Baricitinib

Last updated

Baricitinib
Baricitinib structure.svg Baricitinib-portrait-ligand-3JW-from-PDB-xtal-4W9X-Mercury-3D-balls.png
Clinical data
Trade names Olumiant, others
Other namesINCB28050, LY3009104
AHFS/Drugs.com Monograph
MedlinePlus a618033
License data
Pregnancy
category
  • AU:D [1] [2]
  • Use is contraindicated
Routes of
administration
By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 79%
Protein binding 50%
Metabolism CYP3A4 (<10%)
Elimination half-life 12.5 hours
Excretion 75% urine, 20% faeces
Identifiers
  • 2-[1-Ethylsulfonyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.219.080 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C16H17N7O2S
Molar mass 371.42 g·mol−1
3D model (JSmol)
  • CCS(=O)(=O)N1CC(CC#N)(n2cc(-c3ncnc4[nH]ccc34)cn2)C1
  • InChI=1S/C16H17N7O2S/c1-2-26(24,25)22-9-16(10-22,4-5-17)23-8-12(7-21-23)14-13-3-6-18-15(13)20-11-19-14/h3,6-8,11H,2,4,9-10H2,1H3,(H,18,19,20)
  • Key:XUZMWHLSFXCVMG-UHFFFAOYSA-N

Baricitinib, sold under the brand name Olumiant among others, is an immunomodulatory medication used for the treatment of rheumatoid arthritis, alopecia areata, and COVID-19. [6] [7] [8] [9] It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2. [10]

Contents

Baricitinib is approved for medical use in the European Union [7] and in the United States. [8] [11] [9]

Medical uses

In February 2017, baricitinib was approved for use in the European Union as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate. [12] [7]

In May 2018, the US Food and Drug Administration (FDA) approved baricitinib for the treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. [11] [8] [6]

In May 2022, the FDA approved baricitinib for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). [6] [13] [14] baricitinib is the first immunomodulatory treatment for COVID-19 to receive FDA approval. [14]

In the United States, baricitinib is authorized under an emergency use authorization (EUA) for the treatment of COVID-19 in hospitalized people aged 2 to less than 18 years of age who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation. [13]

In June 2022, the FDA authorized baricitinib for the treatment of severe alopecia areata. [9] [15]

Contraindications

During pregnancy, the use of baricitinib is contraindicated. [2] [12]

Side effects

In studies, upper respiratory tract infections and high blood cholesterol levels (hypercholesterolemia) occurred in more than 10% of participants. Less common side effects included other infections such as herpes zoster, herpes simplex, urinary tract infections, and gastroenteritis. [12]

Interactions

Being metabolized only to a small extent, the substance has a low potential for interactions. In studies, inhibitors of the liver enzymes CYP3A4, CYP2C19, and CYP2C9, as well as the CYP3A4 inducer rifampicin, had no relevant influence on baricitinib concentrations in the bloodstream. While baricitinib blocks a number of transporter proteins in vitro , clinically relevant interactions via this mechanism are considered very unlikely, except perhaps for the cation transporter SLC22A1 (OCT1). [12]

An additive effect with other immunosuppressants cannot be excluded. [12]

Pharmacology

Mechanism of action

Baricitinib is a Janus kinase (JAK) inhibitor that reversibly inhibits Janus kinase 1 with a half maximal inhibitory concentration (IC50) of 5.9  nM and Janus kinase 2 with an IC50 of 5.7 nM. Tyrosine kinase 2, which belongs to the same enzyme family, is affected less (IC50 = 53 nM), and Janus kinase 3 far less (IC50 > 400 nM). Via a signal transduction pathway involving STAT proteins, this ultimately modulates gene expression in immunological cells. [12]

Other JAK inhibitors include tofacitinib, which is indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis; [16] [17] fedratinib, [18] and ruxolitinib. [19] [20]

Pharmacokinetics

The substance is quickly absorbed from the gut with an absolute bioavailability of 79%. It reaches highest blood plasma levels after about an hour; in different individuals the time to reach this level ranges from 0.5 to 3 hours. Food intake has no relevant influence on the drug's pharmacokinetics. 50% of the circulating baricitinib are bound to blood plasma proteins. [12]

Less than 10% of the substance is metabolized to four different oxidation products by CYP3A4; the rest is left unchanged. Elimination half-life is 12.5 hours on average. About 75% is eliminated via the urine, and 20% via the faeces. [12]

History

Baricitinib was discovered by Incyte and licensed to Eli Lilly. [21]

Society and culture

In January 2016, Eli Lilly submitted a new drug application to the US Food and Drug Administration (FDA) for the approval of baricitinib to treat moderately-to-severely active rheumatoid arthritis. [22]

In December 2016, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of baricitinib as a therapy for rheumatoid arthritis. [10] European Union approval was granted in February 2017. [7]

Despite widespread expectations that the FDA would approve baricitinib for rheumatoid arthritis, [23] in April 2017, the FDA issued a rejection, citing concerns about dosing and safety. [24] [25]

In May 2018, baricitinib was approved in the United States for the treatment of rheumatoid arthritis. [8] [11] [9]

In March 2020, the US FDA granted breakthrough therapy designation to baricitinib for the treatment of alopecia areata [26] and granted approval in June 2022. [15]

The efficacy and safety of baricitinib in alopecia areata was studied in two randomized, double-blind, placebo-controlled trials (Trial AA-1 and Trial AA-2) with participants who had at least 50% scalp hair loss as measured by the Severity of Alopecia Tool for more than six months. [9] Participants in these trials received either a placebo, 2 milligrams of baricitinib, or 4 milligrams of baricitinib every day. [9] The primary measurement of efficacy for both trials was the proportion of participants who achieved at least 80% scalp hair coverage at week 36. [9]

Research

As of August 2016, 31 clinical trials had been registered for baricitinib of which 24 had completed, [27] and 4 of 6 phase 3 trials had completed. [28] [ needs update ]

As of March 2022, a phase III clinical trial showed hair regrowth for those with alopecia areata. [29]

COVID-19

In April 2020, Lilly announced they were investigating the use of baricitinib for treating people with COVID-19. The drug's anti-inflammatory activity was expected to act on the inflammatory cascade associated with COVID-19. [30] [31]

In April and June 2020, the first two studies of baricitinib prescribed for hospitalized people with COVID-19 were published online. [32] [33] Then in November 2020, published research showed baricitinib was beneficial in treating people with COVID-19. According to the paper "mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication and the cytokine storm, and is associated with beneficial outcomes including in severely ill elderly people". [34]

In a clinical trial of hospitalized people with COVID-19, baricitinib, in combination with remdesivir, was shown to reduce time to recovery within 29 days after initiating treatment compared to participants who received a placebo with remdesivir. [35]

The data supporting the US Food and Drug Administration (FDA) emergency use authorization (EUA) for baricitinib combined with remdesivir was based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), which was conducted by the US National Institute of Allergy and Infectious Diseases (NIAID). [36] [37] This clinical trial evaluated whether baricitinib impacted how long it took for subjects who were also taking remdesivir to recover from COVID-19. [36] The trial followed participants for 29 days and included 1,033 participants with moderate or severe COVID-19; 515 participants received baricitinib plus remdesivir, and 518 participants received placebo plus remdesivir. [36] Recovery was defined as either being discharged from the hospital or being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. [36] The median time to recovery from COVID-19 was seven days for baricitinib plus remdesivir and eight days for placebo plus remdesivir. [36] The odds of a patient's condition progressing to death or being ventilated at day 29 was 31% lower in the baricitinib plus remdesivir group versus the placebo plus remdesivir group. [36] The odds of clinical improvement at day 15 was 30% higher in the baricitinib plus remdesivir group versus the placebo plus remdesivir group. [36] For all of these endpoints, the effects were statistically significant. [36] The EUA was issued to Eli Lilly and Company. [36]

In November 2020, the World Health Organization (WHO) updated its guideline on therapeutics for COVID-19 to include a conditional recommendation against the use of remdesivir, triggered by results from the WHO Solidarity trial. [38] [39]

In November 2020, the FDA issued an emergency use authorization (EUA) for the combination of baricitinib with remdesivir, for the treatment of suspected or laboratory confirmed COVID-19 in hospitalized people aged two years of age or older requiring supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). [40] [41] [36]

Then in September 2021, the largest randomized, placebo-controlled trial of hospitalized people with COVID-19 to date, COV-BARRIER, was published. [42] This trial randomized 1525 participants to either baricitinib or placebo. Nearly 80% of participants were receiving systemic corticosteroids at enrollment. There was an absolute risk reduction of 2.7 percent in the primary endpoint of progression to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28. The 38.2% statistically significant reduction in all-cause 28-day mortality for participants receiving baricitinib compared to placebo was the largest mortality reduction to date and maintained at 60 days. This translates into one additional death prevented for every 20 participants treated with baricitinib. The frequencies of serious adverse events were lower for participants receiving baricitinib compared to those receiving placebo.[ citation needed ]

As of April 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) is evaluating the use of baricitinib to include treatment of COVID-19 in hospitalized people from ten years of age who require supplemental oxygen. [43]

In July 2021, the FDA revised the EUA for baricitinib authorizing it alone for the treatment of COVID-19 in hospitalized people aged two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). [40] [41] [44] Under the revised EUA, baricitinib is not required to be administered with remdesivir. [44]

As of January 2022, the World Health Organization recommends baricitinib for people with severe or critical COVID-19. [45] Thereafter in February 2022, an exploratory randomized, placebo-controlled trial of participants receiving invasive mechanical ventilation or extracorporeal membrane oxygenation were randomly to baricitinib or placebo. There was a 46% statistically significant relative reduction in all-cause mortality for participants receiving baricitinib compared to those receiving placebo at 28 days which was sustained at 60 days. [46]

Then in May 2022, the FDA approved use of baricitinib for the treatment of adults hospitalized with COVID-19 who require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation with a recommended dose of 4 mg once daily for 14 days or until hospital discharge, whichever happens first. [47]

In March 2022, the RECOVERY trial reported that the use of baricitinib cut the risk of death by about a fifth in about 12,000 participants. [48] [49] [50]

Related Research Articles

<span class="mw-page-title-main">Alopecia areata</span> Medical condition

Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. It often results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are possible factors in bringing on alopecia areata in individuals at risk, but in most cases there is no obvious trigger. People are generally otherwise healthy. In a few cases, all the hair on the scalp is lost, or all body hair is lost. Hair loss can be permanent, or temporary.

Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID‑19. It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.

A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes, thereby interfering with the JAK-STAT signaling pathway in lymphocytes.

<span class="mw-page-title-main">Tofacitinib</span> Medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.

<span class="mw-page-title-main">Fostamatinib</span> Chemical compound

Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth.

<span class="mw-page-title-main">Incyte</span> American pharmaceutical company

Incyte Corporation is an American multinational pharmaceutical company with headquarters in Wilmington, Delaware, and Morges, Switzerland. The company was created in 2002 through the merger of Incyte Pharmaceuticals, founded in Palo Alto, California in 1991 and Incyte Genomics, Inc. of Delaware. The company currently operates manufacturing and R&D locations in North America, Europe, and Asia.

<span class="mw-page-title-main">Filgotinib</span> Chemical compound

Filgotinib, sold under the brand name Jyseleca, is a medication used for the treatment of rheumatoid arthritis (RA). It was developed by the Belgian-Dutch biotech company Galapagos NV.

<span class="mw-page-title-main">Remdesivir</span> Antiviral drug

Remdesivir, sold under the brand name Veklury, is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences. It is administered via injection into a vein. During the COVID‑19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in numerous countries.

<span class="mw-page-title-main">Upadacitinib</span> Chemical compound (medication)

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

<span class="mw-page-title-main">COVID-19 drug repurposing research</span> Drug repurposing research related to COVID-19

Drug repositioning is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed. This is one line of scientific research which is being pursued to develop safe and effective COVID-19 treatments. Other research directions include the development of a COVID-19 vaccine and convalescent plasma transfusion.

<span class="mw-page-title-main">Solidarity trial</span> Accelerated multinational clinical trial program to identify therapies against COVID-19

The Solidarity trial for treatments is a multinational Phase III-IV clinical trial organized by the World Health Organization (WHO) and partners to compare four untested treatments for hospitalized people with severe COVID-19 illness. The trial was announced 18 March 2020, and as of 6 August 2021, 12,000 patients in 30 countries had been recruited to participate in the trial.

<span class="mw-page-title-main">Molnupiravir</span> Antiviral medication

Molnupiravir, sold under the brand name Lagevrio, is an antiviral medication that inhibits the replication of certain RNA viruses. It is used to treat COVID‑19 in those infected by SARS-CoV-2. It is taken by mouth.

The treatment and management of COVID-19 combines both supportive care, which includes treatment to relieve symptoms, fluid therapy, oxygen support as needed, and a growing list of approved medications. Highly effective vaccines have reduced mortality related to SARS-CoV-2; however, for those awaiting vaccination, as well as for the estimated millions of immunocompromised persons who are unlikely to respond robustly to vaccination, treatment remains important. Some people may experience persistent symptoms or disability after recovery from the infection, known as long COVID, but there is still limited information on the best management and rehabilitation for this condition.

<span class="mw-page-title-main">Casirivimab/imdevimab</span> Antiviral combination medication

Casirivimab/imdevimab, sold under the brand name REGEN‑COV among others, is a combination medicine used for the treatment and prevention of COVID‑19. It consists of two human monoclonal antibodies, casirivimab and imdevimab that must be mixed together and administered as an infusion or subcutaneous injection. The combination of two antibodies is intended to prevent mutational escape. It is also available as a co-formulated product. It was developed by the American biotechnology company Regeneron Pharmaceuticals.

Bamlanivimab is a monoclonal antibody developed by AbCellera Biologics and Eli Lilly as a treatment for COVID-19. The medication was granted an emergency use authorization (EUA) by the US Food and Drug Administration (FDA) in November 2020, and the EUA was revoked in April 2021.

Bamlanivimab/etesevimab is a combination of two monoclonal antibodies, bamlanivimab and etesevimab, administered together via intravenous infusion as a treatment for COVID-19. Both types of antibody target the surface spike protein of SARS‑CoV‑2.

<span class="mw-page-title-main">Sotrovimab</span> Monoclonal antibody

Sotrovimab, sold under the brand name Xevudy, is a human neutralizing monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. It was developed by GlaxoSmithKline and Vir Biotechnology, Inc. Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.

<span class="mw-page-title-main">Nirmatrelvir/ritonavir</span> Antiviral combination medication

Nirmatrelvir/ritonavir, sold under the brand name Paxlovid, is a co-packaged medication used as a treatment for COVID‑19. It contains the antiviral medications nirmatrelvir and ritonavir and was developed by Pfizer. Both components are protease inhibitors: nirmatrelvir inhibits SARS-CoV-2 main protease, while ritonavir inhibits HIV-1 protease, and is additionally a strong CYP3A inhibitor. It is taken by mouth.

Bebtelovimab is a monoclonal antibody developed by AbCellera and Eli Lilly as a treatment for COVID-19.

Vilobelimab, sold under the brand name Gohibic, is an investigational medication that is used for the treatment of COVID-19. It is a human-mouse chimeric IgG4 kappa antibody that targets human C5a in plasma.

References

  1. 1 2 "Olumiant Product Information" (PDF). Therapeutic Goods Administration (TGA). Archived from the original on 20 September 2021. Retrieved 12 June 2021.
  2. 1 2 "Baricitinib (Olumiant) Use During Pregnancy". Drugs.com. 8 November 2019. Archived from the original on 26 June 2020. Retrieved 16 March 2020.
  3. "AusPAR: Baricitinib". Therapeutic Goods Administration (TGA). 20 May 2021. Archived from the original on 20 May 2021. Retrieved 11 June 2021.
  4. "Summary Basis of Decision (SBD) for Olumiant". Health Canada . 23 October 2014. Archived from the original on 31 May 2022. Retrieved 29 May 2022.
  5. "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  6. 1 2 3 4 "Olumiant- baricitinib tablet, film coated". DailyMed. 13 November 2019. Archived from the original on 27 September 2020. Retrieved 16 March 2020.
  7. 1 2 3 4 5 "Olumiant EPAR". European Medicines Agency (EMA). 3 December 2019. Archived from the original on 25 August 2021. Retrieved 17 March 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. 1 2 3 4 "Drug Trials Snapshots: Olumiant". U.S. Food and Drug Administration (FDA). 31 May 2018. Archived from the original on 13 December 2019. Retrieved 16 March 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. 1 2 3 4 5 6 7 "FDA Approves First Systemic Treatment for Alopecia Areata". U.S. Food and Drug Administration (FDA) (Press release). 13 June 2022. Archived from the original on 14 June 2022. Retrieved 13 June 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  10. 1 2 "Summary of opinion for Olumiant" (PDF). European Medicines Agency (EMA). 15 December 2016. Archived (PDF) from the original on 15 March 2018. Retrieved 18 December 2016.
  11. 1 2 3 "Drug Approval Package: Olumiant (baricitinib)". U.S. Food and Drug Administration (FDA). 5 July 2018. Archived from the original on 28 April 2020. Retrieved 16 March 2020.
  12. 1 2 3 4 5 6 7 8 "Olumiant: EPAR – Product Information" (PDF). European Medicines Agency. 13 February 2017. Archived (PDF) from the original on 12 July 2018. Retrieved 7 June 2017.
  13. 1 2 "Frequently Asked Questions on Olumiant (Baricitinib) for the Treatment of COVID-19" (PDF). U.S. Food and Drug Administration (FDA). 10 May 2022. Archived from the original on 29 July 2021. Retrieved 10 May 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  14. 1 2 "FDA Roundup: May 10, 2022". U.S. Food and Drug Administration (FDA) (Press release). 10 May 2022. Archived from the original on 10 May 2022. Retrieved 10 May 2022.
  15. 1 2 "FDA Approves Lilly and Incyte's Olumiant (baricitinib) As First and Only Systemic Medicine for Adults with Severe Alopecia Areata" (Press release). Eli Lilly. 13 June 2022. Archived from the original on 14 June 2022. Retrieved 13 June 2022 via PR Newswire.
  16. "Xeljanz- tofacitinib tablet, film coated Xeljanz XR- tofacitinib tablet, film coated, extended release". DailyMed. 20 December 2019. Archived from the original on 30 November 2020. Retrieved 28 April 2020.
  17. "FDA approves Xeljanz for rheumatoid arthritis" (Press release). 6 November 2012. Archived from the original on 2 April 2014. Retrieved 16 December 2019.
  18. "Inrebic- fedratinib hydrochloride capsule". DailyMed. 16 August 2019. Archived from the original on 6 April 2021. Retrieved 28 April 2020.
  19. Mesa RA (June 2010). "Ruxolitinib, a selective JAK1 and JAK2 inhibitor for the treatment of myeloproliferative neoplasms and psoriasis". IDrugs. 13 (6): 394–403. PMID   20506062.
  20. "Jakafi- ruxolitinib tablet". DailyMed. 26 February 2020. Archived from the original on 3 November 2020. Retrieved 28 April 2020.
  21. "FDA Approves Lilly and Incyte's Olumiant (baricitinib) As First and Only Systemic Medicine for Adults with Severe Alopecia Areata". Lilly Investors (Press release). 13 June 2022. Retrieved 23 February 2022.
  22. "Lilly and Incyte Announce Submission of NDA to FDA for Oral Once-Daily Baricitinib for Treatment of Moderate-to-Severe Rheumatoid Arthritis". Drugs.com. 19 January 2016. Archived from the original on 10 April 2021. Retrieved 18 December 2016.
  23. Carroll J (13 April 2017). "We don't know when (exactly) Lilly will announce the FDA's baricitinib decision, but watch out for the looming pricing squabble". Endpoints News. Archived from the original on 25 January 2021. Retrieved 14 April 2017.
  24. Ramsey L (17 April 2017). "The FDA shot down a new rheumatoid arthritis drug — and the companies that make the drug are tumbling". Business Insider. Archived from the original on 11 January 2019. Retrieved 14 April 2017.
  25. Grant C (14 April 2017). "Surprise FDA Rejection Will Sting This Biotech" . The Wall Street Journal. Archived from the original on 11 January 2019. Retrieved 14 April 2017.
  26. "Lilly Receives FDA Breakthrough Therapy Designation for Baricitinib for the Treatment of Alopecia Areata" (Press release). Eli Lilly and Company. 16 March 2020. Archived from the original on 17 March 2020. Retrieved 16 March 2020 via PR Newswire.
  27. "Baricitinib clinical trials". ClinicalTrials.gov. Archived from the original on 4 February 2017. Retrieved 26 July 2017.
  28. "Baricitinib phase 3 clinical trials". ClinicalTrials.gov. Archived from the original on 4 February 2017. Retrieved 26 July 2017.
  29. "Re-growing hair: New trials for alopecia areata treatment are a success - Technology Org". 29 March 2022. Archived from the original on 31 March 2022. Retrieved 30 March 2022.
  30. "Eli Lilly to study baricitinib for Covid-19 treatment". Clinical Trials Arena. 13 April 2020. Archived from the original on 17 August 2021. Retrieved 15 May 2020.
  31. Saber-Ayad M, Hammoudeh S, Abu-Gharbieh E, Hamoudi R, Tarazi H, Al-Tel TH, et al. (July 2021). "Current Status of Baricitinib as a Repurposed Therapy for COVID-19". Pharmaceuticals (Basel, Switzerland). 14 (7): 680. doi: 10.3390/ph14070680 . PMC   8308612 . PMID   34358107.
  32. Cantini F, Niccoli L, Matarrese D, Nicastri E, Stobbione P, Goletti D (August 2021). "Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact". J Infect. 81 (2): 318–356. doi:10.1016/j.jinf.2020.04.017. PMC   7177073 . PMID   32333918.
  33. Titanji BK, Farley MM, Mehta A, Connor-Schuler R, Moanna A, Cribbs SK, et al. (8 April 2021). "Use of Baricitinib in Patients With Moderate to Severe Coronavirus Disease 2019". Clin Infect Dis. 72 (7): 1247–1250. doi:10.1093/cid/ciaa879. PMC   7337637 . PMID   32597466.
  34. Stebbing J, Sánchez Nievas G, Falcone M, Youhanna S, Richardson P, Ottaviani S, et al. (January 2021). "JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality". Science Advances. 7 (1): eabe4724. Bibcode:2021SciA....7.4724S. doi: 10.1126/sciadv.abe4724 . PMC   7775747 . PMID   33187978.
  35. Kalil AC, Patterson TF, Mehta AK, Tomashek KM, Wolfe CR, Ghazaryan V, et al. (4 March 2021). "Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19". N Engl J Med. 384 (9): 795–807. doi:10.1056/NEJMoa2031994. PMC   7745180 . PMID   33306283.
  36. 1 2 3 4 5 6 7 8 9 10 "Coronavirus (COVID-19) Update: FDA Authorizes Drug Combination for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 19 November 2020. Archived from the original on 19 November 2020. Retrieved 19 November 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  37. "Baricitinib Emergency Use Authorization (EUA) Center for Drug Evaluation and Research (CDER) Review" (PDF). U.S. Food and Drug Administration (FDA). November 2020. Archived from the original on 10 March 2021. Retrieved 31 July 2021.
  38. World Health Organization (2021). Therapeutics and COVID-19: living guideline, 6 July 2021 (Report). World Health Organization (WHO). hdl: 10665/342368 . WHO/2019-nCoV/therapeutics/2021.2.
  39. Rochwerg B, Agarwal A, Siemieniuk RA, Agoritsas T, Lamontagne F, Askie L, et al. (September 2020). "A living WHO guideline on drugs for covid-19". BMJ. 370: m3379. doi: 10.1136/bmj.m3379 . PMID   32887691.
  40. 1 2 "Baricitinib Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021. Archived from the original on 12 September 2021. Retrieved 31 July 2021.
  41. 1 2 "Fact Sheet for Baricitinib Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021. Archived from the original on 29 July 2021. Retrieved 31 July 2021.
  42. Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, et al. (December 2021). "Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial". Lancet Respir Med. 9 (12): 1407–1418. doi:10.1016/S2213-2600(21)00331-3. PMC   8409066 . PMID   34480861.
  43. "EMA starts evaluating use of Olumiant in hospitalized COVID-19 patients requiring supplemental oxygen". European Medicines Agency (EMA). 29 April 2021. Archived from the original on 14 June 2022. Retrieved 25 April 2022.
  44. 1 2 "Coronavirus (COVID-19) Update: July 30, 2021". U.S. Food and Drug Administration (FDA) (Press release). 30 July 2021. Archived from the original on 30 July 2021. Retrieved 30 July 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  45. "WHO recommends two new drugs to treat COVID-19" (Press release).
  46. Ely EW, Ramanan AV, Kartman CE, de Bono S, Liao R, Piruzeli ML, et al. (April 2022). "Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial". Lancet Respir Med. 10 (4): 327–336. doi:10.1016/S2213-2600(22)00006-6. PMC   8813065 . PMID   35123660.
  47. "FDA Approves Baricitinib for Certain Adult Patients Hospitalized With COVID-19" (Press release).
  48. "New RECOVERY trial result: baricitinib reduces deaths in patients hospitalised with COVID-19 — RECOVERY Trial". www.recoverytrial.net. Archived from the original on 4 March 2022. Retrieved 5 March 2022.
  49. "Another life-saving Covid drug identified". BBC News. 3 March 2022. Archived from the original on 5 March 2022. Retrieved 5 March 2022.
  50. Horby PW, Emberson JR, Mafham M, Campbell M, Peto L, Pessoa-Amorim G, et al. (RECOVERY Collaborative Group) (July 2022). "Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis". Lancet (preprint). 400 (10349): 359–368. doi:10.1101/2022.03.02.22271623. PMC   9333998 . PMID   35908569. S2CID   247216504.

Further reading