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Tofacitinib

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Tofacitinib
Clinical data
Trade namesXeljanz, Jaquinus, Tofacinix, Others
Other namesCP-690550
AHFS/Drugs.comMonograph
MedlinePlusa613025
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classJanus kinase (JAK) inhibitor
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability74%
Protein binding40%
MetabolismLiver (via CYP3A4 and CYP2C19)
Elimination half-life3 hours
ExcretionUrine
Identifiers
  • 3-[(3R,4R)-4-Methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
CAS Number
PubChem CID
PubChem SID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.215.928 Edit this at Wikidata
Chemical and physical data
FormulaC16H20N6O
Molar mass312.377 g·mol−1
3D model (JSmol)
  • CC1CCN(C(=O)CC#N)CC1N(C)c1ncnc2[nH]ccc12
  • InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1
  • Key:UJLAWZDWDVHWOW-YPMHNXCESA-N

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.[8][9][10] It is a janus kinase (JAK) inhibitor,[8][9] discovered and developed by the National Institutes of Health and Pfizer.

Common side effects include diarrhea, headache, and high blood pressure.[10] Serious side effects may include infections, cancer, and pulmonary embolism.[10][11] In 2019, the safety committee of the European Medicines Agency began a review of tofacitinib and recommended that doctors temporarily not prescribe the 10 mg twice-daily dose to people at high risk for pulmonary embolism.[12] The U.S. Food and Drug Administration (FDA) also released warnings about the risk of blood clots.[13][14][15] An important side effect of Jakinibs is serious bacterial, mycobacterial, fungal and viral infections. In the phase III trials of tofacitinib among opportunistic infections, pulmonary tuberculosis (TB) was reported in 3 cases all of which were initially negative upon screening for TB.[16]

It was approved for medical use in the United States in November 2012.[17] The extended release version was approved in February 2016.[18] It is available as a generic medication.[19]

Medical uses

[edit]

Rheumatoid arthritis

[edit]

Tofacitinib citrate is approved for medical use in the United States with an indication "to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to, or who are intolerant of, methotrexate."[20][8]

In the European Union, in combination with methotrexate, tofacitinib citrate is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adults who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs.[9] It can be given as monotherapy in case of intolerance to methotrexate or when treatment with MTX is inappropriate.[9]

Ulcerative colitis

[edit]

In May 2018, the FDA approved tofacitinib citrate "for the treatment of adult patients in the U.S. with moderately to severely active ulcerative colitis."[21] Tofacitinib citrate is the first oral JAK inhibitor approved for use in chronic ulcerative colitis.

Adverse effects

[edit]

Tofacitinib was initially not approved by European regulatory agencies because of concerns over efficacy and safety,[22] although by 2018, the European Commission had approved it.[23] Animal studies with tofacitinib conducted prior to human trials showed some carcinogenesis, mutagenesis, and impairment of fertility.[8]

The most commonly reported adverse reactions during the first three months in controlled clinical trials (occurring in 2% or more of patients treated with tofacitinib citrate monotherapy or in combination with DMARDs) were upper respiratory tract infections, headache, diarrhea, and nasopharyngitis (the "common cold").[8]

Tofacitinib is required by the FDA to have a boxed warning on its label about possible injury and death due to problems such as infections, lymphoma, and other malignancies, which can arise from use of this drug.[20] Serious infections leading to hospitalization or death, including tuberculosis and bacterial, invasive fungal, viral, and other opportunistic infections, have occurred in patients receiving tofacitinib. Epstein Barr virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with tofacitinib while on immunosuppressive medications. Patients are warned to avoid use of tofacitinib citrate during an "active serious infection, including localized infections." Doctors are advised to use it with caution in patients who may be at increased risk of gastrointestinal perforations. Laboratory monitoring is recommended due to potential changes in lymphocytes, neutrophils, hemoglobin, liver enzymes, and lipids. Tofacitinib claims to have no contraindications, but doctors are advised to reduce the patient's dosage when combined with "potent inhibitors of cytochrome P450 3A4 (CYP3A4)," such as ketoconazole, or one or more combined medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 such as fluconazole. Furthermore, immunizations with live vaccines should be avoided by tofacitinib users.[8]

According to postmarketing research, tofacitinib may also increase the risk for pulmonary embolism. Prescribers should consider risk factors for pulmonary embolism, including age, obesity, smoking, and immobilization before prescribing this medication. Patients taking this medication, irrespective of indication or risk factors, should be monitored for signs and symptoms of pulmonary embolism.[24]

Mechanism

[edit]

It is an inhibitor of the enzyme janus kinase 1 (JAK1) and janus kinase 3 (JAK 3), which means that it interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription.[25]

In a mouse model of established arthritis, tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. This efficacy in this disease model correlated with the inhibition of both JAK1 and JAK3 signaling pathways, suggesting that tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3.[26]

History

[edit]

The potential significance of JAK3 inhibition was first discovered in the laboratory of John O'Shea, an immunologist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH).[27] In 1994, Pfizer was approached by the NIH to form a public-private partnership to evaluate and bring to market experimental compounds based on this research.[27] Pfizer initially declined the partnership, but agreed in 1996, after the elimination of an NIH policy dictating that the market price of a product resulting from such a partnership would need to be commensurate with the investment of public taxpayer revenue and the "health and safety needs of the public."[27] Pfizer worked with O'Shea's laboratory to define the structure and function of JAK3 and its receptors, and then handled the drug discovery, preclinical development, and clinical development of tofacitinib in-house.[28]

The drug was coded as CP-690,550[29] during development. Its original recommended International nonproprietary name (rINN) was tasocitinib,[30] but that was overruled during the INN approval process as being not optimally differentiable from other existing INNs, so the name "tofacitinib" was proposed and became the INN.

In November 2012, the FDA approved tofacitinib for treatment of rheumatoid arthritis.[8][17]

A 2014 study showed that tofacitinib treatment was able to convert white fat tissues into more metabolically active brown fat, suggesting it may have potential applications in the treatment of obesity.[31]

In November 2012, the FDA approved tofacitinib to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to, or who are intolerant of, methotrexate.[20] The FDA approved only the five-mg, twice-daily dose on the grounds that a higher dose was not considered to have an adequate risk-to-benefit ratio.[32]

In September 2020, the FDA approved tofacitinib for the treatment of children and adolescents two years of age and older with active polyarticular course juvenile idiopathic arthritis.[33]

In December 2021, the FDA approved tofacitinib for the treatment of adults with active ankylosing spondylitis.[34]

As of June 2021, tofacitinib is available as a generic medicine in the US.[35][36]

Society and culture

[edit]

Names

[edit]

Tofacitinib is marketed as Xeljanz except for Russia, where it is marketed as Jaquinus.[37]

Research

[edit]

As of August 2024, recent research on tofacitinib confirms its effectiveness in treating moderate to severe rheumatoid arthritis and other inflammatory conditions. New studies are exploring its safety profile, expanding indications (such as ankylosing spondylitis and atopic dermatitis), and comparing it with other treatments. Ongoing research also focuses on optimizing dosage and evaluating combination therapies. For the latest findings, consult recent peer-reviewed studies and clinical guidelines.[38]

It has demonstrated effectiveness in the treatment of psoriasis in phase III studies. As of November 2013 it was studied in immunological diseases, as well as for the prevention of organ transplant rejection.[39][40][41][42]

Psoriasis

[edit]

Tofacitinib is an investigational drug in psoriasis. As of October 2015, it demonstrated its effectiveness for plaque psoriasis in phase III, randomized, controlled trials in comparison to placebo and to etanercept.[32][43][44] [45] In particular, a ten-mg, twice-daily dose of tofacitinib was shown to be not inferior to etanercept 50 mg, subcutaneously, twice weekly.[44] In October 2015, the FDA rejected approval of tofacitinib for the treatment of psoriasis due to safety concerns.[46]

Alopecia areata

[edit]

Based on preclinical studies in a mouse model of the disease,[47] tofacitinib has been investigated for the treatment of alopecia areata. Early case reports[48][49] suggested potential efficacy, as did a phase II open-label clinical trial,[50] published in tandem with a phase II clinical trial showing the same for ruxolitinib.[51]

Vitiligo

[edit]

In a June 2015 case report, a 53-year-old woman with vitiligo showed noticeable improvement after taking tofacitinib for five months.[52]

Atopic dermatitis

[edit]

The results of using tofacitinib in six patients with recalcitrant atopic dermatitis was published in September 2015. All saw improvement in their atopic dermatitis without any adverse events.[53]

Ankylosing spondylitis

[edit]

In 2021 and 2022, results of a phase III randomised, double-blind, placebo-controlled trial were reported, that showed significant improvements for patients with active ankylosing spondylitis compared to placebo.[54][55]

Ulcerative colitis

[edit]

As of November 2013, it was studied for treatment of inflammatory bowel disease.[56][45]The FDA approved tofacitinib in May 2018 for treatment of ulcerative colitis.[21]

References

[edit]
  1. ^ "Tofacitinib Use During Pregnancy". Drugs.com. 15 April 2020. Retrieved 23 October 2020.
  2. ^ "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.
  3. ^ "Xeljanz/Xeljanz XR (Pfizer Australia Pty Ltd)". Therapeutic Goods Administration (TGA). 16 February 2023. Retrieved 10 April 2023.
  4. ^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  5. ^ "Product monograph brand safety updates". Health Canada. 6 June 2024. Retrieved 8 June 2024.
  6. ^ "10 mg film-coated tablets - Summary of Product Characteristics (SmPC)". (emc). 13 October 2020. Retrieved 3 November 2020.
  7. ^ "Xeljanz 11 mg prolonged release tablets - Summary of Product Characteristics (SmPC)". (emc). Retrieved 3 November 2020.
  8. ^ a b c d e f g h "Xeljanz- tofacitinib tablet, film coated Xeljanz XR- tofacitinib tablet, film coated, extended release Xeljanz- tofacitinib solution". DailyMed. 2 October 2020. Retrieved 3 November 2020.
  9. ^ a b c d e "Xeljanz EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 3 November 2020. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  10. ^ a b c "Tofacitinib Citrate". The American Society of Health-System Pharmacists. Retrieved 1 June 2018.
  11. ^ "Safety Alerts for Human Medical Products - Xeljanz, Xeljanz XR (tofacitinib): Safety Communication - Safety Trial Finds Increased Risk of Blood Clots in the Lungs and Death with Higher Dose in Rheumatoid Arthritis Patients". U.S. Food and Drug Administration (FDA). Retrieved 2 March 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ^ "Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 13-16 May 2019, May 17, 2019". European Medicines Agency. 17 May 2019. Retrieved 17 May 2019.
  13. ^ "Xeljanz, Xeljanz XR (tofacitinib): Drug Safety Communication - Due to an Increased Risk of Blood Clots and Death with Higher Dose". U.S. Food and Drug Administration (FDA). 26 July 2019. Archived from the original on 15 December 2019. Retrieved 10 August 2019. Public Domain This article incorporates text from this source, which is in the public domain.
  14. ^ FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR). U.S. Food and Drug Administration (FDA) (Podcast). 5 August 2019. Retrieved 15 December 2019.
  15. ^ "FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR)". U.S. Food and Drug Administration. 15 December 2019. Archived from the original on 15 December 2019. Retrieved 15 December 2019.
  16. ^ O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A (April 2013). "Janus kinase inhibitors in autoimmune diseases". Annals of the Rheumatic Diseases. 72 (Suppl 2): ii111–ii115. doi:10.1136/annrheumdis-2012-202576. PMC 3616338. PMID 23532440.
  17. ^ a b "Drug Approval Package: Xeljanz (tofacitinib) Tablets NDA #203214". U.S. Food and Drug Administration (FDA). 28 December 2012. Retrieved 30 June 2023.
  18. ^ "Drug Approval Package: Xeljanz (tofacitinib) Extended Release (XR) Tablets NDA #208246". U.S. Food and Drug Administration (FDA). 26 June 2017. Retrieved 30 June 2023.
  19. ^ "First Generic Drug Approvals 2023". U.S. Food and Drug Administration (FDA). 30 May 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  20. ^ a b c "FDA approves Xeljanz for rheumatoid arthritis". U.S. Food and Drug Administration (FDA) (Press release). 6 November 2012. Archived from the original on 2 April 2014. Public Domain This article incorporates text from this source, which is in the public domain.
  21. ^ a b "FDA approves new treatment for moderately to severely active ulcerative colitis". U.S. Food and Drug Administration (FDA) (Press release). 30 May 2018. Archived from the original on 15 December 2019. Retrieved 1 June 2018. Public Domain This article incorporates text from this source, which is in the public domain.
  22. ^ Nordqvist C (27 April 2013). "Pfizer's Arthritis Drug Xeljanz (tofacitinib) Receives A Negative Opinion In Europe". Medical News Today. Retrieved 2 August 2013.
  23. ^ McKee S (29 June 2018). "EU approves Pfizer's Xeljanz for psoriatic arthritis". PharmaTimes. Retrieved 3 June 2019.
  24. ^ FDA Warns of Risk for PE, Death With Higher Dose Tofacitinib (Xeljanz) for RA - Medscape - 25 February 2019.
  25. ^ Adis Editorial (2010). "Tofacitinib". Drugs in R&D. 10 (4): 271–284. doi:10.2165/11588080-000000000-00000. PMC 3585773. PMID 21171673.
  26. ^ Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. (April 2011). "Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550)". Journal of Immunology. 186 (7): 4234–4243. doi:10.4049/jimmunol.1003668. PMC 3108067. PMID 21383241.
  27. ^ a b c Weisman J (18 March 2013). "Seeking Profit for Taxpayers in Potential of New Drug". New York Times.
  28. ^ Garber K (January 2013). "Pfizer's first-in-class JAK inhibitor pricey for rheumatoid arthritis market". Nature Biotechnology. 31 (1): 3–4. doi:10.1038/nbt0113-3. PMID 23302910. S2CID 33144447.
  29. ^ Kremer JM, Bloom BJ, Breedveld FC, Coombs JH, Fletcher MP, Gruben D, et al. (July 2009). "The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double-blind, placebo-controlled phase IIa trial of three dosage levels of CP-690,550 versus placebo". Arthritis and Rheumatism. 60 (7): 1895–1905. doi:10.1002/art.24567. PMID 19565475.
  30. ^ Herper M (2 March 2011). "Why Pfizer's Biggest Experimental Drug Got A Name Change". Forbes. Retrieved 3 March 2011.
  31. ^ Moisan A, Lee YK, Zhang JD, Hudak CS, Meyer CA, Prummer M, et al. (January 2015). "White-to-brown metabolic conversion of human adipocytes by JAK inhibition". Nature Cell Biology. 17 (1): 57–67. doi:10.1038/ncb3075. PMC 4276482. PMID 25487280.
  32. ^ a b Di Lernia V, Bardazzi F (January 2016). "Profile of tofacitinib citrate and its potential in the treatment of moderate-to-severe chronic plaque psoriasis". Drug Design, Development and Therapy. 10: 533–539. doi:10.2147/DDDT.S82599. PMC 4743637. PMID 26889081.
  33. ^ "U.S. FDA Approves Pfizer's Xeljanz (tofacitinib) for the Treatment of Active Polyarticular Course Juvenile Idiopathic Arthritis". Pfizer (Press release). Retrieved 21 August 2023.
  34. ^ "U.S. FDA Approves Pfizer's Xeljanz (tofacitinib) for the Treatment of Active Ankylosing Spondylitis". Pfizer (Press release). Retrieved 21 August 2023.
  35. ^ "Tofacitinib citrate: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 24 September 2021.
  36. ^ "Tofacitinib: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 24 September 2021.
  37. ^ "Pfizer Provides Update on Global Regulatory Approvals and Launches of Xeljanz (tofacitinib citrate) for the Treatment of Rheumatoid Arthritis". Pfizer (Press release). 15 July 2013. Retrieved 3 November 2020.
  38. ^ "Tofacent 5 mg (Tofacitinib) Tablet - Buy Offer Price". Emergency Drug. 20 April 2024. Retrieved 28 August 2024.
  39. ^ Kirk AD, Knechtle SJ, Larsen CP, Madsen JC, Pearson TC, Webber SA (21 July 2014). Textbook of Organ Transplantation Set. John Wiley & Sons. pp. 245–. ISBN 978-1-118-88962-6.
  40. ^ Wojciechowski D, Vincenti F (September 2013). "Tofacitinib in kidney transplantation". Expert Opinion on Investigational Drugs. 22 (9): 1193–1199. doi:10.1517/13543784.2013.811231. PMID 23841583. S2CID 6768856.
  41. ^ Myrvang H (June 2012). "Transplantation: Tofacitinib safe and effective in renal transplant recipients". Nature Reviews. Nephrology. 8 (8): 432. doi:10.1038/nrneph.2012.120. PMID 22735765. S2CID 9819931.
  42. ^ Kalluri HV, Hardinger KL (August 2012). "Current state of renal transplant immunosuppression: Present and future". World Journal of Transplantation. 2 (4): 51–68. doi:10.5500/WJT.v2.i4.51. PMC 3782235. PMID 24175197.
  43. ^ Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, et al. (October 2015). "Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials". The British Journal of Dermatology. 173 (4): 949–961. doi:10.1111/bjd.14018. PMID 26149717.
  44. ^ a b Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. (August 2015). "Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial". Lancet. 386 (9993): 552–561. doi:10.1016/S0140-6736(14)62113-9. PMID 26051365. S2CID 6087705.
  45. ^ a b Zand MS (July 2013). "Tofacitinab in renal transplantation". Transplantation Reviews. 27 (3): 85–89. doi:10.1016/j.trre.2013.04.001. PMC 3713609. PMID 23849222.
  46. ^ "Pfizer Receives Complete Response Letter from FDA for Oral Xeljanz (tofacitinib citrate) Supplemental New Drug Application for Moderate to Severe Chronic Plaque Psoriasis" (Press release). Pfizer. 14 October 2015.
  47. ^ Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, et al. (September 2014). "Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition". Nature Medicine. 20 (9): 1043–1049. doi:10.1038/nm.3645. PMC 4362521. PMID 25129481.
  48. ^ Craiglow BG, King BA (December 2014). "Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis". The Journal of Investigative Dermatology. 134 (12): 2988–2990. doi:10.1038/jid.2014.260. PMID 24940651.
  49. ^ Jabbari A, Nguyen N, Cerise JE, Ulerio G, de Jong A, Clynes R, et al. (August 2016). "Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers". Experimental Dermatology. 25 (8): 642–643. doi:10.1111/exd.13060. PMC 4963264. PMID 27119625.
  50. ^ Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, et al. (September 2016). "Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata". JCI Insight. 1 (15): e89776. doi:10.1172/jci.insight.89776. PMC 5033755. PMID 27699252.
  51. ^ Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, et al. (September 2016). "Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata". JCI Insight. 1 (15): e89790. doi:10.1172/jci.insight.89790. PMC 5033756. PMID 27699253.
  52. ^ Craiglow BG, King BA (October 2015). "Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy". JAMA Dermatology. 151 (10): 1110–1112. doi:10.1001/jamadermatol.2015.1520. PMID 26107994.
  53. ^ Levy LL, Urban J, King BA (September 2015). "Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate". Journal of the American Academy of Dermatology. 73 (3): 395–399. doi:10.1016/j.jaad.2015.06.045. PMID 26194706.
  54. ^ Deodhar A, Sliwinska-Stanczyk P, Xu H, Baraliakos X, Gensler LS, Fleishaker D, et al. (August 2021). "Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study". Annals of the Rheumatic Diseases. 80 (8): 1004–1013. doi:10.1136/annrheumdis-2020-219601. PMC 8292568. PMID 33906853.
  55. ^ Navarro-Compán V, Wei JC, Van den Bosch F, Magrey M, Wang L, Fleishaker D, et al. (June 2022). "Effect of tofacitinib on pain, fatigue, health-related quality of life and work productivity in patients with active ankylosing spondylitis: results from a phase III, randomised, double-blind, placebo-controlled trial". RMD Open. 8 (2): e002253. doi:10.1136/rmdopen-2022-002253. PMC 9163535. PMID 35654457. S2CID 249314544.
  56. ^ Vuitton L, Koch S, Peyrin-Biroulet L (November 2013). "Janus kinase inhibition with tofacitinib: changing the face of inflammatory bowel disease treatment". Current Drug Targets. 14 (12): 1385–1391. doi:10.2174/13894501113149990160. PMID 23627915.
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