O2, non-invasive/invasive MV, or ECMO | Oral, alone or with other therapies | FDA Approved |
| Alopecia areata (AA) | Adults with severe AA | Monotherapy | FDA Approved |
Baricitinib is a selective oral JAK1/JAK2 inhibitor and the first systemic drug FDA-approved specifically for severe alopecia areata (June 2022). In RA, it is positioned after TNF blocker failure, similar to other JAK inhibitors. For COVID-19, it was initially authorised under EUA and received full approval in May 2022. Unlike tocilizumab and sarilumab, baricitinib offers the convenience of oral daily dosing without infusion or injection. The FDA labelling carries the JAK inhibitor class-wide boxed warning based on the ORAL Surveillance trial (tofacitinib), reflecting elevated risks of MACE, malignancy, thrombosis, and mortality observed with that agent versus TNF blockers in RA patients aged 50 and older with cardiovascular risk factors.
Atopic dermatitis: Approved by EMA but not FDA for moderate-to-severe AD in adults. Evidence quality: High (multiple Phase III trials).
Juvenile idiopathic arthritis: Approved by EMA for active JIA in patients ≥2 years. Not FDA-approved for this indication. Evidence quality: High.
COVID-19 (pediatric, 2–17 yr): Available under EUA for hospitalised paediatric patients requiring O2/MV/ECMO. Evidence quality: Moderate (extrapolated from adult data).
Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| RA — after TNF blocker failure, with or without MTX/cDMARDs | 2 mg PO once daily | 2 mg PO once daily | 2 mg once daily | With or without food Not recommended with biologic DMARDs, other JAK inhibitors, azathioprine, or cyclosporine |
| RA — moderate renal impairment (eGFR 30–60) | 1 mg PO once daily | 1 mg PO once daily | 1 mg once daily | Not recommended if eGFR <30 Mild renal impairment (eGFR 60–90): no adjustment needed |
| COVID-19 — hospitalized, requiring O2/MV/ECMO | 4 mg PO once daily | 4 mg PO once daily × 14 days or until discharge | 4 mg once daily | Can disperse in water or give via NG/G tube Reduce to 2 mg if eGFR 30–60; 1 mg if eGFR 15–30; not recommended if <15 or on dialysis |
| Alopecia areata — initial therapy for severe AA | 2 mg PO once daily | Increase to 4 mg if inadequate response; reduce back to 2 mg once adequate | 4 mg once daily | Consider starting at 4 mg for near-complete or complete scalp hair loss Not recommended with biologic immunomodulators, other JAK inhibitors, cyclosporine, or potent immunosuppressants |
| AA — moderate renal impairment (eGFR 30–60) | 1 mg PO once daily (if 2 mg recommended) or 2 mg PO once daily (if 4 mg recommended) | Per above | 2 mg once daily | Not recommended if eGFR <30 |
| Any indication — with strong OAT3 inhibitor (e.g. probenecid) | Halve the recommended dose | Per halved dose | Per halved dose | Probenecid doubles baricitinib AUC via OAT3 inhibition If recommended dose is 1 mg, consider discontinuing probenecid instead |
Initiation Thresholds
| Parameter | RA / Alopecia Areata | COVID-19 | Action if Below Threshold |
|---|---|---|---|
| Absolute Lymphocyte Count (ALC) | ≥500 cells/mm³ | ≥200 cells/mm³ | Interrupt until threshold met |
| Absolute Neutrophil Count (ANC) | ≥1000 cells/mm³ | ≥500 cells/mm³ | Interrupt until threshold met |
| Haemoglobin | ≥8 g/dL | Limited data if <8 g/dL | Interrupt until ≥8 g/dL (RA/AA) |
Baricitinib is the only JAK inhibitor approved in the US at a 2 mg dose for RA (tofacitinib uses 5 mg BID, upadacitinib 15 mg daily). The FDA approved only the 2 mg dose for RA (not the 4 mg studied in some trials), partly due to thrombosis concerns. The 4 mg dose is reserved for COVID-19 and as a dose-escalation option in alopecia areata. Unlike biologic DMARDs, baricitinib offers oral dosing, rapid onset (ACR20 improvement seen as early as 1 week), and no immunogenicity concerns. However, the JAK class-wide boxed warning requires a thorough risk-benefit discussion, particularly regarding MACE, VTE, and malignancy risk.
Pharmacology
Mechanism of Action
Baricitinib is a small-molecule, selective, reversible inhibitor of Janus kinases JAK1 and JAK2, with lower potency against JAK3 and TYK2. JAK1/JAK2 mediate the intracellular signalling of numerous cytokines, interferons, and growth factors involved in immune cell function, haematopoiesis, and inflammation. By inhibiting JAK1/JAK2 autophosphorylation, baricitinib prevents the phosphorylation and activation of STATs (Signal Transducers and Activators of Transcription), thereby blocking the transcription of pro-inflammatory genes. In RA, this translates to rapid suppression of CRP and ESR within the first week of treatment. In alopecia areata, baricitinib interrupts the IFN-gamma and IL-15 signalling that drives autoimmune attack on hair follicles. In COVID-19, baricitinib provides dual anti-inflammatory (cytokine storm suppression) and potential antiviral effects by inhibiting AP2-associated kinase 1 (AAK1), which facilitates viral endocytosis.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Oral bioavailability ~80%; Tmax ~1 hour; dose-proportional PK. Food has no clinically relevant effect. | Rapid absorption enables fast onset of action. Can be taken with or without food. Tablets can be dispersed in water for patients unable to swallow (COVID-19 ICU setting). |
| Distribution | Vd: ~76 L; plasma protein binding ~50% | Large Vd suggests distribution into tissues beyond the vascular compartment. Moderate protein binding means low risk of displacement interactions. |
| Metabolism | Only ~6% metabolised, primarily by CYP3A4. Not an inhibitor or inducer of CYP450 enzymes or major drug transporters at clinical doses. | Minimal hepatic metabolism means CYP inhibitors/inducers (ketoconazole, rifampicin) have no clinically meaningful effect on baricitinib PK. The main interaction is via OAT3 transport (probenecid). |
| Elimination | t½: ~12.5 hours; ~75% excreted in urine (~69% unchanged), ~20% in faeces. Oral CL: ~17 L/h; renal CL: ~2 L/h. Steady state in 2–3 days. | Predominantly renal elimination of unchanged drug explains the need for dose reduction with renal impairment. Short half-life means >90% eliminated within 24 hours (relevant for overdose management). Minimal accumulation with daily dosing. |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Upper respiratory tract infections | 16.3% (2 mg RA) vs 11.7% placebo | Includes nasopharyngitis, sinusitis, pharyngitis, laryngitis, tonsillitis, and URTI NOS. Most common adverse reaction across all indications. |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 2.7% (2 mg RA) vs 1.6% placebo | Usually mild; does not typically require discontinuation |
| Herpes zoster | 1.0% (2 mg RA) vs 0.4% placebo; IR 3.0/100 pt-yr (all-bari-RA) | JAK class effect; higher in Asian patients and those ≥50 years. Interrupt baricitinib until episode resolves. |
| Herpes simplex | 0.8% (2 mg RA) vs 0.7% placebo | Includes oral herpes, genital herpes, and eczema herpeticum |
| Headache | ≥1% (AA trials) | More notable in alopecia areata population |
| Acne | ≥1% (AA trials) | Reported predominantly in alopecia areata trials |
| Hyperlipidaemia | ≥1% (AA trials) | Increases in total cholesterol, LDL, and HDL observed; manage per lipid guidelines |
| CPK elevation | ≥1% (AA/COVID-19 trials) | Usually asymptomatic; not associated with rhabdomyolysis in trials |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (pneumonia, herpes zoster, UTI) | 3.6 per 100 pt-yr (2 mg); 4.2 placebo | Any time during therapy | Interrupt baricitinib until infection controlled; initiate appropriate antimicrobials |
| Venous thromboembolism (DVT/PE) | IR 0.5/100 pt-yr (all-bari-RA) | Variable | Discontinue baricitinib; evaluate and treat promptly. Avoid in patients at increased thrombosis risk. |
| Major adverse cardiovascular events (MACE) | IR 0.5/100 pt-yr (all-bari-RA); IR 0.77 in patients ≥50 with ≥1 CV risk factor | Variable | Discontinue baricitinib if MI or stroke occurs. Consider risk-benefit in patients with CV risk factors, current/past smokers. |
| Malignancy (excluding NMSC) | IR 1.0/100 pt-yr (52-wk); SIR 1.07 vs general population | Variable; monitored over years | Consider risk-benefit, especially in current/past smokers. Periodic skin examination for NMSC. |
| All-cause mortality | IR 0.33/100 pt-yr (all-bari-RA) | Variable | Class-wide concern based on ORAL Surveillance (tofacitinib). Consider risk-benefit before initiating. |
| GI perforation | IR 0.05/100 pt-yr (all-bari-RA) | Variable | Evaluate promptly for new abdominal symptoms, especially with diverticular disease history |
| Hypersensitivity (angioedema, urticaria, rash) | Post-marketing reports | Variable | Discontinue baricitinib if serious reaction occurs |
Herpes zoster is a JAK class effect that occurs at a consistently higher rate with baricitinib than placebo (IR 3.0/100 pt-yr in all-bari-RA). Risk is highest in patients aged 50 and older, those of Asian descent, and those receiving concurrent glucocorticoids. Most cases are non-serious (mild 40%, moderate 55%) and involve a single dermatome. Interrupt baricitinib until the herpes zoster episode resolves. Shingrix (recombinant zoster vaccine) can be given before or during baricitinib therapy as it is a non-live vaccine.
Drug Interactions
Baricitinib has a favourable drug interaction profile for a small molecule. Only ~6% undergoes CYP3A4 metabolism, and it is neither an inhibitor nor inducer of CYP450 enzymes at clinical doses. The clinically relevant interaction is via the renal organic anion transporter 3 (OAT3), which mediates baricitinib’s active renal secretion.
Monitoring
- CBC (ANC, ALC, Hgb)Baseline; routine monitoring thereafter
RoutineDo not initiate if ALC <500 (RA/AA) or <200 (COVID-19), ANC <1000 (RA/AA) or <500 (COVID-19), Hgb <8 g/dL. Interrupt and resume when thresholds met. - Hepatic Function (ALT, AST)Baseline; routine monitoring
RoutineInterrupt if ALT/AST elevation and DILI suspected, until diagnosis excluded. Not recommended in severe hepatic impairment. - Renal Function (eGFR)Baseline; periodically
RoutineDose adjust for moderate renal impairment (eGFR 30–60). Not recommended if eGFR <30 (RA/AA) or <15 (COVID-19). - Lipid Panel~12 weeks after initiation (RA/AA)
RoutineIncreases in total cholesterol, LDL, and HDL expected. Manage per cardiovascular risk guidelines. - TB ScreeningBaseline (RA/AA); not required for COVID-19
RoutineTest for latent TB before initiating in RA/AA. Treat latent TB before starting baricitinib. Monitor for active TB during treatment. - Viral Hepatitis ScreeningBaseline, per clinical guidelines
RoutineScreen for hepatitis B and C before starting. Monitor HBV DNA in patients who are anti-HBc+/HBsAg−. Consult hepatology if HBV DNA detected. - Signs of ThrombosisOngoing clinical assessment
Trigger-basedDVT, PE, and arterial thrombosis reported. Educate patients on symptoms. Discontinue baricitinib if clinical features of thrombosis occur. - Skin ExaminationPeriodic
Trigger-basedNMSCs reported. Periodic skin cancer screening recommended, especially in patients at increased risk.
Contraindications & Cautions
Absolute Contraindications
- None listed in the FDA PI — Section 4 states “None”
Relative Contraindications (Specialist Input Recommended)
- Active, serious infection including localised infections — avoid use; interrupt if infection develops
- Active tuberculosis — do not administer; test for latent TB (except COVID-19)
- Patients at increased thrombosis risk — avoid baricitinib due to DVT/PE/arterial thrombosis risk
- Patients ≥50 with ≥1 CV risk factor — heightened MACE and mortality concern (JAK class warning)
- Current or past smokers — additional increased risk of malignancy per class labelling
- Severe hepatic impairment (RA/AA) — not recommended
- Severe renal impairment (eGFR <30) (RA/AA) — not recommended
Use with Caution
- History of diverticulitis — increased GI perforation risk
- Chronic or recurrent infection
- Pregnancy — animal data show embryo-fetal toxicity at ≥20× MRHD; advise contraception
Patients treated with baricitinib are at risk for serious infections that may lead to hospitalisation or death, including TB, invasive fungal, bacterial, and viral infections. Based on a large postmarketing safety study of another JAK inhibitor (tofacitinib) in RA patients ≥50 years with ≥1 cardiovascular risk factor, higher rates of all-cause mortality (including sudden CV death), malignancies (lymphoma, lung cancer), MACE (CV death, MI, stroke), and thrombosis (DVT, PE) were observed compared with TNF blockers. Current or past smokers are at additional increased risk. Consider the benefits and risks before initiating or continuing baricitinib, particularly in these higher-risk populations.
Patient Counselling
Purpose of Therapy
Baricitinib works by blocking specific enzymes (JAK1 and JAK2) inside immune cells that drive inflammation. By reducing this inflammation, it helps control symptoms of rheumatoid arthritis, promotes hair regrowth in alopecia areata, and helps the immune system respond more appropriately during severe COVID-19. It is taken as a tablet once daily.
How to Take
Take one tablet daily with or without food, at approximately the same time each day. Swallow whole; if you cannot swallow tablets, they can be dissolved in about 10 mL of room temperature water and drunk immediately. Do not receive live vaccines while taking this medicine.
Sources
- OLUMIANT (baricitinib) tablets, for oral use. Full Prescribing Information. Eli Lilly and Company. Revised 06/2022. FDA LabelPrimary source for all approved indications (RA, COVID-19, AA), dosing, boxed warnings, adverse reactions, PK, and drug interactions.
- European Medicines Agency. Olumiant (baricitinib) Summary of Product Characteristics. EMAEU regulatory reference covering additional indications (atopic dermatitis, JIA) not yet FDA-approved.
- Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis (RA-BEAM). N Engl J Med. 2017;376(7):652-662. doi:10.1056/NEJMoa1608345Pivotal RA trial (n=1305) demonstrating baricitinib 4 mg superiority over adalimumab for ACR20 and DAS28-CRP at 12 weeks (note: 4 mg dose not approved for RA in the US).
- Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis (RA-BEACON). N Engl J Med. 2016;374(13):1243-1252. doi:10.1056/NEJMoa1507247Phase III trial in bDMARD-IR patients (n=527) demonstrating significant ACR20 response with baricitinib vs placebo at week 12.
- Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19 (ACTT-2). N Engl J Med. 2021;384(9):795-807. doi:10.1056/NEJMoa2031994ACTT-2 trial (n=1033) showing baricitinib + remdesivir reduced recovery time vs remdesivir alone (7 vs 8 days) in hospitalised COVID-19 patients.
- Marconi VC, Ramanan AV, de Bono S, et al. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER). Lancet Respir Med. 2021;9(12):1407-1418. doi:10.1016/S2213-2600(21)00331-3COV-BARRIER trial (n=1525) demonstrating 38.2% reduction in 28-day all-cause mortality with baricitinib vs placebo.
- King B, Ohyama M, Kwon O, et al. Two Phase 3 trials of baricitinib for alopecia areata (BRAVE-AA1 and BRAVE-AA2). N Engl J Med. 2022;386(18):1687-1699. doi:10.1056/NEJMoa2110343Twin Phase III trials (n=1200) establishing baricitinib as first FDA-approved systemic treatment for severe AA; 35% achieved ≥80% scalp hair coverage at 36 weeks with 4 mg.
- Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924-939. doi:10.1002/acr.24596Positions JAK inhibitors as an option after cDMARD failure but conditionally recommends TNF inhibitors first due to longer-term safety data.
- Fridman JS, Scherle PA, Collins R, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 2010;184(9):5298-5307. doi:10.4049/jimmunol.0902819Foundational preclinical study establishing baricitinib’s JAK1/JAK2 selectivity profile and anti-inflammatory activity in rodent arthritis models.
- Shi JG, Chen X, Lee F, et al. The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers. J Clin Pharmacol. 2014;54(12):1354-1361. doi:10.1002/jcph.354Phase I PK study establishing dose-linear PK, Tmax ~1.5 h, oral CL 17 L/h, renal CL ~2 L/h, and reversible dose-dependent ANC decline.
- Smolen JS, Genovese MC, Takeuchi T, et al. Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. J Rheumatol. 2019;46(1):7-18. doi:10.3899/jrheum.171361Integrated safety analysis (n=3492, 6637 pt-yr) establishing long-term safety profile including herpes zoster IR 3.2/100 pt-yr, DVT/PE IR 0.5/100 pt-yr.
- Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis (ORAL Surveillance). N Engl J Med. 2022;386(4):316-326. doi:10.1056/NEJMoa2109927Tofacitinib postmarketing study (n=4362) that prompted the JAK class-wide boxed warning regarding MACE, malignancy, thrombosis, and mortality vs TNF blockers.