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 Table of Contents  
REVIEW ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 6-13

Janus Kinase Inhibitors in Dermatology


Department of Dermatology, IQ City Medical College, Durgapur, West Bengal, India

Date of Web Publication22-Jul-2019

Correspondence Address:
Dr. Aditya Kumar Bubna
IQ City Medical College, Sovapur, Bijra Road, Jemua, Durgapur - 713 206, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdd.ijdd_38_18

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  Abstract 


Janus kinase (JAK) inhibitors are a new addition in the armamentarium of drugs in the treatment of autoimmune dermatoses. They have proven to be valuable in treating a variety of inflammatory dermatoses with lesser side effects compared to their biological counterparts. This review throws light on JAK inhibitors and their role in dermatologic diseases.

Keywords: Alopecia areata, atopic dermatitis, psoriasis, tofacitinib, vitiligo


How to cite this article:
Bubna AK. Janus Kinase Inhibitors in Dermatology. Indian J Drugs Dermatol 2019;5:6-13

How to cite this URL:
Bubna AK. Janus Kinase Inhibitors in Dermatology. Indian J Drugs Dermatol [serial online] 2019 [cited 2019 Nov 13];5:6-13. Available from: http://www.ijdd.in/text.asp?2019/5/1/6/263100




  Introduction Top


With the emergence of new molecular targeted therapies, the picture of therapeutic dermatology is gradually evolving. One such molecular target is the Janus kinase-signal transducer and activation of transcription (JAK-STAT) pathway.

A number of inflammatory dermatoses rely on the JAK-STAT pathway for their pathogenesis. Therefore, utilizing JAK inhibitors may prove to be valuable in targeting the pathogenesis of these disorders. A number of JAK inhibitors have been utilized. Broadly, they have been classified into first-generation JAK inhibitors that include tofacitinib, ruxolitinib, baricitinib, and oclacitinib and second-generation JAK inhibitors that comprise decernotinib, peficitinib, filgotinib, fedratinib, momelotinib, and lestaurtinib. Currently, only the first-generation JAK inhibitors are being utilized in the management of dermatological disorders and are lucidly outlined in [Table 1]. The second-generation JAK inhibitors at present are in their developmental stage.
Table 1: Details of first-generation Janus kinase inhibitors

Click here to view



  Mechanism of Action Top


In atopic dermatitis

It has been proved that JAK-STAT signaling pathway enhances release of interleukin (IL)-4, IL-5 and IL-13, which play an important role in stimulating TH2 differentiation. In experimental models, tofacitinib and oclacitinib have demonstrated an antagonizing effect on the release of the above cytokines, thereby blocking their inflammatory activity.[6],[7],[8]

In alopecia areata

In alopecia areata (AA), JAK-STAT-dependent cytokines along with interferon (IFN) γ and IL-15 activate autoreactive T-cells.[9] JAK inhibition can prevent the release of these inflammatory cytokines, thereby bringing a halt to the pathogenetic process.

In psoriasis

IL-12 and IL-23 are JAK-STAT-dependent cytokines which majorly serve as inflammatory mediators in psoriasis. Further, IL-23 stimulates TH17 cells to produce IL-17, another important pathogenic molecule in psoriasis. Although IL-17 does not directly rely on JAK-STAT signaling pathway, blockade of IL-23 by JAK inhibitors reduces IL-17, and therefore, these drugs have value in psoriasis.[6],[10],[11]

In vitiligo

It has been demonstrated that depigmentation in vitiligo is mediated by IFN γ-induced expression of C-X-C motif chemokine 10 (CXCL 10) in keratinocytes.[12] As IFN γ signal transduction occurs through JAK 1 and 2, blockade of JAK with tofacitinib inhibits IFN γ signaling, thereby downregulating CXCL 10 expression, leading to return in pigmentation.[13]


  Pharmacokinetics Top


As tofacitinib is the prototype drug for JAK inhibitors, its pharmacokinetics are discussed in this section. Tofacitinib is rapidly absorbed after oral administration with plasma levels peaking after 1 h of oral intake. Tofacitinib has been demonstrated to have a mean terminal plasma half-life of 3.2 h. Metabolism of tofacitinib occurs in the liver by oxidation, N-demethylation, and glucuronidation. Elimination of tofacitinib occurs via both the hepatic (70%) and renal (30%) routes.[14]


  Indications Top


Food and Drug Administration approved

  • Rheumatoid arthritis (tofacitinib, baricitinib)
  • Myelofibrosis and polycythemia rubra vera (ruxolitinib).


Off label

  • All cutaneous indications as mentioned below.



  Contraindications Top


Absolute

  • Hypersensitivity to the drug.


Relative

  • Liver impairment
  • Stage IV kidney disease
  • Active infections.


Pregnancy prescribing status

  • Category “C.”



  Clinical Uses Top


Atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory condition of the skin associated with significant pruritus.[15] It affects around 10%–30% patients in the pediatric age group and around 1%–3% of the adult population.[16] Currently, the mainstay of pharmacologic therapy in AD comprises topical corticosteroids, topical calcineurin inhibitors, and phototherapy, with systemic immunosuppressive drugs such as cyclosporine, methotrexate, mycophenolate mofetil, and azathioprine being added to the therapeutic armamentarium in recalcitrant cases.[17],[18] These therapies, however, are often insufficient for moderate-to-severe disease.[19],[20] Recent advances in the pathogenesis of AD have demonstrated the utility of tofacitinib, both topically and systemically as a new targeted therapeutic modality for AD.

Levy et al.[21] have reported the clinical efficacy of systemic tofacitinib in six patients aged between 18 and 55 years, with moderate-to-severe AD who were resistant to previous therapies with other immunosuppressive drugs as mentioned above. In these patients, tofacitinib was administered at a dose of 5 mg PO twice daily or once daily, along with concomitant use of topical corticosteroids which resulted in 66.6% reduction in the severity scoring of AD index and 69.9% reduction in pruritus and sleep loss. This was observed after 8-29 weeks of treatment. During this limited series, no adverse events were observed.

A recently published study utilizing 2% tofacitinib ointment in 69 adult patients with mild-to-moderate AD resulted in 81.7% diminution of the eczema area and severity index score at 4 weeks relative to a decrease of 29.9% in the placebo group.[22]

In both the above observations, a stable and significant improvement of the disease was witnessed. Further, a favorable adverse effect profile was also documented in both reports. However, larger randomized controlled trials would be required to further establish the safety profile and efficacy of systemic tofacitinib for moderate-to-severe AD.

Alopecia areata

AA is an autoimmune disorder demonstrating patches of nonscarring alopecia that can involve any area of the body.[23] Currently, no particular treatment has been approved by the US Food and Drug Administration (FDA) for the management of AA. Many off-label treatments are available, but the efficacy of most of them is limited, thereby making room for newer alternatives in treating AA. Increasing evidence elucidates avaluable and effective contribution by JAK inhibitors in the treatment of AA and is summarized in [Table 2].
Table 2: Various studies depicting the positive effects of Janus kinase inhibitors in alopecia areata

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Psoriasis

Psoriasis is a common, chronic, inflammatory disease of multifactorial origin affecting 1%–3% of the world's population. Chronic plaque psoriasis is the most common manifestation of the disease that is clinically characterized by well-defined erythematous and scaly plaques.

Despite there being a number of treatments available for psoriasis, additional therapeutic options with a distinctive targeted effect would certainly be of value in managing the disease.[35] It has also been observed that the overall efficacy of tumor necrosis factor (TNF)-α blockers diminishes over time owing to their potential immunogenicity.[36] Further, the body mass index also affects the long-term survival rate of TNFα antagonists in patients with psoriasis.[37]

Recently, attention has shifted to newer compounds targeting signaling pathways such as JAK inhibitors. These small molecular weight inhibitors are synthetic compounds that are relatively inexpensive and can be administered both topically and systemically.[38] They have been utilized in psoriasis with promising results. The FDA has yet to approve tofacitinib for this indication. Various studies depicting the utility of JAK inhibitors for psoriasis are summarized in [Table 3].
Table 3: Studies depicting the utility of Janus-kinase inhibitors in psoriasis

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Vitiligo

Vitiligo is an autoimmune disease associated with skin and mucosal depigmentation. Though not a life-threatening disease, vitiligo is associated with profound psychological implications on the patient's quality of life. Available treatment options for vitiligo are limited and often inadequate. Recent studies on the pathogenesis of vitiligo have suggested the possibility of JAK inhibitors as an effective therapy for the same.[12]

Harris et al.[47] have reported significant repigmentation of vitiligo in a patient with both AA and vitiligo with administration of ruxolitinib 20 mg PO twice daily for 24 weeks. However, depigmentation recurred after discontinuation of the drug.

Another case report by Craiglow and King[48] demonstrated the promising effect of tofacitinib in vitiligo vulgaris in a middle-aged woman who had been unresponsive to topical triamcinolone (0.1%), topical tacrolimus (0.1%), and narrow-band ultraviolet B (UVB) phototherapy. Tofacitinib was first initiated at a dose of 5 mg PO on alternate days for 3 weeks, followed by 5 mg/day for 5 months. After the stated duration, patient experienced nearly complete repigmentation over the forehead and hands and only 5% of the total lesions overall remained depigmented. Further, the safety profile of the drug was also favorable.

Also, rapid repigmentation of vitiligo utilizing tofacitinib along with low-dose narrow band UVB has been documented by Kim et al.,[49] thereby demonstrating synergism while combining these treatment modalities.

Dermatomyositis

Studies have suggested the role of tofacitinib in refractory cutaneous dermatomyositis (DM). Tofacitinib acts by suppressing the abnormally upregulated IFN signaling in DM.[50],[51] In one series, three patients with refractory DM observed clinical response after treatment with oral tofacitinib at a dose of 5–10 mg/day. The mean treatment period was 9.6 months. By the end of 4 weeks of treatment, clinical improvement was noticeable with respect to pruritus and muscle strength.[52] Improvement from moderate-to-severe to mild disease was observed in two patients. In both these patients, tofacitinib was employed as monotherapy after failure of previous conventional therapies. The third patient demonstrated a lesser response though the response was clinically significant.

In a case report by Hornung et al.,[53] ruxolitinib was used to treat recalcitrant DM in a 72-year-old patient who also had polycythemia rubra vera and myelofibrosis. Here, ruxolitinib was administered at a dose of 5 mg PO Q12H for 2 months, which was then increased to 15 mg PO Q12H for 12 months, followed by 10 mg twice daily. Therapy with ruxolitinib was associated with improvement of both cutaneous and musculoskeletal symptoms of DM. Further, no adverse effects were reported in this patient.

Lichen planopilaris

Lichen planopilaris (LPP) is an inflammatory cicatricial alopecia of unclear etiology, whose treatment still remains a challenge. Many different treatment modalities have been advocated for LPP with varying success. A recent study has demonstrated upregulation of JAK1 and JAK3 in dermal inflammatory cells of LPP, thereby postulating a role of JAK inhibitors in reducing IFN-mediated inflammation associated with LPP and in this way preventing further destruction of hair follicles.[54]

In a case series of 10 patients of LPP (aged between 33 and 68 years) treated with oral tofacitinib (10–15 mg/day) for 2–9 months, improvement in erythema, scaling, and hair density was witnessed in eight out of 10 patients. Further, symptoms such as pruritus, pain, and burning demonstrated significant reduction. Of these 10 patients, five received tofacitinib monotherapy with the remaining five also receiving intralesional triamcinolone (2 patients), hydroxychloroquine (1 patient), hydroxychloroquine and triamcinolone (1 patient), and intralesional triamcinolone with topical tacrolimus (1 patient). In all patients, treatment with tofacitinib was well tolerated with no adverse effects being reported.[55]

Lupus erythematosus

In a case report by Wenzel et al.,[56] ruxolitinib dosed at 20 mg PO Q12H for 4 months in a 69-year-old patient with chilblain lupus was associated with complete remission of the condition.


  Special Consideration Top


Use of Janus kinase inhibitors in the pediatric population

In most of the studies pertaining to JAK inhibitors, it has been seen that either adults or adolescents constituted the study population. However, there are a few reports depicting the utility of these drugs in children and have been elaborated in [Table 4]. Though not associated with major adverse responses, the use of systemic JAK inhibitors should be exercised with caution in children. More studies in this age group would further help in delineating the safety profile of JAK inhibitors in the pediatric population.
Table 4: Studies utilizing Janus kinase inhibitors for treating dermatologic conditions in the pediatric population

Click here to view



  Adverse Effects Top


  • Risk of urinary tract infection, nasopharyngitis, and upper respiratory tract infections
  • Varicella-zoster virus reactivation
  • Impaired response to vaccination
  • Thrombocytopenia, anemia
  • Diarrhea, fatigue, dizziness, and headache
  • Increased risk of malignancies.



  Monitoring Guidelines Top


Baseline

  • Complete blood count
  • Renal function tests
  • Liver function tests
  • Fasting lipid profile
  • HBsAg
  • Anti-HCV
  • Testing for tuberculosis (to be done at baseline and then once every year)
  • HIV status.


After 1 month

  • Complete blood count
  • Renal function tests
  • Liver function tests
  • Fasting lipid profile.


Once every 3 months

  • Complete blood count
  • Renal function tests
  • Liver function tests
  • Fasting lipid profile.



  Conclusion Top


In addition to the entities discussed, JAK inhibitors have also shown to be of value in chronic actinic dermatitis, erythema multiforme, cutaneous graft versus host disease, allergic contact dermatitis, melanoma, and cutaneous T-cell lymphoma.[60],[61],[62],[63],[64],[65]

Based on the currently available data, tofacitinib has been found to be comparable with etanercept as a second-line agent for psoriasis. Further, owing to its oral route of administration and better economic profile over biologic drugs, tofacitinib again scores above them.

Moreover, when compared with other immunosuppressive drugs such as methotrexate, cyclosporine, azathioprine, and mycophenolate mofetil, JAK inhibitors have again elucidated superior results. Also, with topical preparations of JAK inhibitors being available, it could prove beneficial in those patients where systemic therapy with the drug is contraindicated or in milder disease phenotypes where topical therapy would suffice in bringing about disease remission, thereby representing a safer alternative for a number of chronic dermatologic diseases. However, more head-to-head comparative studies with respect to these drugs would further help in delineating things better. Overall, JAK inhibitors are a relatively safe group of drugs.

Today, JAK inhibitors are the subject of intensive research as they represent possible therapeutic targets in a number of cutaneous diseases.

Availability

  • Tofacitinib is marketed as a 5 mg tablet under the brand name Xeljanz
  • Ruxolitinib is marketed as 5, 15, and 20 mg tablets under the brand name Jakavi
  • Baricitinib is marketed as 2 and 4 mg tablets under the brand name Olumiant
  • Tofacitinib is available as a 2% ointment
  • Ruxolitinib is available as a 0.6% ointment.


In India, currently, only the oral preparations of the above-mentioned JAK inhibitors are available.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Changelian PS, Flanagan ME, Ball DJ, Kent CR, Magnuson KS, Martin WH, et al. Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 2003;302:875-8.  Back to cited text no. 1
    
2.
Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Eng J Med 2016;374:1243-52.  Back to cited text no. 2
    
3.
Papp KA, Menter MA, Raman M, Disch D, Schlichting DE, Gaich C, et al. Arandomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol 2016;174:1266-76.  Back to cited text no. 3
    
4.
Cosgrove SB, Wren JA, Cleaver DM, Walsh KF, Follis SI, King VI, et al. Ablinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis. Vet Dermatol 2013;24:587-97, e141-2.  Back to cited text no. 4
    
5.
Gonzales AJ, Bowman JW, Fici GJ, Zhang M, Mann DW, Mitton-Fry M. Oclacitinib (Apoquel®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. J Vet Pharmacol Ther 2014;37:317-24.  Back to cited text no. 5
    
6.
Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol 2011;186:4234-43.  Back to cited text no. 6
    
7.
Leung DY, Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches. J Allergy Clin Immunol 2014;134:769-79.  Back to cited text no. 7
    
8.
Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT 2013;2:e24137.  Back to cited text no. 8
    
9.
Gilhar A, Schrum AG, Etzioni A, Waldmann H, Paus R. Alopecia areata: animal models illuminate autoimmue pathogenesis and novel immunotherapeutic strategies. Autoimmune Rev 2016;15:726-35  Back to cited text no. 9
    
10.
Teng MW, Bowman EP, McElwee JJ, Smyth MJ, Casanova JL, Cooper AM, et al. IL-12 and IL-23 cytokines: From discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med 2015;21:719-29.  Back to cited text no. 10
    
11.
Di Lernia V, Bardazzi F. Profile of tofacitinib citrate and its potential in the treatment of mild to moderate chronic plaque psoriasis. Drug Des Devel Ther 2016;10:533-9.  Back to cited text no. 11
    
12.
Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su MW, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med 2014;6:223ra23.  Back to cited text no. 12
    
13.
O'Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med 2013;368:161-70.  Back to cited text no. 13
    
14.
Dowty ME, Lin J, Ryder TF, Wang W, Walker GS, Vaz A, et al. The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a Janus kinase inhibitor, in humans. Drug Metab Dispos 2014;42:759-73.  Back to cited text no. 14
    
15.
Kini SP, DeLong LK, Veledar E, McKenzie-Brown AM, Schaufele M, Chen SC, et al. The impact of pruritus on quality of life: The skin equivalent of pain. Arch Dermatol 2011;147:1153-6.  Back to cited text no. 15
    
16.
Schmitt J, Bauer A, Meurer M. Atopic exzema in adulthood. Hautarzt 2008;59:841-50.  Back to cited text no. 16
    
17.
Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol 2014;71:116-32.  Back to cited text no. 17
    
18.
Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, et al. Guidelines of care for the management of atopic dermatitis: Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol 2014;71:327-49.  Back to cited text no. 18
    
19.
Garritsen FM, Roekevisch E, van der Schaft J, Deinum J, Spuls PI, de Bruin-Weller MS, et al. Ten years experience with oral immunosuppressive treatment in adult patients with atopic dermatitis in two academic centres. J Eur Acad Dermatol Venereol 2015;29:1905-12.  Back to cited text no. 19
    
20.
Schram ME, Roekevisch E, Leeflang MM, Bos JD, Schmitt J, Spuls PI, et al. Arandomized trial of methotrexate versus azathioprine for severe atopic eczema. J Allergy Clin Immunol 2011;128:353-9.  Back to cited text no. 20
    
21.
Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol 2015;73:395-9.  Back to cited text no. 21
    
22.
Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: A phase IIa randomized trial. Br J Dermatol 2016;175:902-11.  Back to cited text no. 22
    
23.
Islam N, Leung PS, Huntley AC, Gershwin ME. The autoimmune basis of alopecia areata: A comprehensive review. Autoimmun Rev 2015;14:81-9.  Back to cited text no. 23
    
24.
Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, et al. Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight 2016;1:e89776.  Back to cited text no. 24
    
25.
Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, et al. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight 2016;1:e89790.  Back to cited text no. 25
    
26.
Dhayalan A, King BA. Tofacitinib citrate for the treatment of nail dystrophy associated with alopecia universalis. JAMA Dermatol 2016;152:492-3.  Back to cited text no. 26
    
27.
Craiglow BG, Tavares D, King BA. Topical ruxolitinib for the treatment of alopecia universalis. JAMA Dermatol 2016;152:490-1.  Back to cited text no. 27
    
28.
Craiglow BG, King BA. Killing two birds with one stone: Oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis. J Invest Dermatol 2014;134:2988-90  Back to cited text no. 28
    
29.
Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol 2017;76:22-8.  Back to cited text no. 29
    
30.
Anzengruber F, Maul JT, Kamarachev J, Trüeb RM, French LE, Navarini AA, et al. Transient efficacy of tofacitinib in alopecia areata universalis. Case Rep Dermatol 2016;8:102-6.  Back to cited text no. 30
    
31.
Jabbari A, Nguyen N, Cerise JE, Ulerio G, de Jong A, Clynes R, et al. Treatment of an alopecia areata patient with tofacitinib results in regrowth of hair and changes in serum and skin biomarkers. Exp Dermatol 2016;25:642-3.  Back to cited text no. 31
    
32.
Mrowietz U, Gerdes S, Gläser R, Schröder O. Successful treatment of refractory alopecia areata universalis and psoriatic arthritis, but not of plaque psoriasis with tofacitinib in a young woman. Acta Derm Venereol 2017;97:283-4.  Back to cited text no. 32
    
33.
Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol 2017;76:29-32.  Back to cited text no. 33
    
34.
Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y, et al. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine 2015;2:351-5.  Back to cited text no. 34
    
35.
Dubois Declercq S, Pouliot R. Promising new treatments for psoriasis. ScientificWorldJournal 2013;2013:980419.  Back to cited text no. 35
    
36.
De Simone C, Amerio P, Amoruso G, Bardazzi F, Campanati A, Conti A, et al. Immunogenicity of anti-TNFα therapy in psoriasis: A clinical issue? Expert Opin Biol Ther 2013;13:1673-82.  Back to cited text no. 36
    
37.
Di Lernia V, Tasin L, Pellicano R, Zumiani G, Albertini G. Impact of body mass index on retention rates of anti-TNF-alfa drugs in daily practice for psoriasis. J Dermatolog Treat 2012;23:404-9.  Back to cited text no. 37
    
38.
Mansouri Y, Goldenberg G. New systemic therapies for psoriasis. Cutis 2015;95:155-60.  Back to cited text no. 38
    
39.
Bachelez H, van de Kerkhof PC, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: A phase 3 randomised non-inferiority trial. Lancet 2015;386:552-61.  Back to cited text no. 39
    
40.
Punwani N, Burn T, Scherle P, Flores R, Shi J, Collier P, et al. Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor. Br J Dermatol 2015;173:989-97.  Back to cited text no. 40
    
41.
Ports WC, Khan S, Lan S, Lamba M, Bolduc C, Bissonnette R, et al. Arandomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol 2013;169:137-45.  Back to cited text no. 41
    
42.
Menter A, Papp KA, Tan H, Tyring S, Wolk R, Buonanno M, et al. Efficacy of tofacitinib, an oral Janus kinase inhibitor, on clinical signs of moderate-to-severe plaque psoriasis in different body regions. J Drugs Dermatol 2014;13:252-6.  Back to cited text no. 42
    
43.
Mamolo C, Harness J, Tan H, Menter A. Tofacitinib (CP-690,550), an oral Janus kinase inhibitor, improves patient-reported outcomes in a phase 2b, randomized, double-blind, placebo-controlled study in patients with moderate-to-severe psoriasis. J Eur Acad Dermatol Venereol 2014;28:192-203.  Back to cited text no. 43
    
44.
Krueger J, Clark JD, Suárez-Fariñas M, Fuentes-Duculan J, Cueto I, Wang CQ, et al. Tofacitinib attenuates pathologic immune pathways in patients with psoriasis: A randomized phase 2 study. J Allergy Clin Immunol 2016;137:1079-90.  Back to cited text no. 44
    
45.
Menter MA, Papp KA, Cather J, Leonardi C, Pariser DM, Krueger JG, et al. Efficacy of tofacitinib for the treatment of moderate-to-severe chronic plaque psoriasis in patient subgroups from two randomised phase 3 trials. J Drugs Dermatol 2016;15:568-80.  Back to cited text no. 45
    
46.
Valenzuela F, Paul C, Mallbris L, Tan H, Papacharalambous J, Valdez H, et al. Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: Patient-reported outcomes from a phase 3 study. J Eur Acad Dermatol Venereol 2016;30:1753-9.  Back to cited text no. 46
    
47.
Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G, Clynes R, et al. Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol 2016;74:370-1.  Back to cited text no. 47
    
48.
Craiglow BG, King BA. Tofacitinib citrate for the treatment of vitiligo: A pathogenesis-directed therapy. JAMA Dermatol 2015;151:1110-2.  Back to cited text no. 48
    
49.
Kim SR, Heaton H, Liu LY, King BA. Rapid repigmentation of vitiligo using tofacitinib plus low-dose, narrowband UV-B phototherapy. JAMA Dermatol 2018;154:370-1.  Back to cited text no. 49
    
50.
Rosengren S, Corr M, Firestein GS, Boyle DL. The JAK inhibitor CP-690,550 (tofacitinib) inhibits TNF-induced chemokine expression in fibroblast-like synoviocytes: Autocrine role of type I interferon. Ann Rheum Dis 2012;71:440-7.  Back to cited text no. 50
    
51.
Kao L, Chung L, Fiorentino DF. Pathogenesis of dermatomyositis: Role of cytokines and interferon. Curr Rheumatol Rep 2011;13:225-32.  Back to cited text no. 51
    
52.
Kurtzman DJ, Wright NA, Lin J, Femia AN, Merola JF, Patel M, et al. Tofacitinib citrate for refractory cutaneous dermatomyositis: An alternative treatment. JAMA Dermatol 2016;152:944-5.  Back to cited text no. 52
    
53.
Hornung T, Janzen V, Heidgen FJ, Wolf D, Bieber T, Wenzel J, et al. Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med 2014;371:2537-8.  Back to cited text no. 53
    
54.
Alves de Medeiros AK, Speeckaert R, Desmet E, Van Gele M, De Schepper S, Lambert J, et al. JAK3 as an emerging target for topical treatment of inflammatory skin diseases. PLoS One 2016;11:e0164080.  Back to cited text no. 54
    
55.
Yang CC, Khanna T, Sallee B, Christiano AM, Bordone LA. Tofacitinib for the treatment of lichen planopilaris: A case series. Dermatol Ther 2018;31:e12656.  Back to cited text no. 55
    
56.
Wenzel J, van Holt N, Maier J, Vonnahme M, Bieber T, Wolf D, et al. JAK1/2 inhibitor ruxolitinib controls a case of chilblain lupus erythematosus. J Invest Dermatol 2016;136:1281-3.  Back to cited text no. 56
    
57.
Frémond ML, Rodero MP, Jeremiah N, Belot A, Jeziorski E, Duffy D, et al. Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. J Allergy Clin Immunol 2016;138:1752-5.  Back to cited text no. 57
    
58.
Bayart CB, DeNiro KL, Brichta L, Craiglow BG, Sidbury R. Topical Janus kinase inhibitors for the treatment of pediatric alopecia areata. J Am Acad Dermatol 2017;77:167-70.  Back to cited text no. 58
    
59.
Brown L, Skopit S. An excellent response to tofacitinib in a pediatric alopecia patient: A Case report and review. J Drugs Dermatol 2018;17:914-7.  Back to cited text no. 59
    
60.
Vesely MD, Imaeda S, King BA. Tofacitinib citrate for the treatment of refractory, severe chronic actinic dermatitis. JAAD Case Rep 2017;3:4-6.  Back to cited text no. 60
    
61.
Damsky W, King BA. Idiopathic erythema multiforme: Evidence of underlying Janus Kinase-signal transducer and activator of transcription activation and successful treatment with tofacitinib. JAAD Case Rep 2016;2:502-4.  Back to cited text no. 61
    
62.
Zeiser R, Burchert A, Lengerke C, Verbeek M, Maas-Bauer K, Metzelder SK, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: A multicenter survey. Leukemia 2015;29:2062-8.  Back to cited text no. 62
    
63.
Fukuyama T, Ehling S, Cook E, Bäumer W. Topically administered Janus-Kinase inhibitors tofacitinib and oclacitinib display impressive antipruritic and anti-inflammatory responses in a model of allergic dermatitis. J Pharmacol Exp Ther 2015;354:394-405.  Back to cited text no. 63
    
64.
Wu KJ, Huang JM, Zhong HJ, Dong ZZ, Vellaisamy K, Lu JJ, et al. Anatural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells. PLoS One 2017;12:e0177123.  Back to cited text no. 64
    
65.
Litvinov IV, Pehr K, Sasseville D. Connecting the dots in cutaneous T cell lymphoma (CTCL): STAT5 regulates malignant T cell proliferation via miR-155. Cell Cycle 2013;12:2172-3.  Back to cited text no. 65
    



 
 
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Abstract
Introduction
Mechanism of Action
Pharmacokinetics
Indications
Contraindications
Clinical Uses
Special Consider...
Adverse Effects
Monitoring Guide...
Conclusion
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