Formulations available

Upadacitinib is available as oral tablets in 15 mg, 30 mg, and 45 mg strengths for adult/adolescent use. Pediatric-specific formulations are oral solutions with 1 mg/mL strength. In India, 15 mg is the only strength available at present for dermatological use.

Pregnancy and lactation

Upadacitinib is contraindicated during pregnancy owing to potential teratogenic risk (Category D); women of reproductive potential should employ effective contraception throughout therapy and for at least 4 weeks following the final dose. Breastfeeding is generally not recommended during treatment due to limited safety data and potential risk to the infant. Pregnancy status should be checked at baseline and every month where indicated.^[1,6]

Special populations and polypharmacy

The lowest effective dose should be used in elderly patients and those with cardiovascular or thrombotic risk factors, and the ongoing benefit-to-risk ratio should be periodically reevaluated. Clinicians should check concurrent medications (e.g., CYP3A4 inhibitors and inducers) for possible interactions. According to approved prescribing information and local regulatory guidelines, dose modifications or avoidance may be necessary in cases of severe hepatic or renal impairment.^[1,2,6]

Serious adverse events requiring urgent interruption/cessation

In cases of suspected serious infection/sepsis, disseminated herpes zoster, clinically significant cytopenias, severe hepatitis/transaminitis, suspected thrombosis (deep vein thrombosis (DVT)/pulmonary embolism (PE)/arterial event), or symptoms suggestive of myocardial infarction or stroke, upadacitinib should be immediately stopped and the patient assessed.^[1,6]

AD

AD is a chronic, recurrent inflammatory skin condition caused by a dysregulated immune response that includes dysfunction of the epidermal barrier and Th2, Th22, Th1, and Th17 cytokine activity. Important mediators, including Interleukin (IL)-4, IL-13, IL-31, IL-22, and IFN-γ, communicate through the JAK-STAT pathways, specifically JAK1 [Figure 3].^[8] A selective JAK1 inhibitor, upadacitinib, inhibits signaling downstream of several cytokines linked to the pathophysiology of AD. In doing so, it suppresses IL-31-induced pruritus, lowers IL-4/IL-13-driven Th2 inflammation, and modifies Th1/Th17 cytokines that maintain chronic lesions. Rapid itching suppression, decreased inflammation, and enhanced skin-barrier repair are the outcomes of the ensuing immunomodulation.^[9]

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Figure 3:

Key Janus Kinase 1 (JAK1)–signal transducer and activator of transcription (STAT) signaling pathways modulated by upadacitinib in atopic dermatitis. This schematic illustrates cytokine-driven JAK– STAT pathways central to inflammation, pruritus, and barrier dysfunction in atopic dermatitis and their modulation by upadacitinib, a selective JAK1 inhibitor. Upadacitinib inhibits JAK1-dependent signaling downstream of interleukin (IL)-4 and IL-13, reducing type 2 inflammation; blocks TSLP- and IL-31– mediated pathways involved in neuronal activation and itch; and attenuates IL-22–driven epidermal hyperplasia and barrier impairment. Collectively, the figure highlights the central role of JAK1 across key pathogenic axes in atopic dermatitis and the broad therapeutic impact of its selective inhibition. Key: IL: Interleukin, JAK: Janus kinase,TSLP: Thymic stromal lymphopoietin,TYK: Tyrosine kinase.

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Current clinical evidence

Multiple Phase 3 RCTs and long-term extension studies have consistently demonstrated the efficacy and durability of upadacitinib in moderate-to-severe AD, with rapid improvement in skin clearance, itch, sleep, and quality of life maintained through at least 1 year. Head-to-head and confirmatory trials further show that upadacitinib provides faster and greater clinical responses than dupilumab across body regions, including in adult and adolescent populations [Table 1].^[9-17]

Future scope

Important knowledge gaps remain in the role and use of upadacitinib in AD. Longer-term real-world data beyond current trial durations are needed to better define safety, as well as to refine long-term risk-benefit assessment. Comparative and combination studies with newer biologics will be crucial to guide management protocols, patient selection, and cost-effectiveness, especially in resource-limited settings. Emerging research into biomarker-based stratification and extension of studies into younger pediatric populations and combination regimens may further enable individualized therapy and improve the durability of response.

HS

HS is a chronic inflammatory, relapsing dermatosis characterized by follicular occlusion, draining sinuses, and recurrent abscesses. There is a dysregulation of the innate and adaptive immune system with overexpression of TNF-α, IL-1β, IL-6, IL-17, IL-23, and IFN-γ. These cytokines promote T-cell activation, neutrophil chemotaxis, and keratinocyte hyperproliferation; many of these processes are signaled by JAK1-dependent STAT pathways.

Upadacitinib’s selective JAK1 inhibition affects several inflammatory pathways that are involved in the pathophysiology of HS.^[18] Upadacitinib limits the recruitment and infiltration of activated T cells into lesional skin by inhibiting the IFN-γ/JAK1/STAT1 axis, which in turn lowers the expression of chemokines such as CXCL9 and CXCL10. A key factor in maintaining chronic inflammation in HS is Th17 differentiation and IL-17 production, which are both attenuated by inhibition of the IL-6 and IL-23/JAK1/STAT3 signaling pathway. Furthermore, keratinocyte proliferation and tissue remodeling are normalized through the modulation of the IL-22/JAK1/STAT3 pathway, which aids in the resolution of inflammatory nodules and enhances epithelial repair.

Upadacitinib therapy rapidly decreases IFN-γ-associated and B-cell-linked chemokines in clinical responders, according to translational biomarker research, indicating a mechanistic role for JAK1 blockade in reducing inflammation linked to HS.^[19]

Current clinical evidence

Upadacitinib 30 mg once daily was compared to a placebo in the STEP-UP HS phase 2 randomized, double-blind trial for moderate-to-severe HS.^[20]

Patients with refractory HS who are not responsive to TNF-α or IL-17 blockade have shown significant clinical improvement, according to numerous case reports, case series, and small observational cohorts. A retrospective cohort documented early real-world efficacy and tolerability.^[21] Quick remission was reported in a case report, even after biologic failure.^[22] In severe cases, a synergistic improvement was achieved by combining upadacitinib with either secukinumab or adalimumab [Table 2].^[23-25]

Current clinical evidence

The current body of evidence supporting upadacitinib in psoriasis mainly includes case reports, small series, preclinical research, and data from RCTs in PsA that included cutaneous outcomes as secondary endpoints. No specific large-scale randomized trial has been published for psoriasis alone, although there are strong RCTs for PsA (select- PsA 1 and 2) that showed notable improvements in both joint and skin manifestations.^[27] As a result, small observational studies and actual clinical experience account for the majority of the psoriasis-specific data currently available.^[28-35]

The ability of upadacitinib to modulate shared inflammatory pathways involving IL-4/IL-13, IL-23, and IFN-γ signaling is further demonstrated by cases where psoriasis and AD coexist, and both conditions improved simultaneously on the medication [Table 3].^[36]

The phenotypic switch phenomenon, in which patients receiving upadacitinib for AD developed psoriasiform lesions while undergoing treatment, is a noteworthy finding in the literature.^[37] This highlights the intricate immunological interactions between Th2- and Th17-skewed pathways, indicating that in susceptible individuals, selective JAK1 inhibition may occasionally reveal or change underlying immune predispositions toward a psoriatic phenotype. On the other hand, other reports show that AD and psoriasis can be controlled simultaneously or alternately in the same patient, which reflects the drug’s complex effects on overlapping cytokine networks.

However, it should be noted that specific randomized trials for psoriasis are still needed to determine its effectiveness, durability, and relative role among the available systemic options. Upadacitinib can produce significant clinical improvement across a variety of psoriatic variants in real-world settings.

Current clinical evidence

Oral upadacitinib (6, 11, and 22 mg once daily) was compared to a placebo in adults with extensive non-segmental vitiligo in a multicenter, double-blind, dose-ranging phase 2 RCTs (n = 185).^[40] Clinical improvement was noted in a case of vitiligo treated with a combination of upadacitinib and 308nm excimer laser.^[41]

Combination therapy of upadacitinib and 308 excimer laser was found superior to other monotherapies in a comparative study.^[42] Upadacitinib along with NB - UVB showed notable repigmentation in refractory vitiligo patients.^[43] Significant repigmentation was documented with upadacitinib in a case of paediatric vitiligo.^[44] In a case of coexistent vitiligo and atopic dermatitis, upadacitinib showed complete remission of both AD and vitiligo,^[45] whereas in an another case, AD improved but there was worsening of vitiligo.^[46] Upadacitinib at a dose of 15 mg/day showed repigmentation in a case series.^[47]

In a comparative case series, upadacitinib demonstrated more favourable repigmentation in steroid resistant vitiligo as compared to tofacitinib and baricitinib.^[48]

In another case series, upadacitinib at a dose of 30mg/day showed clinical improvement.^[49] A paediatric case report demonstrated improvement in coexistent vitiligo and alopecia areata.^[50] An another case series showed significant repigmentation and tolerability with upadacitinib in recalcitrant vitiligo.^[51]

In comparison to placebo, the 11 and 22 mg doses resulted in statistically significant improvements in facial vitiligo area scoring index (F-VASI) and total VASI (T-VASI) at Week 24 (LS-mean differences for F-VASI: −21.3 for 11 mg and −19.6 for 22 mg; T-VASI improvements were also significant), and repigmentation persisted through Week 52. To date, these findings offer the most compelling randomized evidence in favor of upadacitinib in vitiligo [Table 4].

Single-patient case reports and small case series from various centers around the world make up the majority of published real-world data. Upadacitinib 15 mg once daily was administered to the majority of patients; in some cases, it was also combined with topical JAK inhibitors or Narrowband Ultraviolet B/308-nm excimer. Early and more noticeable repigmentation is seen at the facial and truncal sites; numerous reports note noticeable repigmentation by 8-16 weeks and ongoing improvement through 24-52 weeks.

LP

LP is a chronic inflammatory dermatosis involving T-cell-mediated destruction of basal keratinocytes. IFN-γ and Th1/Th17 cytokines trigger autoreactive CD8⁺ cytotoxic T cells, which are the main mediators of the condition. Through the JAK1/JAK3-STAT1/STAT3 pathways, these cytokines stimulate keratinocytes, leading to overexpression of CXCL9, CXCL10, and CXCL11, which draws more CD8⁺ cells to the skin and mucosa of lesions.^[52] In addition, IL-15/JAK1/STAT5 signaling promotes resident memory T-cell persistence, which adds to the chronicity and recurrence of the disease. By blocking IFN-γ and IL-15-driven signaling, upadacitinib lowers keratinocyte apoptosis, cytotoxic T-cell recruitment, and downstream chemokine release. It is especially helpful for erosive, mucosal, nail, or hypertrophic LP variants that are resistant to traditional treatments because of its mechanistic targeting.

Current clinical evidence

Upadacitinib in LP has not been the subject of any published RCTs as of late 2025. Nonetheless, a growing amount of empirical evidence, such as case reports and small case series, shows clinical efficacy in erosive, cutaneous, oral, nail, and esophageal variants [Table 4].

Early mechanistic support was highlighted in the earliest reports that described the resolution of erosive oral and esophageal LP.^[ 52,53] Responses in hypertrophic and generalized cutaneous LP that were not responsive to acitretin, cyclosporine, or steroids were confirmed by later series.^[54,55]

With upadacitinib 15-30 mg daily, oral and nail LP forms have also demonstrated long-lasting improvement, frequently accompanied by notable declines in severity indices such as the nail LP severity index.^[56,57]

Clinical improvement was reported within 4-12 weeks, and adverse events were mild. No new safety concerns were observed beyond the known JAK1 inhibitor profile. Currently, upadacitinib in LP is not being specifically evaluated in any registered Phase 2 or Phase 3 RCTs. The objectives of future studies include relapse prevention, dose optimization, and comparative effectiveness with other JAK inhibitors [Table 5].

AA

Autoreactive CD8⁺ cytotoxic T cells specifically destroy anagen hair follicles in AA. These lymphocytes interfere with hair-follicle immune privilege by secreting proinflammatory cytokines such as IFN-γ. In follicular keratinocytes, IFN-γ signals through the JAK1/JAK2 → STAT1 pathway, triggering the expression of the chemokines CXCL9 and CXCL10, which attract more cytotoxic T cells and maintain follicular inflammation.^[57] IL-15 contributes to the persistence of disease via JAK1/JAK3 → STAT5 signaling, which promotes the survival of pathogenic tissue-resident memory T cells. Upadacitinib breaks the inflammatory loop and restores an environment that promotes hair regrowth by attenuating both IL-15-dependent T-cell survival and IFN-γ-driven chemokine production.^[58] This mechanism reflects results from clinical data and translational models that demonstrate reversal of IFN-γ signatures after JAK inhibition.

Current clinical evidence

According to real-world data, upadacitinib significantly increases hair growth in AA patients of all ages, including those who are resistant to other JAK inhibitors.^[59-62] The majority of reports showed clinically significant hair growth in 3-6 months, frequently with eyelash and eyebrow regrowth as well. Early response onset (within 1-2 months) was observed in several adolescent case series. Interestingly, some patients who had previously failed conventional therapies showed improvement with upadacitinib. Although there are no RCTs, the consistency of positive clinical outcomes across several centers offers compelling empirical support for its therapeutic role [Table 6].

Limitations

The review has several limitations. The quality of the evidence varies significantly among dermatologic indications; AD is the only indication with strong randomized data, while the majority of other indications rely on small cohorts, case series, or case reports, which may have publication bias and inconsistent outcome measures. Long-term safety results in dermatology might not be entirely extrapolated from other immune-mediated disease cohorts. For the majority of conditions, optimal duration, discontinuation strategies, and relapse rates are still unknown, and there are few head-to-head comparisons with biologics. For the majority of conditions, optimal duration, discontinuation strategies, and relapse rates are still unknown, and there are few head-to-head comparisons with biologics [Table 7].