INTRODUCTION

Janus kinase (JAK) inhibitors represent a groundbreaking class of immunomodulatory agents that target the JAK–STAT signaling pathway, a critical mediator of cytokine-driven inflammatory processes [1]. Originally developed for rheumatologic conditions such as rheumatoid arthritis, these small molecules have gained increasing traction in dermatology due to their ability to dampen multiple pro-inflammatory cytokine signals simultaneously [2], making them highly versatile therapeutic agents.

Emerging evidence underscores the efficacy of JAK inhibitors across a spectrum of dermatologic diseases, including atopic dermatitis, alopecia areata, psoriasis, and vitiligo [3]. Their ability to inhibit various JAK family members (JAK1, JAK2, JAK3, TYK2) provides mechanistic flexibility and has fueled both systemic and topical clinical developments [4].

However, alongside their therapeutic promise, growing safety concerns have arisen—particularly in light of regulatory mandates like FDA black box warnings. These pertain to risks of serious infections, venous thromboembolism (VTE), major adverse cardiovascular events (MACE), and malignancies, initially identified in rheumatologic populations but raising caution across dermatologic uses [5,6]. Notably, some dermatology-specific data suggest that adverse event rates may be lower in younger and otherwise healthy populations, although vigilance remains essential [7].

Given the expanding clinical indications and mounting safety considerations, a comprehensive synthesis is needed to guide evidence-based, individualized use of JAK inhibitors in dermatology. This review addresses that need by integrating mechanistic insights, clinical efficacy across multiple indications, safety controversies, and practical strategies for risk assessment and management.

MECHANISTIC BASIS OF JAK INHIBITION

The Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway is a pivotal intracellular signaling cascade regulating immune responses, hematopoiesis, and skin inflammation [8]. Dysregulation of this pathway has been implicated in several dermatologic diseases, particularly those driven by Th1, Th2, and Th17 cytokines such as interferons, interleukins (IL-4, IL-13, IL-22, IL-23), and granulocyte–macrophage colony-stimulating factor [9].

The JAK family consists of four non-receptor tyrosine kinases: JAK1, JAK2, JAK3, and TYK2. Each associates with specific cytokine receptors and mediates phosphorylation of STAT proteins, which then translocate to the nucleus to drive transcription of inflammatory genes [10]. Selective inhibition of different JAKs allows modulation of distinct immunologic pathways:

This mechanistic diversity underpins the development of both broad-spectrum and selective JAK inhibitors. For instance, baricitinib (JAK1/2) and upadacitinib (selective JAK1) are orally available agents approved for atopic dermatitis and alopecia areata, while deucravacitinib, a selective TYK2 inhibitor, has demonstrated efficacy in psoriasis [12].

Importantly, the dual ability of JAK inhibitors to suppress multiple cytokine pathways provides clinical advantages in polygenic diseases like atopic dermatitis but also raises concerns about off-target immunosuppression and long-term safety [13]. This balance between broad immunomodulation and adverse event risk remains a core controversy in their clinical adoption.

EXPANDING INDICATIONS IN DERMATOLOGY

Since their initial approval in rheumatology, JAK inhibitors have rapidly expanded into dermatology, demonstrating efficacy across a range of immune-mediated skin disorders. Multiple agents-oral and topical-are now approved or in late-phase development for dermatologic use [14].

Currently approved JAK inhibitors, their indications, and pivotal trials are summarized in Table 1 [1–14].

ATOPIC DERMATITIS (AD)

Atopic dermatitis has been the leading dermatologic indication for JAK inhibitors. Clinical trials of abrocitinib, upadacitinib, and baricitinib have demonstrated rapid improvements in Eczema Area and Severity Index (EASI) and itch scores compared to placebo [15]. Both abrocitinib and upadacitinib are now FDA-approved for moderate-to-severe AD, with real-world studies confirming their effectiveness and tolerability [16]. Topical ruxolitinib cream has also gained approval for mild-to-moderate AD, providing a targeted option with limited systemic exposure [17].

ALOPECIA AREATA (AA)

Alopecia areata has seen transformative progress with JAK inhibitors. Baricitinib became the first FDA-approved systemic therapy for severe AA in 2022, followed by ritlecitinib in 2023 and deuruxolitinib in 2024 [18]. Phase 3 trials demonstrated significant hair regrowth, with 30–40% of patients achieving a Severity of Alopecia Tool (SALT) score ≤20 at 36 weeks [19]. These approvals have marked a paradigm shift in management of severe AA, which previously lacked effective systemic treatments.

VITILIGO

The approval of topical ruxolitinib in 2022 for nonsegmental vitiligo represents the first FDA-approved therapy targeting repigmentation [20]. Clinical trials have shown significant improvement in facial Vitiligo Area Scoring Index (F-VASI) scores, with durable repigmentation observed in long-term extension studies [21]. This milestone highlights the potential of JAK inhibition to address long-standing unmet needs in pigmentary disorders.

PSORIASIS AND PSORIATIC ARTHRITIS

Although biologics targeting IL-17 and IL-23 remain first-line for psoriasis, JAK inhibitors—particularly deucravacitinib, a selective TYK2 inhibitor—have emerged as promising oral options [22]. Phase 3 trials (POETYK PSO-1 and PSO-2) demonstrated durable efficacy comparable to biologics, with a favorable safety profile [23]. JAK inhibitors are also being explored in psoriatic arthritis, with encouraging preliminary results [24].

OTHER EMERGING INDICATIONS

Early studies suggest potential roles for JAK inhibitors in lichen planus, hidradenitis suppurativa, cutaneous lupus erythematosus, and dermatomyositis, though these remain investigational [25,26]. Their broad immunomodulatory capacity makes them attractive candidates for diseases driven by multiple cytokine pathways.

SAFETY PROFILE AND CONCERNS

While JAK inhibitors have demonstrated remarkable efficacy in dermatology, safety remains the most debated issue. Regulatory agencies, including the U.S. FDA and EMA, have emphasized caution by issuing black box warnings based largely on rheumatology trials [27]. Key areas of concern include infections, malignancy, cardiovascular events, venous thromboembolism (VTE), and laboratory abnormalities.

Common adverse events observed with JAK inhibitors, categorized by system involvement, are summarized in Table 2 [15–26].

INFECTIONS

The most frequent adverse events across dermatologic indications are infections, particularly upper respiratory tract infections and herpes zoster reactivation [27]. Vaccination against varicella-zoster virus is recommended prior to initiating therapy, especially in high-risk populations [28]. Opportunistic infections remain rare in dermatology cohorts compared to rheumatology populations [29].

MALIGNANCY RISK

Long-term safety studies in rheumatology, particularly in rheumatoid arthritis (RA), have raised concerns about malignancy risk associated with JAK inhibitors. The ORAL Surveillance trial reported an increased incidence of malignancies, including lung cancer and lymphoma, in patients treated with tofacitinib compared to TNF inhibitors, especially in older adults with cardiovascular risk factors [30]. These findings prompted regulatory agencies to issue black box warnings for all approved JAK inhibitors, regardless of indication, fueling significant caution in dermatology.

In contrast, data from dermatology-specific trials have not consistently demonstrated a heightened risk of malignancy. Long-term extension studies of JAK inhibitors in atopic dermatitis and psoriasis cohorts have thus far reported malignancy rates comparable to background population rates or to those observed with biologic therapies [31]. The discrepancy may be explained by differences in patient characteristics: RA cohorts typically include older patients with multiple comorbidities and prior exposure to immunosuppressants, whereas dermatology populations are often younger and healthier. Nevertheless, the relatively short duration of dermatology trials (often under 3 years) limits the ability to detect late-emerging malignancy signals.

At present, the absolute risk of malignancy with JAK inhibitors in dermatology appears low, particularly in younger patients without significant comorbidities. However, vigilance remains warranted, particularly in populations with known cancer risk factors such as heavy smoking or prior history of malignancy. Active surveillance through registries and post-marketing studies will be critical to clarify long-term risks. Until more definitive data are available, dermatologists are advised to individualize treatment decisions, weigh risks against therapeutic benefit, and ensure appropriate cancer screening in patients receiving prolonged JAK inhibitor therapy [32,33].

CARDIOVASCULAR AND THROMBOEMBOLIC EVENTS

Concerns regarding major adverse cardiovascular events (MACE) and VTE originated from the ORAL Surveillance trial in rheumatoid arthritis [34]. Subsequent dermatology trials have not demonstrated a clear signal, though patients with pre-existing cardiovascular risk factors may be more vulnerable [35]. Current guidelines recommend careful risk stratification prior to prescribing JAK inhibitors in patients with cardiovascular comorbidities [36].

LABORATORY ABNORMALITIES

JAK inhibitors are associated with dose-dependent laboratory changes, including elevations in lipid levels, cytopenias, and elevated liver enzymes [37]. Most changes are mild and reversible, but routine monitoring is recommended during treatment [38].

PEDIATRIC AND LONG-TERM SAFETY

JAK inhibitors have recently been approved for pediatric use in atopic dermatitis and alopecia areata. Initial studies suggest a favorable safety profile, though long-term data are still lacking [39]. Registry-based surveillance will be essential to clarify risks over time [40].

CURRENT CONTROVERSIES

Despite their therapeutic promise, Janus kinase (JAK) inhibitors continue to generate significant debate within dermatology. One major controversy revolves around their comparative efficacy to established biologics such as IL-4/IL-13 or IL-17/IL-23 inhibitors. While JAK inhibitors often show rapid onset of action and convenient oral administration, some trials suggest biologics may offer superior long-term disease control in conditions like psoriasis and atopic dermatitis [41,42]. Moreover, questions remain regarding their optimal positioning in treatment algorithms—should they be reserved for refractory cases, or considered earlier in therapy given their broad immunomodulatory effects? These uncertainties highlight the need for head-to-head trials and real-world effectiveness data to better define their clinical niche [43,44].

Long-term safety concerns represent another central controversy. Regulatory agencies, including the FDA and EMA, have issued warnings regarding elevated risks of major adverse cardiovascular events, malignancies, and venous thromboembolism associated with JAK inhibitor use, particularly in older patients and those with comorbidities. While some dermatology-focused trials report acceptable safety profiles, extrapolation from rheumatology data has fueled caution and more restrictive labeling. In addition, economic considerations—such as high costs compared with conventional immunosuppressants-further complicate access and insurance coverage [45]. These overlapping debates underscore the balance dermatologists must strike between innovation, safety, and affordability when integrating JAK inhibitors into practice.

BALANCING EFFICACY AND SAFETY

While JAK inhibitors offer rapid and robust responses in conditions such as atopic dermatitis and alopecia areata, concerns regarding malignancy, infection, and cardiovascular risk continue to influence prescribing decisions [46]. Dermatologists are challenged to weigh the benefit of rapid symptom control against the uncertain long-term safety profile [47].

REGULATORY WARNINGS VS. REAL-WORLD DATA

The FDA’s 2021 black box warnings were based primarily on rheumatoid arthritis populations with significant comorbidities [48]. Real-world dermatology studies suggest lower rates of severe adverse events, particularly in younger, otherwise healthy patients [49]. This discrepancy fuels debate over whether dermatology patients are being over-cautioned compared to their actual risk.

POSITIONING RELATIVE TO BIOLOGICS

Another key controversy is the role of JAK inhibitors compared to established biologics such as dupilumab, IL-17 inhibitors, and IL-23 inhibitors [50]. While JAK inhibitors provide the convenience of oral administration and rapid onset of action, biologics have a longer track record of safety. Determining their relative placement in treatment algorithms remains unsettled [51,52].

COST AND ACCESSIBILITY

JAK inhibitors are often priced comparably to biologics, raising questions about cost-effectiveness [53]. Insurance restrictions and prior authorization requirements further complicate access, and disparities in global availability may limit their widespread adoption [54].

MONITORING BURDEN

The need for ongoing laboratory monitoring (lipids, CBC, liver enzymes) differentiates JAK inhibitors from biologics, which often require less intensive surveillance [55]. Some experts argue this may limit long-term patient adherence and increase healthcare costs, while others emphasize the manageable nature of monitoring compared to the benefits [56].

PRACTICAL CONSIDERATIONS

As JAK inhibitors enter routine dermatologic practice, clinicians must address several practical issues, including patient selection, monitoring strategies, and integration with existing therapies.

PATIENT SELECTION AND RISK STRATIFICATION

Optimal use of JAK inhibitors requires careful assessment of individual patient risk factors. They are particularly well-suited for patients with severe, refractory disease who fail or cannot tolerate biologics [57]. Patients with high cardiovascular risk, prior malignancy, or recurrent infections may be better suited to alternative therapies [58]. Shared decision-making, incorporating patient preference, disease burden, and comorbidity profile, is essential [59].

BASELINE AND ONGOING MONITORING

Laboratory evaluation at baseline typically includes CBC, liver function tests, renal function, and lipid profile [60]. Ongoing monitoring every 8–12 weeks is recommended during the first year, with individualized adjustment thereafter [61]. Vaccination against herpes zoster should be considered prior to initiation [62].

PRESCRIBING PATTERNS AND CLINICAL USE

In practice, dermatologists often favor JAK inhibitors for patients with rapid disease progression or intolerable pruritus, given their fast onset of action compared to biologics [63]. Oral administration provides an additional convenience advantage, which can improve adherence in select populations [64].

COMBINATION AND SEQUENTIAL THERAPY

Combination strategies are an area of active exploration. Case reports suggest that combining JAK inhibitors with topical corticosteroids, phototherapy, or biologics may enhance efficacy while potentially reducing required systemic doses [65]. However, robust data are limited, and safety of long-term combination therapy remains uncertain [66].

SPECIAL POPULATIONS

Use in children and adolescents has expanded following recent FDA approvals for atopic dermatitis and alopecia areata, though clinicians must remain vigilant given limited long-term safety data [67]. In older adults, risk–benefit assessments are particularly important due to higher baseline cardiovascular and malignancy risks [68].

Key similarities and differences between JAK inhibitors and biologics in dermatology are summarized in Table 3 [27–68].

FUTURE DIRECTIONS

The field of JAK inhibition in dermatology continues to evolve rapidly, with several promising avenues under investigation.

DEVELOPMENT OF MORE SELECTIVE INHIBITORS

Newer agents aim to maximize efficacy while minimizing adverse effects by selectively targeting specific JAK isoforms. TYK2 inhibitors such as deucravacitinib demonstrate encouraging efficacy in psoriasis with a more favorable safety profile compared to broader JAK inhibitors [69]. Next-generation selective JAK1 inhibitors are also being developed for atopic dermatitis and alopecia areata [70].

BIOMARKERS FOR RESPONSE AND SAFETY

A major unmet need in the use of JAK inhibitors for dermatologic diseases is the identification of reliable biomarkers that can predict both therapeutic response and susceptibility to adverse events. Current clinical decision-making largely relies on trial-and-error, as no validated markers are routinely available to stratify patients. Transcriptomic and proteomic profiling studies have begun to shed light on immune signatures that correlate with favorable responses, such as modulation of interferon-regulated genes and downregulation of Th2 cytokine pathways [71]. These molecular patterns may help identify subsets of patients with atopic dermatitis, psoriasis, or alopecia areata who are most likely to achieve durable remission with JAK inhibition.

Equally important are biomarkers for safety, given the concerns regarding cardiovascular, thrombotic, and malignancy risks associated with long-term JAK inhibitor therapy. Early data suggest that baseline cardiovascular risk factors, systemic inflammatory markers (e.g., C-reactive protein, IL-6), and even genetic polymorphisms in JAK/STAT pathway genes could influence susceptibility to adverse outcomes [72]. Integrating these findings into clinical algorithms represents a key step toward personalized medicine, where treatment choice and monitoring strategies are tailored to individual risk–benefit profiles. Such advances may not only improve efficacy and safety outcomes but also support regulatory decision-making and payer acceptance of JAK inhibitors in dermatology.

LONG-TERM SAFETY DATA AND REGISTRIES

Although clinical trial data support short- to mid-term safety, uncertainties remain regarding malignancy risk, cardiovascular outcomes, and infection rates in long-term use. Dermatology-specific registries are being established to capture real-world outcomes over extended periods [73]. These efforts will be essential in refining monitoring protocols and informing regulatory guidance [74].

EXPANSION INTO RARE DERMATOSES

Beyond their established use in atopic dermatitis, alopecia areata, vitiligo, and psoriasis, JAK inhibitors are now being explored in a range of rarer and often treatment-refractory dermatoses. Pilot studies and early-phase clinical reports suggest promising activity in hidradenitis suppurativa (HS), where dysregulated innate immunity and aberrant cytokine signaling may be partially mediated through the JAK/STAT pathway [75]. Initial case series with tofacitinib and upadacitinib demonstrated reductions in abscess formation and symptomatic improvement in patients resistant to biologics, highlighting a potential new avenue for disease control. However, larger, controlled trials are necessary to validate efficacy and clarify whether JAK inhibition should complement or compete with existing anti-TNF and IL-17 strategies.

Similarly, in mucocutaneous lichen planus, JAK inhibitors have shown potential in reducing keratinocyte apoptosis and inflammation mediated by IFN-g signaling. Several case reports describe rapid improvement with tofacitinib or baricitinib in patients unresponsive to corticosteroids or calcineurin inhibitors, offering hope for a condition with limited systemic options [76]. Cutaneous lupus erythematosus (CLE) also represents a promising target given the central role of type I interferon signaling. Early data indicate that JAK blockade may attenuate cutaneous activity and reduce flare frequency, although safety concerns regarding immunosuppression in a population already predisposed to systemic involvement remain significant [77].

Emerging reports also point to benefits in dermatomyositis, where JAK inhibitors may reduce interferon-driven skin and muscle inflammation. Case series document improvements in cutaneous rash severity and muscle strength with ruxolitinib or baricitinib, raising the possibility of a disease-modifying approach in an area long dominated by broad immunosuppressants [78]. If validated through larger multicenter trials, these findings could broaden the therapeutic armamentarium in dermatology, delivering targeted therapies to patient groups with few existing options. Importantly, further mechanistic studies are needed to understand differential responses across rare dermatoses and to optimize patient selection.

Beyond common indications such as atopic dermatitis and alopecia areata, JAK inhibitors are also being explored in rare dermatoses, with early clinical signals summarized in Table 4 [69–78].

COMBINATION AND SEQUENTIAL THERAPIES

Future therapeutic strategies are increasingly considering the sequential or combined use of JAK inhibitors with other systemic agents, particularly biologics. The rationale is that integrating targeted cytokine blockade (e.g., IL-4/IL-13 or IL-17/23 inhibition) with broader JAK/STAT modulation could enhance efficacy in refractory patients or accelerate remission in severe disease [79]. Pilot case reports in atopic dermatitis and psoriasis suggest that switching between biologics and JAK inhibitors, or using them in sequence, may recapture response after loss of efficacy to monotherapy. However, systematic evaluation is lacking, and optimal sequencing algorithms remain undefined.

Another potential avenue is the use of carefully monitored combination regimens. For example, combining JAK inhibitors with biologics or conventional immunosuppressants (e.g., methotrexate, cyclosporine) may allow dose reduction of each agent, potentially minimizing toxicity while maximizing efficacy [80]. Such regimens could be particularly valuable in complex or multisystem disease, such as psoriatic arthritis with cutaneous involvement or overlap syndromes. Nonetheless, the theoretical risk of additive immunosuppression-including infection, malignancy, and cardiovascular complications-necessitates rigorous clinical trials and long-term registry data before such strategies can be safely implemented in practice.

CONCLUSION

JAK inhibitors have rapidly emerged as transformative therapies in dermatology, reshaping management strategies for conditions such as atopic dermatitis, alopecia areata, vitiligo, and psoriasis. Their ability to modulate multiple cytokine pathways offers advantages over targeted biologics, particularly in terms of rapid onset of action and oral administration [81].

Nevertheless, safety concerns remain central to clinical decision-making. While real-world dermatology data suggest lower risks compared to rheumatology populations, uncertainties regarding long-term risks of malignancy, cardiovascular disease, and infection persist [82]. Careful patient selection, risk stratification, and ongoing monitoring are therefore essential in routine practice [83].

Looking ahead, the future of JAK inhibitors lies in the development of selective isoform inhibitors, integration of biomarker-driven personalized medicine, and the expansion of indications to rarer dermatoses. Long-term registries and post-marketing surveillance will be critical in establishing their true safety profile [84,85].

Ultimately, JAK inhibitors represent both a breakthrough and a challenge: they hold immense potential to improve patient outcomes but demand cautious, evidence-based application guided by evolving data. Dermatologists must remain vigilant, balancing efficacy with safety while leveraging these agents to meet diverse patient needs [86–88].

REFERENCES

1.Strober B, Ryan C, van der Walt J. Efficacy and safety of tofacitinib for plaque psoriasis:pooled analysis of phase 3 trials. J Am Acad Dermatol. 2016;74-100.

2.Samuel C. A review on the safety of using JAK inhibitors in dermatology patients. Ther Adv Drug Saf. 2023;14-20.

3.US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors. FDA Drug Safety Communication. 2021 [cited 2025 Sep 7]. 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

4.Solimani F, Meier K, Ghoreschi K. Emerging topical and systemic JAK inhibitors in dermatology. Front Immunol. 2019;10:2847.

5.King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386:1687-99.

6.Zhang X, Ye Y, Sun W, Sheng Y, Kinoshita-Ise M, Ito T, et al. Efficacy and safety of ritlecitinib in Asian patients with alopecia areata:A subgroup analysis of the ALLEGRO phase 2b/3 trial. J Dermatol. 2025;52:603-614.

7.Wambier CG, King B, Guttman-Yassky E, Rossi A, Jimenez JJ, Shapiro J, et al. Deuruxolitinib for alopecia areata:efficacy from pivotal phase 3 trials. J Am Acad Dermatol. 2024;90:623-34.

8.Silverberg JI, Simpson EL, Thyssen JP, Bieber T, Katoh N, De Bruin-Weller M, et al. Abrocitinib versus placebo or dupilumab for moderate-to-severe atopic dermatitis (JADE COMPARE):a phase 3 randomized trial. Lancet. 2021;397:738-48.

9.Reich K, Papp KA, Blauvelt A, Bieber T, De Bruin-Weller M, Soong W, et al. Upadacitinib in patients with atopic dermatitis:results from Measure Up 1 and 2. Lancet. 2021;397:2151-68.

10.Bieber T, Katoh N, Simpson EL, Silverberg JI, Thaçi D, Nakahara T, et al. Safety of upadacitinib and abrocitinib in atopic dermatitis:pooled analysis. J Allergy Clin Immunol.2022;149:744-56.

11.US Food and Drug Administration. Deuruxolitinib [package insert]. FDA;2024. Available from:https://www.accessdata.fda.gov

12.O’Shea JJ, Schwartz DM, Villarino AV, Gadina M, McInnes IB, Laurence A. The JAK–STAT pathway:impact on disease and therapeutic intervention. Annu Rev Med. 2015;66:311-28.

13.Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O’Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16:843-62.

14.Damsky W, King BA. JAK inhibitors in dermatology:the promise of a new drug class. J Am Acad Dermatol. 2017;76:736-44.

15.Miot HA, Ferreira JC, Teixeira DA. JAK-STAT pathway inhibitors in dermatology:an update. An Bras Dermatol. 2023;98:247-55.

16.Ytterberg SR, Bhatt DL, Mikuls TR, Koch GG, Fleischmann R, Rivas JL, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-26.

17.Soria A, Bewley A, Guttman-Yassky E. Safety of JAK inhibitors in dermatology:lessons from practice. Br J Dermatol. 2023;188:674-83.

18.Blauvelt A, Silverberg JI, Lynde CW, Bieber T, Simpson EL, Thaçi D, et al. Mechanisms of action of selective JAK1 inhibitors in atopic dermatitis. J Dermatolog Treat. 2022;33:3173-81.

19.Chimalakonda A, Lee CH, Kavanaugh A. Selective TYK2 inhibition in autoimmune diseases:rationale and clinical data. Curr Opin Rheumatol. 2021;33:225-32.

20.Simpson EL, De Bruin-Weller M, Silverberg JI, Deleuran M, Kataoka Y, Lacour JP, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis:results from two phase 3 trials. Lancet. 2020;396:151-62.

21.Armstrong AW, Gooderham M, Warren RB, Papp KA, Strober B, Thaçi D, et al. Efficacy and safety of deucravacitinib in moderate-to-severe plaque psoriasis (POETYK PSO-1 and PSO-2). N Engl J Med. 2022;387:130-41.

22.Ghoreschi K, Gadina M, O’Shea JJ. JAKpot:selective and non-selective JAK inhibitors in immunology and beyond. Nat Rev Immunol. 2009;9:491-503.

23.Gooderham MJ, Forman SB, Bissonnette R, Szepietowski JC, Ferris LK, An J, et al. The expanding role of Janus kinase inhibitors in dermatology. Br J Dermatol. 2023;189:12-23.

24.Silverberg JI, Simpson EL, Thyssen JP, Bieber T, Katoh N, De Bruin-Weller M, et al. Abrocitinib versus placebo or dupilumab for moderate-to-severe atopic dermatitis (JADE COMPARE):a phase 3 randomized trial. Lancet. 2021;397:738-48.

25.Reich K, Papp KA, Blauvelt A, Bieber T, De Bruin-Weller M, Soong W, et al. Upadacitinib in patients with atopic dermatitis:results from Measure Up 1 and 2. Lancet. 2021;397:2151-68.

26.Yew YW, Puar THK, Thng S, Pang SM, Chan SL, Tey HL, et al. Real-world effectiveness and safety of abrocitinib in moderate-to-severe atopic dermatitis:a multicenter cohort study. J Am Acad Dermatol. 2023;89:56-65.

27.Papp K, Szepietowski JC, Kircik L, Toth D, Forman SB, Aschoff R, et al. Ruxolitinib cream for the treatment of atopic dermatitis:results from two phase 3 trials. J Am Acad Dermatol. 2021;85:863-72.

28.King B, Ohyama M, Kwon O, Zlotogorski A, Ko J,Mesinkovska NA, et al. Two phase 3 trials of baricitinib for alopecia areata. N Engl J Med. 2022;386:1687-99.

29.Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise J, Ramot Y, Ziv M,et al. Efficacy and safety of ritlecitinib in alopecia areata:ALLEGRO phase 2b/3 results. J Invest Dermatol. 2023;143:784-93.

30.Wambier CG, King B, Guttman-Yassky E, Rossi A, Jimenez JJ, Shapiro J, et al. Deuruxolitinib for alopecia areata:efficacy from pivotal phase 3 trials. J Am Acad Dermatol. 2024;90:623-34.

31.Rosmarin D, Passeron T, Pandya AG, Grimes P, Harris JE, Desai S,et al. Ruxolitinib cream for vitiligo:results from TRuE-V1 and TRuE-V2 phase 3 trials. Lancet. 2022;400:2222-34.

32.Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G, Clynes R,et al. Rapid skin repigmentation on oral ruxolitinib in vitiligo. N Engl J Med. 2016;374:55-62.

33.Liu LY, Strassner JP, Refat MA, Harris JE. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure. J Am Acad Dermatol. 2017;77:675-82.

34.Craiglow BG, King BA. Tofacitinib for the treatment of vitiligo:a pathogenesis-directed therapy. JAMA Dermatol. 2015;151:1110-2.

35.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.

36.Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME, et al. Treatment of atopic dermatitis with ruxolitinib cream (TRuE-AD1 and TRuE-AD2):results from two randomised, double-blind, vehicle-controlled phase 3 trials. Lancet. 2020;396:255-66.

37.Papp KA, Krueger JG, Thaçi D, Langley RG, Hesse D, Rodrigues J, et al. Efficacy and safety of baricitinib in patients with moderate-to-severe psoriasis:results from a phase 2 trial. Br J Dermatol. 2016;174:1266-76.

38.Mease PJ, Smolen JS, Behrens F, Nash P, Liu Y, Li W, et al. A head-to-head comparison of upadacitinib and adalimumab for psoriatic arthritis:SELECT-PsA 1 trial. Ann Rheum Dis. 2021;80:1415-26.

39.McInnes IB, Anderson JK, Magrey M, Merola JF, Liu Y, Kishimoto M, et al. Trial of upadacitinib and adalimumab for psoriatic arthritis. N Engl J Med. 2021;384:1227-39.

40.Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, et al;OPT Pivotal 1 and OPT Pivotal 2 investigators. 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;173:949-61.

41.Bissonnette R, Iversen L, Sofen H, Griffiths CE, Foley P, Romiti R, et al. Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis:results from a randomized controlled trial. Br J Dermatol. 2015;172:1395-406.

42.Gooderham M, Forman S, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and safety of ruxolitinib cream for the treatment of psoriasis:results from a phase 2 trial. J Am Acad Dermatol. 2019;80:1142-8.

43.Dummer R, Ascierto PA, Gogas HJ, Arance AM, MandalàM, Liszkay G, et al. Ruxolitinib for advanced melanoma:results of a multicenter phase 2 trial. J Clin Oncol. 2020;38:2010-9.

44.Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424:therapeutic implications for the treatment of myeloproliferative neoplasms. Blood. 2010;115:3109-17.

45.Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366:799-807.

46.Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366:787-98.

47.McLornan DP, Pope JE, Gotlib J, Harrison CN. Current and future status of JAK inhibitors. Lancet. 2021;398:803-16.

48.Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, et al. Secukinumab in plaque psoriasis:results of two phase 3 trials. N Engl J Med. 2014;371:326-38.

49.Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375:345-56.

50.Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, et al. Adalimumab, an anti–tumor necrosis factor a monoclonal antibody, for the treatment of psoriatic arthritis:results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005;52:3279-89.

51.Ogdie A, Coates LC, Gladman DD. Treatment guidelines in psoriatic arthritis. Rheumatology (Oxford). 2020;59:37-46.

52.Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med. 2017;376:957-70.

53.Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, et al. Anti–IL-23A mAb guselkumab in moderate-to-severe psoriasis. N Engl J Med. 2015;373:136-44.

54.Griffiths CEM, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER trials). N Engl J Med. 2015;373:134-44.

55.Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis:a review. JAMA. 2020;323:1945-60.

56.Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, van Voorhees AS, et al. Psoriasis and comorbid diseases:epidemiology. J Am Acad Dermatol. 2017;76:377-90.

57.Guttman-Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis:results from four phase 3 trials. J Am Acad Dermatol. 2019;80:913-21.

58.Bieber T, Thyssen JP, Reich K, Simpson EL, Katoh N, de Bruin-Weller M, et al. Pooled safety analysis of abrocitinib in moderate-to-severe atopic dermatitis. Allergy. 2022;77:2536-47.

59.Simpson EL, Forman S, Silverberg JI, Bieber T, Zirwas M, Wilke A, et al. Efficacy of upadacitinib in adolescents and adults with atopic dermatitis:measure up 1 and 2 trials. J Allergy Clin Immunol. 2021;148:513-27.

60.Kim BS, Howell MD, Sun K, Nasir A, Kuligowski ME, Vinh DC, et al. Long-term efficacy and safety of ruxolitinib cream for atopic dermatitis (TRuE-AD1/2 LTE). Br J Dermatol. 2022;187:741-9.

61.Strober B, Ryan C, van der Walt J. Efficacy and safety of tofacitinib for plaque psoriasis:pooled analysis of phase 3 trials. J Am Acad Dermatol. 2016;74:100-9.

62.Lebwohl M, Papp K, Bagel J. Long-term safety experience of tofacitinib in plaque psoriasis. Br J Dermatol. 2017;177:948-61.

63.Blauvelt A, Papp K, Griffiths CEM. Efficacy and safety of abrocitinib for psoriasis:results from a phase 2 trial. J Am Acad Dermatol. 2020;82:1301-9.

64.Mease PJ, Helliwell PS, Gladman DD. Tofacitinib in psoriatic arthritis:two phase 3 randomized controlled trials. N Engl J Med. 2017;377:1537-50.

65.Mease PJ, van der Heijde D, Ritchlin CT. Upadacitinib in psoriatic arthritis:56-week results from SELECT-PsA 2. Ann Rheum Dis. 2021;80:312-20.

66.McInnes IB, Kato K, Magrey M. Efficacy and safety of upadacitinib in psoriatic arthritis:results from SELECT-PsA 1. Arthritis Rheumatol. 2021;73:604-16.

67.Gottlieb AB, Merola JF, Papp K. Safety of JAK inhibitors across immune-mediated inflammatory diseases:dermatology perspective. J Eur Acad Dermatol Venereol. 2022;36:1461-72.

68.Rosmarin D, Passeron T, Pandya AG. Ruxolitinib cream in vitiligo:efficacy and safety update. Br J Dermatol. 2023;188:123-32.

69.Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE. Current and emerging treatments for vitiligo. J Am Acad Dermatol. 2017;77:17-29.

70.Harris JE. Vitiligo and JAK inhibitors:a transformative therapeutic paradigm. J Invest Dermatol. 2022;142:1729-31.

71.Craiglow BG, King BA. Kill or cure:JAK inhibitors for alopecia areata. Br J Dermatol. 2021;185:1131-2.

72.King B, Ko J, Ohyama M. Deuruxolitinib for alopecia areata:phase 3 long-term safety and efficacy. J Am Acad Dermatol. 2024;90:789-97.

73.Jabbari A, Nguyen N, Cerise J. Ritlecitinib in alopecia areata:2-year extension results. J Invest Dermatol. 2024;144:112-20.

74.Shapiro J, Tosti A, Rossi A. Emerging treatments for alopecia areata. J Am Acad Dermatol. 2022;86:157-66.

75.Crispin MK, Ko J, Wambier CG. JAK inhibitors in alopecia:mechanisms and clinical translation. Nat Rev Dermatol. 2023;5:222-34.

76.Nogueira M, Torres T. Janus kinase inhibitors for the treatment of vitiligo, alopecia areata, and atopic dermatitis:a review. Dermatol Ther. 2020;33:14110.

77.Campanati A, Ganzetti G, Giuliodori K. JAK/STAT pathway in psoriasis and psoriatic arthritis:therapeutic perspectives. Autoimmun Rev. 2021;20:102736.

78.Sbidian E, Chaimani A, Garcia-Doval I. Systemic pharmacological treatments for chronic plaque psoriasis:a network meta-analysis. Cochrane Database Syst Rev. 2021;1:CD011535.

79.Egeberg A, Andersen YM, Halling-Overgaard AS. Systemic safety of JAK inhibitors in dermatology:real-world registry data. J Eur Acad Dermatol Venereol. 2022;36:1889-97.

80.Guttman-Yassky E, Krueger JG. Janus kinase inhibitors for immune-mediated skin diseases. J Allergy Clin Immunol. 2018;142:1113-26.

81.Almutawa F, Pastar I, Davis SC, Kirsner RS. Role of JAK-STAT signaling in wound healing and chronic wounds. J Invest Dermatol. 2020;140:1277-85.

82.Taveira M, Torres T. Safety of Janus kinase inhibitors in dermatology:practical recommendations. Drugs R D. 2022;22:211-23.

83.Araki T, Shoda H, Nakajima A. Safety of tofacitinib in rheumatoid arthritis and lessons for dermatology. Mod Rheumatol. 2022;32:211-20.

84.Smolen JS, Genovese MC, Takeuchi T, Hyslop DL, Macias WL, Rooney T, et al. Safety profile of baricitinib in immune-mediated diseases:integrated analysis. Ann Rheum Dis. 2020;79:60-70.

85.Dowty ME, Lin J, Ryder TF. The pharmacokinetics, metabolism, and clearance mechanisms of baricitinib, a selective JAK1/JAK2 inhibitor. Drug Metab Dispos. 2014;42:1413-21.

86.Choy EH. Clinical safety of JAK inhibitors:a rheumatology perspective. Rheumatology (Oxford). 2019;58:43-52.

87.Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatology. Nat Rev Rheumatol. 2017;13:234-43.

88.Curtis JR, Lee EB, Kaplan IV. Risk of venous thromboembolism with Janus kinase inhibitors:current evidence and clinical guidance. Ann Rheum Dis. 2023;82:451-8.