Ruxolitinib

Last updated

Ruxolitinib
Ruxolitinib.svg
Clinical data
Trade names Jakafi, Jakavi, Opzelura
Other namesINCB018424, INC424
AHFS/Drugs.com Monograph
MedlinePlus a612006
License data
Pregnancy
category
Routes of
administration 		By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 95% [10]
Protein binding 97% [10]
Metabolism Liver (mainly CYP3A4-mediated) [10]
Elimination half-life 2.8-3 hours [10]
Excretion Urine (74%), faeces (22%) [10]
Identifiers
  • (3R)-3-Cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]propanenitrile
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
Formula C17H18N6
Molar mass 306.373 g·mol−1
3D model (JSmol)
  • N#CCC(C1CCCC1)n1cc(-c2ncnc3[nH]ccc23)cn1
  • InChI=1S/C17H18N6/c18-7-5-15(12-3-1-2-4-12)23-10-13(9-22-23)16-14-6-8-19-17(14)21-11-20-16/h6,8-12,15H,1-5H2,(H,19,20,21)/t15-/m1/s1 Yes check.svgY
  • Key:HFNKQEVNSGCOJV-OAHLLOKOSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Ruxolitinib, sold under the brand name Jakafi among others, is a medication used for the treatment of intermediate or high-risk myelofibrosis, [6] a type of myeloproliferative neoplasm that affects the bone marrow; [11] [12] polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; [6] [13] and steroid-refractory acute graft-versus-host disease. [6] Ruxolitinib is a Janus kinase inhibitor. [6] It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, [6] and by Novartis elsewhere in the world, under the brand name Jakavi. [14]

Contents

It was approved for medical use in the United States in 2011, [15] and in the European Union in 2012. [8] Ruxolitinib is the first FDA-approved pharmacologic treatment to address repigmentation in vitiligo patients. [16]

The crystal structure of ruxolitinib and of its dihydrate form are known. [17]

Medical uses

In the United States and the European Union, ruxolitinib is indicated for the treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia-vera myelofibrosis, or post-essential thrombocythaemia myelofibrosis. [6] [8] It is also indicated for the treatment of adults with polycythaemia vera who are resistant to or intolerant of hydroxyurea. [8] Ruxolitinib is also indicated for the treatment of steroid-refractory acute graft-versus-host disease in people who are twelve years of age and older, [6] and for the treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in people twelve years of age and older. [6] [8] [18] [19] It is commonly given as an oral tablet.[ citation needed ]

In the United States, ruxolitinib cream is indicated for the topical treatment of mild to moderate atopic dermatitis and vitiligo. [7] In the European Union, ruxolitinib cream is indicated for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age. [9]

Side effects

In myelofibrosis, the most common side effects include thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), neutropenia (low levels of neutrophils), urinary tract infections (infection of the kidney, renal pelvis, ureter, bladder or urethra), bleeding, bruising, weight gain, hypercholesterolaemia (high blood cholesterol levels), dizziness, headache and raised liver enzyme levels. [8]

In polycythaemia vera, the most common side effects include anemia (low red blood cell counts) and thrombocytopenia (low blood platelet count), bleeding, bruising, hypercholesterolaemia (high blood cholesterol levels), hypertriglyceridemia (high blood fat levels), dizziness, raised liver enzyme levels and high blood pressure. [8]

In acute graft-versus-host disease, the most common hematologic adverse reactions include anemia, thrombocytopenia, and neutropenia. [6] The most common nonhematologic adverse reactions include infections and edema. [6]

Immunologic side effects have included herpes zoster (shingles) and case reports of opportunistic infections. [20] Metabolic side effects have included weight gain. Laboratory abnormalities have included alanine transaminase (ALT) abnormalities, aspartate transaminase (AST) abnormalities, and mildly elevated cholesterol levels. [6]

Mechanism of action

Ruxolitinib is a Janus kinase inhibitor (JAK inhibitor) with selectivity for subtypes JAK1 and JAK2. [21] [22] Ruxolitinib inhibits dysregulated JAK signaling associated with myelofibrosis. JAK1 and JAK2 recruit signal transducers and activators of transcription (STATs) to cytokine receptors leading to modulation of gene expression. [6]

History

In March 2012, the phase III Controlled Myelofibrosis Study with Oral JAK Inhibitor-I (COMFORT-I) and COMFORT-II trials showed significant benefits by reducing spleen size and relieving debilitating symptoms. [23] [24] [25] [26]

Society and culture

In November 2011, ruxolitinib was approved by the U.S. Food and Drug Administration (FDA) [15] for the treatment of intermediate or high-risk myelofibrosis based on results of the COMFORT-I and COMFORT-II Trials. [27]

In 2014, it was approved in polycythemia vera when there has been an inadequate response to or intolerance of hydroxyurea, based on the RESPONSE trial. [28] [13]

In May 2019, the indication for ruxolitinib was expanded in the US to include steroid-refractory acute graft-versus-host disease. [29] The indication was further expanded in the US in September 2021, for the treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in people 12 years of age and older. [30]

In September 2021, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States [31] for the treatment of mild to moderate atopic dermatitis (AD). [32] It is the first topical Janus kinase inhibitor approved in the United States. [32]

In July 2022, ruxolitinib cream (sold under the brand name Opzelura) was approved for medical use in the United States for the treatment of vitiligo. [16] [33]

On 23 February 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Opzelura, intended for the treatment of non-segmental vitiligo. [34] The applicant for this medicinal product is Incyte Biosciences Distribution B.V. [34]

Research

It is being investigated for plaque psoriasis, [21] alopecia areata, [35] relapsed diffuse large B-cell lymphoma, and peripheral T-cell lymphoma. [36]

In February 2016, a phase III trial for pancreatic cancer was terminated due to insufficient efficacy. [37]

Eight weeks-treatment with ruxolitinib blunted senescent cell-mediated inhibition of adipogenesis and increased insulin sensitivity in 22-month-old mice. [38]

As of September 2019, a clinical trial is in progress to evaluate "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors". [39] [ full citation needed ][ needs update ]

Related Research Articles

Janus kinase (JAK) is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 and 2, but were ultimately published as "Janus kinase". The name is taken from the two-faced Roman god of beginnings, endings and duality, Janus, because the JAKs possess two near-identical phosphate-transferring domains. One domain exhibits the kinase activity, while the other negatively regulates the kinase activity of the first.

<span class="mw-page-title-main">Vitiligo</span> Skin condition where patches lose pigment

Vitiligo is a chronic autoimmune disorder that causes patches of skin to lose pigment or color. The cause of vitiligo is unknown, but it may be related to immune system changes, genetic factors, stress, or sun exposure. Treatment options include topical medications, light therapy, surgery and cosmetics. The condition can show up on any skin type as a light peachy color and can appear on any place on the body in all sizes. The spots on the skin known as vitiligo are also able to “change” as spots lose and regain pigment; they will stay in relatively the same areas but can move over time and some big patches can move through the years but never disappear overnight.

<span class="mw-page-title-main">Tacrolimus</span> Immunosuppressive drug

Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogenic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs.

<span class="mw-page-title-main">Pimecrolimus</span> Immunosuppressive drug

Pimecrolimus is an immunosuppressant drug of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema).

Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL genes. In PMF, the bony aspects of bone marrow are remodeled in a process called osteosclerosis; in addition, fibroblast secrete collagen and reticulin proteins that are collectively referred to as (fibrosis). These two pathological processes compromise the normal function of bone marrow resulting in decreased production of blood cells such as erythrocytes, granulocytes and megakaryocytes, the latter cells responsible for the production of platelets.

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

Roflumilast, sold under the brand name Daxas among others, is a medication used for the treatment of chronic obstructive pulmonary disease, plaque psoriasis, seborrheic dermatitis, and atopic dermatitis. It acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects.

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">Phosphoinositide 3-kinase inhibitor</span>

Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.

<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">Fedratinib</span> Chemical compound

Fedratinib, sold under the brand name Inrebic, is an anti-cancer medication used to treat myeloproliferative diseases including myelofibrosis. It is used in the form of fedratinib hydrochloride capsules that are taken by mouth. It is a semi-selective inhibitor of Janus kinase 2 (JAK-2). It was approved by the FDA on 16 August 2019.

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

Momelotinib, sold under the brand name Ojjaara among others, is an anticancer medication used for the treatment of myelofibrosis. It is a Janus kinase inhibitor and it is taken by mouth.

<span class="mw-page-title-main">Ibrutinib</span> Medication used in cancer treatment

Ibrutinib, sold under the brand name Imbruvica among others, is a small molecule drug that inhibits B-cell proliferation and survival by irreversibly binding the protein Bruton's tyrosine kinase (BTK). Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Ibrutinib is therefore used to treat such cancers, including mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia. Ibrutinib also binds to C-terminal Src Kinases. These are off-target receptors for the BTK inhibitor. Ibrutinib binds to these receptors and inhibits the kinase from promoting cell differentiation and growth. This leads to many different side effects like left atrial enlargement and atrial fibrillation during the treatment of Chronic Lymphocytic Leukemia.

<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">Baricitinib</span> Chemical compound

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. It acts as an inhibitor of janus kinase (JAK), blocking the subtypes JAK1 and JAK2.

<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">Gandotinib</span> Chemical compound

Gandotinib (LY-2784544) is an experimental drug developed by Eli Lilly for treatment of cancer. It is a small molecule JAK2 inhibitor, with additional minor inhibition of STAT3.

<span class="mw-page-title-main">Upadacitinib</span> Biopharmaceutical drug

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">Belumosudil</span> Chemical compound

Belumosudil, sold under the brand name Rezurock among others, is a medication used for the treatment of chronic graft versus host disease (cGvHD). It is in the class of drugs known as serine/threonine kinase inhibitors. Specifically, it is an inhibitor of Rho-associated coiled-coil kinase 2. ROCK2-mediated signaling pathways are major players in pro- and anti-inflammatory immune cell responses. A study in cultured human cells demonstrated that the drug also has effects on oxidative phosphorylation, WNT signaling, angiogenesis, and KRAS signaling.

<span class="mw-page-title-main">Pemigatinib</span> Pharmaceutical drug

Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.

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

Asciminib, sold under the brand name Scemblix, is a medication used to treat Philadelphia chromosome-positive chronic myeloid leukemia. Asciminib is a protein kinase inhibitor.

References

  1. 1 2 "JAKAVI (Novartis Pharmaceuticals Australia Pty LTD) | Therapeutic Goods Administration (TGA)". Archived from the original on 8 March 2023. Retrieved 8 March 2023.
  2. ↑ "JAKAVI ruxolitinib (as phosphate) 5 mg tablet blister pack (198934)". Therapeutic Goods Administration (TGA). 27 May 2022. Archived from the original on 8 March 2023. Retrieved 12 July 2024.
  3. ↑ "Jakavi Product information". Health Canada . 22 October 2009. Archived from the original on 8 March 2023. Retrieved 7 March 2023.
  4. ↑ "Jakavi 10mg Tablets - Summary of Product Characteristics (SmPC)". (emc). 5 April 2022. Archived from the original on 8 March 2023. Retrieved 7 March 2023.
  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 5 6 7 8 9 10 11 12 13 "Jakafi- ruxolitinib tablet". DailyMed. 26 February 2020. Archived from the original on 3 November 2020. Retrieved 16 November 2020.
  7. 1 2 "Opzelura- ruxolitinib cream". DailyMed. Archived from the original on 1 November 2021. Retrieved 31 October 2021.
  8. 1 2 3 4 5 6 7 "Jakavi EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 12 November 2020. Retrieved 16 November 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. 1 2 "Opzelura EPAR". European Medicines Agency. 20 April 2023. Archived from the original on 24 April 2023. Retrieved 23 April 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. 1 2 3 4 5 "Jakafi (ruxolitinib) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Archived from the original on 12 December 2018. Retrieved 16 February 2014.
  11. ↑ Mesa RA, Yasothan U, Kirkpatrick P (February 2012). "Ruxolitinib". Nature Reviews. Drug Discovery. 11 (2): 103–4. doi:10.1038/nrd3652. PMID   22293561. S2CID   233195859.
  12. ↑ Harrison C, Mesa R, Ross D, Mead A, Keohane C, Gotlib J, et al. (October 2013). "Practical management of patients with myelofibrosis receiving ruxolitinib". Expert Review of Hematology. 6 (5): 511–23. doi:10.1586/17474086.2013.827413. PMC   8201600 . PMID   24083419. S2CID   5470231.
  13. 1 2 Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, et al. (January 2015). "Ruxolitinib versus standard therapy for the treatment of polycythemia vera". The New England Journal of Medicine. 372 (5): 426–35. doi:10.1056/NEJMoa1409002. PMC   4358820 . PMID   25629741.
  14. ↑ "FDA Approves Jakafi® (Ruxolitinib) for the Treatment of Patients with Uncontrolled Polycythemia Vera". 4 December 2014. Archived from the original on 8 March 2023. Retrieved 8 March 2023.
  15. 1 2 "Drug Approval Package: Jakafi (ruxolitinib) Tablets NDA # 202192". Archived from the original on 20 December 2022. Retrieved 20 December 2022.
  16. 1 2 "FDA approves topical treatment". U.S. Food and Drug Administration (FDA) (Press release). 19 July 2022. Archived from the original on 20 December 2022. Retrieved 20 December 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  17. ↑ Peng Z, Ye L (August 2024). "Comparison of the crystal structures of the JAK1/2 inhibitor ruxolitinib and its hydrate and phosphate". Acta Crystallographica Section C. 80 (Pt 8): 440–447. Bibcode:2024AcCrC..80..440P. doi:10.1107/S2053229624006740. PMID   39046815.
  18. ↑ "FDA approves ruxolitinib for chronic graft-versus-host disease". U.S. Food and Drug Administration (FDA). 22 September 2021. Archived from the original on 23 September 2021. Retrieved 22 September 2021.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  19. ↑ "EU Commission Approval" (Press release). Novartis. 5 May 2022. Archived from the original on 6 July 2022. Retrieved 5 July 2022.
  20. ↑ Wysham NG, Sullivan DR, Allada G (May 2013). "An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor". Chest. 143 (5): 1478–1479. doi:10.1378/chest.12-1604. PMC   5991580 . PMID   23648912.
  21. 1 2 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.
  22. ↑ Pardanani A, Tefferi A (March 2011). "Targeting myeloproliferative neoplasms with JAK inhibitors". Current Opinion in Hematology. 18 (2): 105–10. doi:10.1097/MOH.0b013e3283439964. PMID   21245760. S2CID   2059415.
  23. ↑ Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. (March 2012). "JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis". The New England Journal of Medicine. 366 (9): 787–98. doi:10.1056/NEJMoa1110556. hdl: 2158/605459 . PMID   22375970.
  24. ↑ Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. (March 2012). "A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis". The New England Journal of Medicine. 366 (9): 799–807. doi:10.1056/NEJMoa1110557. PMC   4822164 . PMID   22375971.
  25. ↑ Tefferi A (March 2012). "Challenges facing JAK inhibitor therapy for myeloproliferative neoplasms". The New England Journal of Medicine. 366 (9): 844–6. doi:10.1056/NEJMe1115119. PMID   22375977.
  26. ↑ ASCO Annual Meeting 2011: JAK Inhibitor Ruxolitinib Demonstrates Significant Clinical Benefit in Myelofibrosis Archived 21 November 2011 at the Wayback Machine
  27. ↑ "FDA Approves Incyte's Jakafi (ruxolitinib) for Patients with Myelofibrosis" (Press release). Incyte. Archived from the original on 24 June 2017. Retrieved 2 January 2012.
  28. ↑ Kaminskas E (4 December 2014). "Supplemental FDA approval letter for Jakafi (ruxolitinib) tablets" (PDF). U.S. Food and Drug Administration. Archived (PDF) from the original on 11 April 2021. Retrieved 1 May 2016.
  29. ↑ "FDA approves ruxolitinib for acute graft-versus-host disease". U.S. Food and Drug Administration. 24 May 2019. Archived from the original on 20 December 2022. Retrieved 20 December 2022.
  30. ↑ "FDA approves ruxolitinib for chronic graft-versus-host disease". U.S. Food and Drug Administration. 31 January 2022. Archived from the original on 23 September 2021. Retrieved 20 December 2022.
  31. ↑ "Drug Approval Package: OPZELURA". Archived from the original on 20 December 2022. Retrieved 20 December 2022.
  32. 1 2 "Incyte Announces U.S. FDA Approval of Opzelura (ruxolitinib) Cream, a Topical JAK Inhibitor, for the Treatment of Atopic Dermatitis (AD)". Incyte. 21 September 2021. Archived from the original on 22 September 2021. Retrieved 21 September 2021– via Business Wire.
  33. ↑ "Incyte Announces U.S. FDA Approval of Opzelura (ruxolitinib) Cream for the Treatment of Vitiligo". Incyte. 19 July 2022. Archived from the original on 19 July 2022. Retrieved 19 July 2022– via Business Wire.
  34. 1 2 "Opzelura: Pending EC decision". European Medicines Agency (EMA). 24 February 2023. Archived from the original on 24 February 2023. Retrieved 24 February 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  35. ↑ Falto-Aizpurua L, Choudhary S, Tosti A (December 2014). "Emerging treatments in alopecia". Expert Opinion on Emerging Drugs. 19 (4): 545–56. doi:10.1517/14728214.2014.974550. PMID   25330928. S2CID   21604470.
  36. ↑ Clinical trial number NCT01431209 for "Ruxolitinib Phosphate (Oral JAK Inhibitor INCB18424) in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell or Peripheral T-Cell Non-Hodgkin Lymphoma" at ClinicalTrials.gov
  37. ↑ House DW (February 2016). "Incyte bags late-stage development of Jakafi for solid tumors; shares down 10% premarket". Seeking Alpha. Archived from the original on 10 October 2016. Retrieved 11 February 2016.
  38. ↑ Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, et al. (December 2015). "Targeting senescent cells enhances adipogenesis and metabolic function in old age". eLife. 4: e12997. doi: 10.7554/eLife.12997 . PMC   4758946 . PMID   26687007.
  39. ↑ Clinical trial number NCT03610971 for "Treatment Free Remission After Combination Therapy With Ruxolitinib Plus Tyrosine Kinase Inhibitors" at ClinicalTrials.gov
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