1Division of Dermatology, University of Calgary, Calgary, AB, Canada
2Queen’s University School of Medicine, Queen’s University, Kingston, ON, Canada
Conflict of interest:
The authors have no conflicts to disclose.
The class of medications known as Janus kinase inhibitors block cytokine-mediated signaling via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, which plays an important role in immunoregulation and normal cell growth. This class includes the drugs tofacitinib, approved for the treatment of rheumatoid arthritis, and ruxolitinib, approved for the treatment of myelofibrosis and polycythemia rubra vera. The most common adverse events (AEs) reported in patients taking tofacitinib are infections, whereas the most common AEs in patients taking ruxolitinib are anemia and thrombocytopenia. Both first and second generation Janus kinase inhibitors have become promising treatment modalities for dermatologic conditions such as psoriasis, atopic dermatitis, alopecia areata, vitiligo, dermatomyositis, and graft-versus-host disease. Future promising areas of investigation include treatment of cutaneous lupus, cutaneous T-cell lymphoma, melanoma, allergic contact dermatitis, and lichen planus.
Janus kinase inhibitors, JAK inhibitors, JAK-STAT pathway, tofacitinib, ruxolitinib, alopecia areata, atopic dermatitis, dermatomyositis, graft-versus-host disease, psoriasis, vitiligo
The JAK-STAT Pathway
The development and function of various human cells are controlled by a group of secreted factors known as cytokines. One large subgroup of cytokines, which play a critical role in the signaling systems that underlie normal cell growth and immunoregulation, bind to type 1 or 2 cytokine receptors. The cytokines in this group use the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway as a mode of signal transduction.1
When a cytokine binds to a type 1 or 2 receptor on the cell membrane, the receptor dimerizes, allowing the associated cytoplasmic JAK protein to autophosphorylate and phosphorylate the receptor chains.2,3 This process induces recruitment of signaling intermediaries including STAT proteins that transduce the signal from the cytokine receptor to the nucleus, leading to DNA transcription and regulation of gene expression.1
There are four different members of the JAK family – JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Mutations and polymorphisms within this JAK-STAT pathway have been implicated in both autoimmune and malignant processes. For example, mutations of JAK3 and TYK2 are known causes of immunodeficiency, whereas polymorphisms of JAK2 and STAT3 contribute to a range of autoimmune diseases, including inflammatory bowel disease, psoriasis, ankylosing spondylitis and Behcet’s disease.1 Acquired mutations in JAK2 have been noted in more than half of patients with myeloproliferative neoplasms, including polycythemia rubra vera, essential thrombocythemia, and primary myelofibrosis.4
JAK inhibitors, or jakinibs, inhibit the kinase component of JAKs, thereby preventing them from phosphorylating and stopping the transduction of intracellular signaling. First generation jakinibs, which include the drugs tofacitinib and ruxolitinib, inhibit multiple JAKs. Tofacitinib, which is approved as monotherapy or in combination with methotrexate for the treatment of rheumatoid arthritis, inhibits JAK1 and JAK3, and to a lesser extent the other JAK isoforms. Ruxolitinib, which is approved for use in myelofibrosis and polycythemia rubra vera, inhibits JAK1 and JAK2.5 Second generation jakinibs are still under investigation and more selectively target only one JAK isoform, thereby inhibiting a narrower range of cytokines.6 (Table 1)
|Tofacitinib||1st generation||JAK3, JAK1, JAK2 (to a lesser extent)||FDA approved|
FDA approval recommended
|Ruxolitinib||1st generation||JAK1, JAK2||Phase III|
Atopic dermatitis (topical)
|Baricitinib||1st generation||JAK1, JAK2||Phase II|
|Oclacitinib||1st generation||JAK1||FDA approved||Canine allergic dermatitis|
|Upadacitinib||2nd generation||JAK1||Phase II||Atopic dermatitis|
|Itacitinib||2nd generation||JAK1, JAK2||Phase II|
|PF-06651600||2nd generation||JAK3||Phase II||Alopecia areata|
|PF-06700841||2nd generation||JAK1, TYK2||Phase II|
|BMS-986165||2nd generation||TYK2||Phase II||Psoriasis|
|PF-04965842||2nd generation||JAK1||Phase II||Atopic dermatitis|
|Table 1: First and second generation jakinibs, their targets, and their highest level of investigation in dermatologic diseases. Adapted from: Schwartz DM, et al.6 Only those jakinibs that are at least in or post phase II trials have been included. Jakinibs previously investigated in phase II trials in which further development has been discontinued have been excluded from this table.|
The most extensive safety data for JAK inhibitors has come from studies looking at their use in rheumatoid arthritis and myelofibrosis patients. The most common adverse events (AEs) reported in patients treated with tofacitinib are infections (>50%) and gastrointestinal symptoms (>20%), with nasopharyngitis, upper respiratory tract infections, urinary tract infections, and diarrhea being the most common in these categories.7,8 Serious infections have been reported (incidence ratio [IR] = patients with events/100 patient years: 2.7), with the most common being herpes zoster, pneumonia, urinary tract infections, and cellulitis. These rates are similar to those observed with other targeted immunotherapies. Rare but serious AEs include disseminated herpes zoster (IR 0.3), opportunistic infections (IR 0.3), tuberculosis (IR 0.2), and gastrointestinal perforation (IR 0.1).9 A systematic review of patients treated with tofacitinib compared to placebo found that they are significantly more likely to develop laboratory abnormalities including neutropenia, dyslipidemia, elevated creatinine and liver enzyme abnormalities. However, these changes were found to improve over time or return to baseline spontaneously or with discontinuation of the drug.10
The most common AEs reported in patients with myelofibrosis treated with ruxolitinib include anemia (>98%) and thrombocytopenia (>83%). This is not surprising given ruxolitinib’s inhibition of JAK2, which is essential in mediating signals from erythropoietin and thrombopoietin. Other commonly reported AEs include fatigue, diarrhea, ecchymosis, dizziness, headache, and urinary tract infections.11, 12
Both tofacitinib and ruxolitinib cause immunosuppression, leading to a theoretical increased risk of malignancy. An analysis of malignancies occurring in patients treated with tofacitinib found that standardized incidence ratios (SIR) were within the range expected for patients with moderate to severe rheumatoid arthritis, and that the SIR remained stable over time with increasing tofacitinib exposure.13 Overall, the risk of malignancy associated with JAK inhibitors is unclear, and more long-term studies are required.
Clinical Uses in Dermatology
Psoriasis and Psoriatic Arthritis
Many of the cytokines involved in the pathogenesis of psoriasis operate through the JAK-STAT signaling pathway. Most studies in psoriasis have involved tofacitinib, which inhibits the expression of interleukin (IL)-23 and differentiation of T helper type 1 (Th1) cells. IL-23 is a key cytokine that controls Th17 cells, therefore tofacitinib’s downstream effects include reducing Th17 cell differentiation and its production of IL-17.14 Several phase III randomized controlled trials (RCTs) have shown that significantly more patients achieve a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) while on tofacitinib compared with placebo. These patients also demonstrated a dose-dependent improvement of PASI 75 on tofacitinib 10 mg twice daily as compared with 5 mg twice daily.15,16 A phase III non-inferiority trial revealed that tofacitinib 10 mg twice daily was non-inferior to etanercept 50 mg twice weekly.17 More recently, a post hoc analysis of the patients included in the above RCTs demonstrated significant improvements in Nail Psoriasis Severity Index (NAPSI) scores on tofacitinib 10 mg twice daily.18
Two newer JAK inhibitors, baricitinib and solcitinib, have shown promise in psoriasis. A study of baricitinib demonstrated significantly more patients achieved PASI 75 as compared with placebo.19 A multi-center study found solcitinib 400 mg twice daily to have similar efficacy to both tofacitinib and baricitinib, with 57% of patients achieving PASI 75.20 However, further developments in solcitinib have been discontinued.6
Topical JAK inhibitors for mild-moderate psoriasis have also been investigated. Tofacitinib showed variable results in a phase IIa trial. Differences in efficacy were speculated to be due to variability in moisturizing properties of the formulations tested.21 Ruxolitinib (INCB018424) was studied in a non-blinded and nonvehicle- controlled trial and was found to reduce the mean area and severity of psoriatic lesions.22
In December 2017, tofacitinib was approved by the US FDA for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs.23 This was based on the results of two phase III trials, which showed that patients on tofacitinib 5 mg and 10 mg twice daily demonstrated statistically significant improvements in American College of Rheumatology 20 (ACR20) response and change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at 3 months, as compared to placebo.24,25
The pathogenesis of atopic dermatitis is multifactorial, but IL-4 is known to play a pivotal role, signaling through the JAK-STAT pathway via JAK1 and JAK2 to increase the immunity of T helper type 2 cells and enabling further release of various implicated cytokines.26 One small study of tofacitinib in six patients with moderate to severe atopic dermatitis who had failed standard therapy showed promising results. The average Severity Scoring of Atopic Dermatitis (SCORAD) index decreased by 54.8% at 14 weeks of treatment with tofacitinib 5 mg once or twice daily. A significant reduction in pruritus and sleep loss scores was also noted.27 A phase IIa, randomized, double-blind, vehicle-controlled study has been completed using 2% tofacitinib ointment in 69 adult patients with mild to moderate atopic dermatitis. Although the change from baseline in the Eczema Area and Severity Index (EASI) was significantly greater for tofacitinib versus the vehicle after 4 weeks of treatment, further development of this preparation for atopic dermatitis has been discontinued.28
Two new oral agents have recently shown promise in phase II studies. In results presented at the 2017 European Academy of Dermatology and Venereology Congress, PF-04965842 and baricitinib were found to improve clinical and patient-reported outcomes in atopic dermatitis as compared to placebo.29,30
Alopecia areata (AA) is a T cell-mediated autoimmune disease resulting in premature follicular senescence. Interferon-γ (IFN-γ) has been determined to be crucial in the pathogenesis of activating autoreactive T cells, and global transcriptional profiling in AA has identified up-regulation of many interferon-regulated genes and cytokines such as IL-2 and IL-15. Importantly, both IFN-γ and IL-15 signal through JAK1 and JAK3. IL-15 signaling also involves STAT5.31 Systemic ruxolitinib and tofacitinib were shown in a mouse model to stop the IFN-γ gene expression response and subsequent development of AA. Both systemic and topical administration of these drugs have led to reversal of established disease in mice with widespread AA.32
Human studies also demonstrate benefit of jakinibs in AA. A case report published in 2014 featured a patient with concomitant psoriasis and alopecia universalis who experienced complete hair regrowth while on tofacitinib for psoriasis.33 Several other case reports and studies have since been published demonstrating successful treatment of AA, including the associated nail changes.34-36 A retrospective study found that 58% of patients deemed to be potential responders to therapy (meaning those with alopecia totalis or alopecia universalis with duration of disease of 10 years or less, or AA) had greater than 50% change in their Severity of Alopecia Tool (SALT) score while on tofacitinib.37 An open-label trial demonstrated tofacitinib 5 mg twice daily to be efficacious, with 32% of patients reaching 50% or greater improvement in their SALT score. However, with drug discontinuation, relapse occurred within 8.5 weeks.38 A small series of adolescent patients demonstrated hair regrowth in approximately 70% of patients.39
Jakinibs, other than tofacitinib, are also efficacious in AA. A case report from 2015 described a male patient with chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome with concomitant AA. He was enrolled in a trial of baricitinib and experienced complete hair regrowth.40 Ruxolitinib demonstrated sustained, nearcomplete regrowth when used in two patients with AA, and a small open-label trial of 12 patients demonstrated that 75% achieved 92% hair regrowth by the end of treatment. As reported with tofacitinib, however, relapse of hair loss occurred after drug discontinuation.41,42
The pathogenesis of vitiligo remains unclear, although most evidence implicates T-lymphocytes in the destruction of melanocytes. As with AA, IFN-γ likely plays a key role. A case report of a patient with generalized vitiligo treated with tofacitinib 5 mg once daily showed near complete repigmentation after 5 months of treatment.43 An additional case report of a patient with concurrent vitiligo and AA who was treated with ruxolitinib 20 mg twice daily demonstrated both hair regrowth and regained pigment. However, the majority of the pigment that returned during treatment was not sustained after treatment was discontinued.44 More recently, a small open-label trial of topical ruxolitinib 1.5% cream showed significant repigmentation for facial vitiligo, with 76% improvement in Vitiligo Area Scoring Index (VASI) scoring for four patients with facial vitiligo.45
Several case reports have suggested efficacy of jakinibs in refractory dermatomyositis. The first report was of a patient with refractory dermatomyositis on ruxolitinib for concurrent myelofibrosis whose dermatomyositis improved significantly while on ruxolinitib.46 It was unclear, however, if improvement in the dermatomyositis was a direct effect of the JAK inhibitor or an indirect effect through treatment of the malignancy.47 Since then, a case series of three patients treated with tofacitinib found that they had significant improvement in their Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score.48 An additional case report described a patient with dermatomyositis treated with tofacitinib and experienced improvement of her cutaneous disease, muscle strength, and arthritis.49
A retrospective, multi-center survey was conducted in Europe and the US with 95 patients who had been given ruxolitinib as salvage therapy for corticosteroid-refractory graft-versus-host disease (GVHD). In patients with both acute and chronic corticosteroidrefractory GVHD, a cohort known to have poor outcomes, response rates were greater than 80% on ruxolitinib.50 Another retrospective study in patients with severe sclerodermatous chronic GVHD demonstrated partial improvement of skin softness in the majority of cases. However, fewer patients demonstrated a complete response and the response rate overall was lower than the study mentioned previously.51 A retrospective study involving pediatric patients with steroid-refractory acute GVHD showed an overall response rate of 45% to ruxolitinib.52
Several other case reports and preclinical evidence suggest that JAK inhibitors may be useful in the treatment of other inflammatory, autoimmune, and malignant skin conditions. These include cutaneous lupus, cutaneous T-cell lymphoma, melanoma, allergic contact dermatitis, and lichen planus.53-59
JAK inhibitors show promise in the treatment of a wide variety of dermatologic disorders. Compared with other targeted immunosuppressants, jakinibs have similar safety profiles including the rate of serious infection. Longer term studies are needed to assess malignancy risk. Given the interest in this class of drugs and the numerous trials underway, JAK inhibitors have the potential to become widely used in dermatology.
- O’Shea JJ, Holland SM, Staudt LM. JAKs and STATs in immunity, immunodeficiency, and cancer. N Engl J Med. 2013 Jan 10;368(2):161-70.
- Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994 Jun 3;264(5164):1415-21.
- Levy DE, Darnell JE Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002 Sep;3(9):651-62.
- Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005 Mar 19-25;365(9464):1054-61.
- Kontzias A, Kotlyar A, Laurence A, et al. Jakinibs: a new class of kinase inhibitors in cancer and autoimmune disease. Curr Opin Pharmacol. 2012 Aug;12(4):464-70.
- Schwartz DM, Kanno Y, Villarino A, et alJAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017 Dec;16(12):843-62.
- Wollenhaupt J, Silverfield J, Lee EB, et al. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in openlabel, longterm extension studies. J Rheumatol. 2014 May;41(5):837-52.
- Cohen MD, Keystone EC.JAK inhibitors for rheumatoid arthritis. Curr Treatm Opt Rheumatol. 2015 Dec;1(4):305-19.
- Cohen SB, Tanaka Y, Mariette X, et al. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-62.
- He Y, Wong AY, Chan EW, et al. Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis. BMC Musculoskelet Disord. 2013 Oct 18;14:298.
- Arana Yi C, Tam CS, Verstovsek S. Efficacy and safety of ruxolitinib in the treatment of patients with myelofibrosis. Future Oncol. 2015 11(5):719-33.
- Verstovsek S, Mesa RA, Gotlib J, et al. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, doubleblind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017 Feb 22;10(1):55.
- Curtis JR, Lee EB, Kaplan IV, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016 May;75(5):831-41.
- Ghoreschi K, Gadina M. Jakpot! New small molecules in autoimmune and inflammatory diseases. Exp Dermatol. 2014 Jan;23(1):7-11.
- Papp KA, Krueger JG, Feldman SR, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study. J Am Acad Dermatol. 2016 May;74(5):841-50.
- Papp KA, Menter MA, Abe M, et al. Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br J Dermatol. 2015 Oct;173(4):949-61.
- Bachelez H, van de Kerkhof PC, Strohal R, et al. Tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a phase 3 randomised non-inferiority trial. Lancet. 2015 Aug 8;386(9993):552-61.
- Merola JF, Elewski B, Tatulych S, et al. Efficacy of tofacitinib for the treatment of nail psoriasis: Two 52-week, randomized, controlled phase 3 studies in patients with moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2017 Jul;77(1):79-87 e1.
- Papp KA, Menter MA, Raman M, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016 Jun;174(6):1266-76.
- Ludbrook VJ, Hicks KJ, Hanrott KE, et al. Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebocontrolled phase IIa study. Br J Dermatol. 2016 May;174(5):985-95.
- Ports WC, Khan S, Lan S, et al. A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. 2013 Jul;169(1):137-45.
- Punwani N, Burn T, Scherle P, et al. Downmodulation of key inflammatory cell markers with a topical Janus kinase 1/2 inhibitor. Br J Dermatol. 2015 Oct;173(4):989-97.
- Pfizer announces FDA approval of XELJANZ® (tofacitinib) and XELJANZ® XR for the treatment of active psoriatic arthritis [Internet]. Pfizer Pharmaceutical News and Media. Press release dated December 14, 2017. Accessed March 31, 2018.
- Mease P, Hall S, FitzGerald O, et al. Tofacitinib or Adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017 Oct 19;377(16):1537-50.
- Gladman D, Rigby W, Azevedo VF, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017 Oct 19;377(16):1525-36.
- Bao L, Shi VY, Chan LS. IL-4 regulates chemokine CCL26 in keratinocytes through the Jak1, 2/Stat6 signal transduction pathway: Implication for atopic dermatitis. Mol Immunol. 2012 Feb;50(1-2):91-7.
- Levy LL, Urban J, King BA. Treatment of recalcitrant atopic dermatitis with the oral Janus kinase inhibitor tofacitinib citrate. J Am Acad Dermatol. 2015 Sep;73(3):395-9.
- Bissonnette R, Papp KA, Poulin Y, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016 Nov;175(5):902-11.
- Baricitinib meets primary endpoint in phase 2 study of patients with moderateto-severe atopic dermatitis [Internet]. Eli Lilly and Company. Press release dated September 14, 2017.
- JAK inhibitors for atopic dermatitis might hit JAK-pot [Internet]. Mdedge.com. Published: December 12, 2017. Available from: https://www.mdedge.com/edermatologynews/article/154135/atopic-dermatitis/jak-inhibitors-atopicdermatitis-might-hit-jak-pot. Accessed March 31, 2018.
- Gilhar A, Schrum AG, Etzioni A, et al. Alopecia areata: Animal models illuminate autoimmune pathogenesis and novel immunotherapeutic strategies. Autoimmun Rev. 2016 Jul;15(7):726-35.
- 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 Sep;20(9):1043-9.
- 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 Dec;134(12):2988-90.
- Gupta AK, Carviel JL, Abramovits W. Efficacy of tofacitinib in treatment of alopecia universalis in two patients. J Eur Acad Dermatol Venereol. 2016 Aug;30(8):1373-8.
- Mrowietz U, Gerdes S, Glaser R, et al. 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 Feb 8;97(2):283-4.
- Ferreira SB, Scheinberg M, Steiner D, et al. Remarkable improvement of nail changes in alopecia areata universalis with 10 months of treatment with tofacitinib: a case report. Case Rep Dermatol. 2016 Sep-Dec;8(3):262-6.
- Liu LY, Craiglow BG, Dai F, et al. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017 Jan;76(1):22-8.
- 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 Sep 22;1(15):e89776
- Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017 Jan;76(1):29-32.
- Jabbari A, Dai Z, Xing L, et al. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine. 2015 Apr;2(4):351-5.
- Vandiver A, Girardi N, Alhariri J, et al. Two cases of alopecia areata treated with ruxolitinib: a discussion of ideal dosing and laboratory monitoring. Int J Dermatol. 2017 Aug;56(8):833-5.
- 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 Sep 22;1(15):e89790.
- Craiglow BG, King BA. Tofacitinib citrate for the treatment of vitiligo: a pathogenesis-directed therapy. JAMA Dermatol. 2015 Oct;151(10):1110-2.
- Harris JE, Rashighi M, Nguyen N, et al. Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol. 2016 Feb;74(2):370-1.
- Rothstein B, Joshipura D, Saraiya A, et al. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J Am Acad Dermatol. 2017 Jun;76(6):1054-60 e1.
- Hornung T, Janzen V, Heidgen FJ, et al. Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med. 2014 Dec 25;371(26):2537-8.
- Selva-O’Callaghan A, Trallero-Araguas E, Labrador-Horrillo M. More on remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med. 2015 Mar 26;372(13):1273-4.
- Kurtzman DJ, Wright NA, Lin J, et al. Tofacitinib citrate for refractory cutaneous dermatomyositis: an alternative treatment. JAMA Dermatol. 2016 Aug 1;152(8):944-5.
- Paik JJ, Christopher-Stine L. A case of refractory dermatomyositis responsive to tofacitinib. Semin Arthritis Rheum. 2017 Feb;46(4):e19.
- Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015 Oct;29(10):2062-8.
- Hurabielle C, Sicre de Fontbrune F, Moins-Teisserenc H, et al. Efficacy and tolerance of ruxolitinib in refractory sclerodermatous chronic graft-versus-host disease. Br J Dermatol. 2017 Nov;177(5):e206-e8.
- Khandelwal P, Teusink-Cross A, Davies SM, et al. Ruxolitinib as salvage therapy in steroid-refractory acute graft-versus-host disease in pediatric hematopoietic stem cell transplant patients. Biol Blood Marrow Transplant. 2017 Jul;23(7):1122-7.
- Wenzel J, van Holt N, Maier J, et al. JAK1/2 Inhibitor ruxolitinib controls a case of chilblain lupus erythematosus. J Invest Dermatol. 2016 Jun;136(6):1281-3.
- Perez C, Gonzalez-Rincon J, Onaindia A, et al. Mutated JAK kinases and deregulated STAT activity are potential therapeutic targets in cutaneous T-cell lymphoma. Haematologica. 2015 Nov;100(11):e450-3.
- McGirt LY, Jia P, Baerenwald DA, et al. Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides. Blood. 2015 Jul 23;126(4):508-19.
- Li MY, Tian Y, Shen L, et al. 3-O-methylthespesilactam, a new small-molecule anticancer pan-JAK inhibitor against A2058 human melanoma cells. Biochem Pharmacol. 2013 Nov 15;86(10):1411-8.
- Maenhout SK, Du Four S, Corthals J, et al. AZD1480 delays tumor growth in a melanoma model while enhancing the suppressive activity of myeloid-derived suppressor cells. Oncotarget. 2014 Aug 30;5(16):6801-15.
- Fukuyama T, Ehling S, Cook E, et al. 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 Sep;354(3):394-405.
- Di Lernia V. Targeting the IFN-gamma/CXCL10 pathway in lichen planus. Med Hypotheses. 2016 Jul;92:60-1.