Baricitinib: First Systemic Oral Drug for Alopecia Therapy
,
Abstract
Baricitinib, a Janus kinase inhibitor, was originally approved as anti-rheumatic drug in 2017. In 2020, it was approved for the treatment of COVID-19 in selected hospitalized adults. Baricitinib received priority review designation for treatment of adult patients with severe alopecia areata and got USFDA approval on June 23, 2022 based on the results of 02 phase III trial: BRAVE-AA1 and BRAVE-AA2. In this review, we aim to summarize the different pharmacokinetic and pharmacodynamics aspects including drug interactions, adverse effects/black box warnings and their clinical relevance. We reiterate that oral JAK inhibitors are expensive, may carry significant risks, and are not yet recommended for routine treatment of alopecia areata. There is ongoing research on other topical and oral JAK inhibitors (tofacitinib and ruxolitinib), giving hope that better treatments for alopecia areata will become available in future.
1.Alkhalifah A, Alsantali A, Wang E, et al. Alopecia areata update: part I. Clinical picture, histopathology, and pathogenesis. J Am Acad Dermatol. 2010; 62:177.
2. Alkhalifah A. Alopecia areata update. Dermatol Clin. 2013; 31:93–108.
3. Gandhi V, Baruah MC, Bhattacharaya SN. Nail changes in alopecia areata: Incidence and pattern. Indian J Dermatol Venereol Leprol. 2003; 69:114–5.
4. Mubki T, Rudnicka L, Olszewska M, Shapiro J. Evaluation and diagnosis of the hair loss patient: Part I. History and clinical examination. J Am Acad Dermatol. 2014; 71:415.
5. Pratt CH, King LE, Jr, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers. 2017; 3:17011.
6. Strazzulla LC, Wang EHC, Avila L. Alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol. 2018;78(1):1–12.
7. Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: A systematic review. Clin Cosmet Investig Dermatol. 2015; 8:397–403.
8. Lundin M, Chawa S, Sachdev A, et al. Gender differences in alopecia areata. J Drugs Dermatol. 2014; 13:409–13.
9. Messenger AG, McKillop J, Farrant P, et al. British Association of Dermatologists' guidelines for the management of alopecia areata 2012. Br J Dermatol. 2012; 166:916.
10. Tosti A, Bellavista S, Iorizzo M. Alopecia areata: A long term follow-up study of 191 patients. J Am Acad Dermatol. 2006; 55:438–41.
11. Jang YH, Hong NS, Moon SY, et al. Long-term prognosis of alopecia totalis and alopecia universalis: A Longitudinal study with more than 10 years of follow-up: Better than reported. Dermatology. 2017; 233:250–6.
12. Güleç AT, Tanriverdi N, Dürü C, Saray Y, Akçali C. The role of psychological factors in alopecia areata and the impact of the disease on the quality of life. Int J Dermatol. 2004; 43:352–6.
13. Brajac I, Tkalcic M, Dragojević DM, Gruber F. Roles of stress, stress perception and trait-anxiety in the onset and course of alopecia areata. J Dermatol. 2003; 30:871–8.
14. Delamere FM, Sladden MM, Dobbins HM, Leonardi-Bee J. Interventions for alopecia areata. Cochrane Database Syst Rev. 2008; CD004413.
15. Charuwichitratana S, Wattanakrai P, Tanrattanakorn S. Randomized double-blind placebo-controlled trial in the treatment of alopecia areata with 0.25% desoximetasone cream. Arch Dermatol. 2000; 136:1276–7.
16. Jahn-Bassler K, Bauer WM, Karlhofer F, Vossen MG, Stingl G. Sequential high- and low-dose systemic corticosteroid therapy for severe childhood alopecia areata. J Dtsch Dermatol Ges. 2017; 15:42–7.
17. Yoshimasu T, Kanazawa N, Yamamoto Y, Furukawa F. Multiple courses of pulse corticosteroid therapy for alopecia areata. J Dermatol. 2016; 43:1075–7.
18. Kurosawa M, Nakagawa S, Mizuashi M, et al. A comparison of the efficacy, relapse rate and side effects among three modalities of systemic corticosteroid therapy for alopecia areata. Dermatology. 2006; 212:361–5.
19. Biran R, Zlotogorski A, Ramot Y. The genetics of alopecia areata: New approaches, new findings, new treatments. J Dermatol Sci. 2015; 78:11–20.
20. Messenger A, Harries M. Baricitinib in Alopecia Areata. N Engl J Med. 2022; 386:1751-1752.
21. Jabbari A., Dai Z., Xing L. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine. 2015; 2:351–355.
22. Liu LY, Craiglow BG, Dai F. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol. 2017; 76:22–28.
23. Anzengruber F, Maul JT, Kamarachev J, et al. Transient efficacy of tofacitinib in alopecia areata universalis. Case Rep Dermatol. 2016; 8:102–6.
24. Mackay-Wiggan J, Jabbari A, Nguyen N, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;1: e89790.
25. Kennedy Crispin M, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1: e89776.
26. El Taieb MA, Ibrahim H, Nada EA, Seif Al-Din M. Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: A trichoscopic evaluation. Dermatologic therapy. 2017;30(1): Epub 2016/10/30.
27. Lattouf C, Jimenez JJ, Tosti A, et al. Treatment of alopecia areata with simvastatin/ezetimibe. J Am Acad Dermatol. 2015; 72:359–61.
28. Egesi A, Sun G, Khachemoune A, Rashid RM. Statins in skin: Research and rediscovery, from psoriasis to sclerosis. J Drugs Dermatol. 2010; 9:921–7.
29. Loi C, Starace M, Piraccini BM. Alopecia areata (AA) and treatment with simvastatin/ezetimibe: Experience of 20 patients. J Am Acad Dermatol. 2016;74: e99–e100.
30. Thompson JM, Mirza MA, Park MK, Qureshi AA, Cho E. The role of micronutrients in alopecia areata: A review. Am J Clin Dermatol. 2017; 18:663–79.
31. Brett King, Manabu Ohyama, Ohsang Kwon, et al. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022; 386:1687-1699.
32. Ito T, Tokura Y. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata. Exp Dermatol. 2014; 23:787–91.
33. Elela MA, Gawdat HI, Hegazy RA, et al. B cell activating factor and T-helper 17 cells: Possible synergistic culprits in the pathogenesis of alopecia areata. Arch Dermatol Res. 2016; 308:115–21.
34. Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014; 20:1043–9.
35. Olumiant (baricitinib) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; April 2020.
36. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939.
37. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021; 384:795-807.
38. Marconi VC, Ramanan AV, de Bono S, et al; COV-BARRIER Study Group. 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. 2021;9(12):1407-1418.
39. Olumiant (baricitinib) [prescribing information]. Indianapolis, IN: Lilly USA LLC; May 2022.
40. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529‐556.
41. Costanzo G, Firinu D, Losa F, Deidda M, Barca MP, Del Giacco S. Baricitinib exposure during pregnancy in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2020;12 :1759720X19899296.
42. Curtis JR, Lee EB, Kaplan IV. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016;75(5):831–841.
43. Smolen J, Genovese M, Winthrop K. 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.
44. Sandborn W, Panes J, D'Haens G. Safety of tofacitinib for treatment of ulcerative colitis, based on 4.4 years of data from global clinical trials. Clin Gastroenterol Hepatol. 2018 S1542-3565(18)31278-3.
45. US Food and Drug Administration (FDA). FDA Safety Alert. MedWatch. Xeljanz, Xeljanz XR (tofacitinib): FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death. Accessed June 12, 2022.
2. Alkhalifah A. Alopecia areata update. Dermatol Clin. 2013; 31:93–108.
3. Gandhi V, Baruah MC, Bhattacharaya SN. Nail changes in alopecia areata: Incidence and pattern. Indian J Dermatol Venereol Leprol. 2003; 69:114–5.
4. Mubki T, Rudnicka L, Olszewska M, Shapiro J. Evaluation and diagnosis of the hair loss patient: Part I. History and clinical examination. J Am Acad Dermatol. 2014; 71:415.
5. Pratt CH, King LE, Jr, Messenger AG, Christiano AM, Sundberg JP. Alopecia areata. Nat Rev Dis Primers. 2017; 3:17011.
6. Strazzulla LC, Wang EHC, Avila L. Alopecia areata: disease characteristics, clinical evaluation, and new perspectives on pathogenesis. J Am Acad Dermatol. 2018;78(1):1–12.
7. Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: A systematic review. Clin Cosmet Investig Dermatol. 2015; 8:397–403.
8. Lundin M, Chawa S, Sachdev A, et al. Gender differences in alopecia areata. J Drugs Dermatol. 2014; 13:409–13.
9. Messenger AG, McKillop J, Farrant P, et al. British Association of Dermatologists' guidelines for the management of alopecia areata 2012. Br J Dermatol. 2012; 166:916.
10. Tosti A, Bellavista S, Iorizzo M. Alopecia areata: A long term follow-up study of 191 patients. J Am Acad Dermatol. 2006; 55:438–41.
11. Jang YH, Hong NS, Moon SY, et al. Long-term prognosis of alopecia totalis and alopecia universalis: A Longitudinal study with more than 10 years of follow-up: Better than reported. Dermatology. 2017; 233:250–6.
12. Güleç AT, Tanriverdi N, Dürü C, Saray Y, Akçali C. The role of psychological factors in alopecia areata and the impact of the disease on the quality of life. Int J Dermatol. 2004; 43:352–6.
13. Brajac I, Tkalcic M, Dragojević DM, Gruber F. Roles of stress, stress perception and trait-anxiety in the onset and course of alopecia areata. J Dermatol. 2003; 30:871–8.
14. Delamere FM, Sladden MM, Dobbins HM, Leonardi-Bee J. Interventions for alopecia areata. Cochrane Database Syst Rev. 2008; CD004413.
15. Charuwichitratana S, Wattanakrai P, Tanrattanakorn S. Randomized double-blind placebo-controlled trial in the treatment of alopecia areata with 0.25% desoximetasone cream. Arch Dermatol. 2000; 136:1276–7.
16. Jahn-Bassler K, Bauer WM, Karlhofer F, Vossen MG, Stingl G. Sequential high- and low-dose systemic corticosteroid therapy for severe childhood alopecia areata. J Dtsch Dermatol Ges. 2017; 15:42–7.
17. Yoshimasu T, Kanazawa N, Yamamoto Y, Furukawa F. Multiple courses of pulse corticosteroid therapy for alopecia areata. J Dermatol. 2016; 43:1075–7.
18. Kurosawa M, Nakagawa S, Mizuashi M, et al. A comparison of the efficacy, relapse rate and side effects among three modalities of systemic corticosteroid therapy for alopecia areata. Dermatology. 2006; 212:361–5.
19. Biran R, Zlotogorski A, Ramot Y. The genetics of alopecia areata: New approaches, new findings, new treatments. J Dermatol Sci. 2015; 78:11–20.
20. Messenger A, Harries M. Baricitinib in Alopecia Areata. N Engl J Med. 2022; 386:1751-1752.
21. Jabbari A., Dai Z., Xing L. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine. 2015; 2:351–355.
22. Liu LY, Craiglow BG, Dai F. Tofacitinib for the treatment of severe alopecia areata and variants: a study of 90 patients. J Am Acad Dermatol. 2017; 76:22–28.
23. Anzengruber F, Maul JT, Kamarachev J, et al. Transient efficacy of tofacitinib in alopecia areata universalis. Case Rep Dermatol. 2016; 8:102–6.
24. Mackay-Wiggan J, Jabbari A, Nguyen N, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;1: e89790.
25. Kennedy Crispin M, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1: e89776.
26. El Taieb MA, Ibrahim H, Nada EA, Seif Al-Din M. Platelets rich plasma versus minoxidil 5% in treatment of alopecia areata: A trichoscopic evaluation. Dermatologic therapy. 2017;30(1): Epub 2016/10/30.
27. Lattouf C, Jimenez JJ, Tosti A, et al. Treatment of alopecia areata with simvastatin/ezetimibe. J Am Acad Dermatol. 2015; 72:359–61.
28. Egesi A, Sun G, Khachemoune A, Rashid RM. Statins in skin: Research and rediscovery, from psoriasis to sclerosis. J Drugs Dermatol. 2010; 9:921–7.
29. Loi C, Starace M, Piraccini BM. Alopecia areata (AA) and treatment with simvastatin/ezetimibe: Experience of 20 patients. J Am Acad Dermatol. 2016;74: e99–e100.
30. Thompson JM, Mirza MA, Park MK, Qureshi AA, Cho E. The role of micronutrients in alopecia areata: A review. Am J Clin Dermatol. 2017; 18:663–79.
31. Brett King, Manabu Ohyama, Ohsang Kwon, et al. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022; 386:1687-1699.
32. Ito T, Tokura Y. The role of cytokines and chemokines in the T-cell-mediated autoimmune process in alopecia areata. Exp Dermatol. 2014; 23:787–91.
33. Elela MA, Gawdat HI, Hegazy RA, et al. B cell activating factor and T-helper 17 cells: Possible synergistic culprits in the pathogenesis of alopecia areata. Arch Dermatol Res. 2016; 308:115–21.
34. Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition. Nat Med. 2014; 20:1043–9.
35. Olumiant (baricitinib) [product monograph]. Toronto, Ontario, Canada: Eli Lilly Canada Inc; April 2020.
36. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2021;73(7):924-939.
37. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med. 2021; 384:795-807.
38. Marconi VC, Ramanan AV, de Bono S, et al; COV-BARRIER Study Group. 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. 2021;9(12):1407-1418.
39. Olumiant (baricitinib) [prescribing information]. Indianapolis, IN: Lilly USA LLC; May 2022.
40. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529‐556.
41. Costanzo G, Firinu D, Losa F, Deidda M, Barca MP, Del Giacco S. Baricitinib exposure during pregnancy in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2020;12 :1759720X19899296.
42. Curtis JR, Lee EB, Kaplan IV. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016;75(5):831–841.
43. Smolen J, Genovese M, Winthrop K. 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.
44. Sandborn W, Panes J, D'Haens G. Safety of tofacitinib for treatment of ulcerative colitis, based on 4.4 years of data from global clinical trials. Clin Gastroenterol Hepatol. 2018 S1542-3565(18)31278-3.
45. US Food and Drug Administration (FDA). FDA Safety Alert. MedWatch. Xeljanz, Xeljanz XR (tofacitinib): FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death. Accessed June 12, 2022.
| Files | ||
| Issue | Vol 10, No 3 (Summer 2022) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/jpc.v10i3.10797 | |
| Keywords | ||
| Alopecia Baricitinib Hair Follicle Janus Kinase Inhibitors | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Mishra P, Sinha S, Vihan S, Dahiya N, Vasudevan B. Baricitinib: First Systemic Oral Drug for Alopecia Therapy. J Pharm Care. 2022;10(3):167-174.
