tofacitinib and Vitiligo

With recent advancements in the understanding of vitiligo pathogenesis, Janus kinase (JAK) inhibitors have emerged as a promising new treatment modality, but their effects remain incompletely elucidated. Tofacitinib, an oral JAK 1/3 inhibitor approved for the treatment of rheumatoid arthritis, has previously been shown to induce significant re-pigmentation in vitiligo. However, as with other novel targeted therapies, cutaneous adverse effects have been observed. We report a 36-year-old woman with a history of rheumatoid arthritis, refractory to multiple pharmacotherapies, who was initiated on tofacitinib and subsequently developed progressive depigmented patches consistent with new-onset vitiligo. Although definitive causation cannot be established in this case without additional studies, it is important to note that many targeted therapies have the potential to induce paradoxical effects, that is, the occurrence or exacerbation of pathologic conditions that have been shown to respond to these medications. Paradoxical findings with other targeted therapies include the occurrence of melanoma during treatment with BRAF inhibitors, keratoacanthomas with PD-1 inhibitors, vitiligo and psoriasis with TNF-alpha inhibitors, and hidradenitis suppurativa with various biologic agents. Although JAK inhibitors hold therapeutic promise in the treatment of inflammatory skin disorders, further research is warranted to more fully comprehend their effects.

Topics: Adult; Arthritis, Rheumatoid; Female; Hidradenitis Suppurativa; Humans; Janus Kinase Inhibitors; Keratoacanthoma; Melanoma; Piperidines; Programmed Cell Death 1 Receptor; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Psoriasis; Pyrimidines; Pyrroles; Tumor Necrosis Factor-alpha; Vitiligo

Medical treatments alone, or in combination with phototherapy, are key approaches for treating nonsegmental vitiligo and, to a lesser extent, segmental vitiligo. The treatments are useful for halting disease progression and have been proven effective for inducing repigmentation and decreasing risk of relapses. Although the treatments have side effects and limitations, vitiligo often induces a marked decrease in quality of life and in most cases the risk:benefit ratio is in favor of an active approach. Systemic and topical agents targeting the pathways involved in loss of melanocytes and in differentiation of melanocyte stem cells should provide more effective approaches in the near future.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; alpha-MSH; Anti-Bacterial Agents; Calcineurin Inhibitors; Dinoprostone; Humans; Immunosuppressive Agents; Low-Level Light Therapy; Methotrexate; Minocycline; Oxytocics; Phototherapy; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Ultraviolet Therapy; Vitamin D; Vitiligo

Systemic drug treatment of vitiligo is currently limited to predominantly adjuvant measures for increasing the effectiveness of UV light therapy. We here present new approaches for the systemic treatment of vitiligo currently under clinical investigation. These include the α‑MSH-analogue afamelatonide and oral immunosuppressants such as the Janus kinase (JAK) inhibitors which target interferon-α-dependent autotoxic inflammatory reactions. In 2015 the first publications on the successful systemic use of Janus kinase (JAK) inhibitors in vitiligo appeared. The effectiveness was experimentally supported by animal models of vitiligo and by the characterization of new biomarkers in the serum of vitiligo patients. This may significantly expand the range of treatment options for vitiligo. Topical antiinflammatory and UV therapies are still the main components of vitiligo treatment, often in combination. The main outcome parameters include the extent and duration of repigmentation, cessation of spreading, avoidance of side effects and improvement in the quality of life of patients.

Topics: alpha-MSH; Animals; Biomarkers; Combined Modality Therapy; Disease Models, Animal; Humans; Immunosuppressive Agents; Interferon-alpha; Janus Kinases; Nitriles; Piperidines; Pyrazoles; Pyrimidines; Pyrroles; Ultraviolet Therapy; Vitiligo

Janus kinase family (JAKs) has recently attracted the attention of many researchers, and several JAK inhibitor drugs have been developed targeting different members of the JAK family. Tofacitinib and ruxolitinib are US FDA approved drugs in this family for rheumatoid arthritis and myeloproliferative diseases, respectively. Dysregulation of JAK/STAT pathway is also involved in many skin diseases, specifically inflammatory disorders. The JAK/STAT signaling pathway and its involvement in skin diseases are overviewed in this study. We also review clinical studies of JAK inhibitors in field of dermatology, including psoriasis, atopic dermatitis, alopecia areata and vitiligo. Although the available evidence shows promising results, it is still too early to draw a firm conclusion about the place of these drugs in dermatological treatment.

Topics: Alopecia Areata; Azetidines; Dermatitis, Atopic; Humans; Janus Kinase Inhibitors; Janus Kinases; Nitriles; Piperidines; Psoriasis; Purines; Pyrazoles; Pyrimidines; Pyrroles; Skin Diseases; Sulfonamides; Vitiligo

Tofacitinib (formerly known as CP-690,550, CP690550, tasocitinib), a novel selective immunosuppressant, is a small molecule classified as Janus kinase inhibitor. The aim of this review article is to present updated data summary on the tofacitinib in the field of dermatology.. We undertook a structured search of bibliographic databases for peer-reviewed scientific articles, including review articles, original research articles as well as case report articles based on inclusion/exclusion criteria. Technical reports on tofacitinib from U.S. Food and Drug Administration and European Medical Agency were also included.. Forty-three papers were included in this review. We report current data on tofacitinib chemical properties, pharmacology, non-clinical toxicity, as well as efficacy and safety in potential new indications in dermatology: psoriasis, alopecia areata, vitiligo, atopic dermatitis and nail dystrophy associated with alopecia areata.. JAK/STAT pathway has an important role in the pathogenesis of psoriasis, alopecia areata, atopic dermatitis, and vitiligo. Despite encouraging efficacy, due to concerns about the overall safety profile of tofacitinib, additional studies will have to determine the adequate risk-to-benefit ratio.

Topics: Administration, Oral; Alopecia Areata; Dermatitis, Atopic; Humans; Janus Kinases; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Pyrroles; Signal Transduction; Skin Diseases; Vitiligo

New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase-signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

Topics: Alopecia Areata; Anti-Inflammatory Agents; Azetidines; Clinical Trials as Topic; Dermatitis, Atopic; Dermatologic Agents; Humans; Janus Kinases; Molecular Targeted Therapy; Nitriles; Piperidines; Protein Kinase Inhibitors; Psoriasis; Purines; Pyrazoles; Pyrimidines; Pyrroles; Signal Transduction; Skin Diseases; Sulfonamides; Vitiligo

Topics: Humans; Hypopigmentation; Piperidines; Pyrimidines; Vitiligo

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.

Topics: alpha-MSH; Dextrans; Humans; Hydrogels; Melanocytes; Vitiligo

Topics: Combined Modality Therapy; Humans; Hypopigmentation; Phototherapy; Piperidines; Pyrimidines; Treatment Outcome; Ultraviolet Therapy; Vitiligo

Combining low-dose tofacitinib with 308-nm excimer may be an effective treatment for patients with nonsegmental vitiligo who were refractory to conventional therapies.

Topics: Humans; Low-Level Light Therapy; Piperidines; Pyrimidines; Treatment Outcome; Vitiligo

Janus Kinase inhibitors have been shown to be effective in the treatment of various dermatoses such as alopecia areata, psoriasis, vitiligo and atopic dermatitis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is a common junction for the signaling of several dermatologically significant cytokines and the inhibition of this pathway by JAK inhibitors may be broadly useful in the treatment of various other dermatological disorders. A case series is presented of twelve patients (M:6, F:6) with a mean age 47.1 years, presenting with various eczematous dermatoses (histopathology showing spongiotic dermatitis) who had failed to respond to conventional therapy. These patients were prescribed tofacitinib. All 12 patients improved and 10 patients had improvement to clear or almost clear (physician global assessment score 0/1) after 1 month of therapy. No hematological or biochemical abnormalities were noted during the treatment period. Infections were the most common adverse events observed. Conventional treatment options like systemic steroids and steroid sparing agents are the cornerstone in the treatment of chronic eczematous disorders, however, in patients who do not respond to conventional agents, tofacitinib may represent a viable treatment option.

Topics: Eczema; Humans; Janus Kinase Inhibitors; Middle Aged; Pyrimidines; Vitiligo

Vitiligo is a chronic treatment-resistant autoimmune disorder characterized by circumscribed depigmented maculae. This study was conducted to evaluate the efficacy and safety of tofacitinib combined with narrowband ultraviolet B (NB-UVB) phototherapy for refractory nonsegmental vitiligo. Fifteen patients with nonsegmental vitiligo resistant to conventional therapies were administered oral tofacitinib at 5 mg twice daily plus topical halometasone cream, tacrolimus 0.1% ointment, or pimecrolimus cream twice daily and NB-UVB three times per week for 16 weeks. The control group comprised 19 patients with nonsegmental vitiligo treated with topical drugs plus NB-UVB same as the combination group. Treatment efficacy was measured by the percentage of repigmentation of vitiligo lesions at 4th, 8th, 12th, and 16th week after beginning treatment. From 8th week, the repigmentation level was significantly higher in the combination group than in the controls. From fourth week, the response rate was significantly higher in the combination group than in the controls. Only one patient in the combination group reported mild pain in the hand and foot joints, but the pain subsided with cessation of therapy. No other severe adverse effects occurred. So, tofacitinib in combination with NB-UVB phototherapy may be an effective and safe alternative modality for refractory vitiligo.

Topics: Chronic Disease; Combined Modality Therapy; Emollients; Humans; Pain; Phototherapy; Prospective Studies; Treatment Outcome; Ultraviolet Therapy; Vitiligo

Vitiligo is an autoimmune disease where its current treatment strategies are lengthy in course and do not guarantee complete cure. Tofacitinib citrate (JAK inhibitor) is a potential cure of vitiligo through halting JAK-STAT pathway preventing the destruction of melanocytes. The dermato-pharmacokinetics of the prepared transethosomes (Et) and the hybridized ethosomes/nanostructured lipid carriers (Eth/NLC), namely formulations; M.E-Cr and M.E-S.M, were evaluated. In addition, in vivo studies on C57/BL6 vitiligo mouse model were conducted to confirm effectiveness of Tofacitinib citrate delivery. The results unveiled that the transethosomes (359.46 ± 11.82 nm) were suitable for dermal delivery while M.E-Cr (179.64 ± 11.16 nm), a hybrid Eth/NLC formulation, was mostly suitable for transdermal delivery. Nevertheless, another hybrid formulation, M.E-S.M (253.60 ± 14.64 nm), was apt for both dermal and transdermal delivery. The histopathology confirmed re-pigmentation of mice skin where formulations Et and M.E-S.M showed severe pigmentation compared to the control healthy and induced mice. On the other hand, M.E-Cr showed mild pigmentation. Immunohistochemical assay was performed to evaluate infiltration of CD 8

Topics: Animals; Drug Carriers; Janus Kinases; Lipids; Mice; Signal Transduction; Skin; STAT Transcription Factors; Vitiligo

In the last several years, oral tofacitinib has become an increasingly utilized off-label treatment option for immune-mediated skin conditions such as alopecia areata (AA), vitiligo, plaque psoriasis, and atopic dermatitis. Few case reports exist of patients with concomitant AA and vitiligo treated with tofacitinib.. Photographs of the patient's affected disease areas were obtained at initiation of tofacitinib 5 mg twice daily (BID) and subsequent return visits over two years of treatment. A PubMed search for case reports and other relevant literature was performed using the keywords: alopecia areata, vitiligo, and tofacitinib.. Two case reports in the literature describe patients with concomitant AA and vitiligo who were treated with tofacitinib. Both cases use adjuvant therapy or continued therapy, in addition to oral tofacitinib. Our patient was treated with low-dose tofacitinib monotherapy and had marked improvement in her AA and vitiligo, with moderate re-pigmentation of her hands and regrowth of the scalp and eyebrows within several months of treatment. Treatment effects continued to improve over two years without noted adverse effects.. Tofacitinib 5 mg BID monotherapy was an efficacious and well-tolerated treatment option for a patient with refractory alopecia areata and vitiligo. J Drugs Dermatol. 2022;21(12):1366-1368. doi:10.36849/JDD.6826.

Topics: Alopecia Areata; Female; Humans; Pyrroles; Vitiligo

Topics: Combined Modality Therapy; Humans; Pilot Projects; Piperidines; Pyrimidines; Treatment Outcome; Ultraviolet Therapy; Vitiligo

Topics: Humans; Pilot Projects; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Treatment Outcome; Vitiligo

Segmental vitiligo often presents in childhood and tends to be more recalcitrant to therapy than generalized vitiligo. Recently, Janus kinase inhibitors have emerged as a promising treatment option, with some reports suggesting that concomitant ultraviolet light exposure may enhance therapeutic response. Here, we present a child with segmental vitiligo who responded rapidly and completely to treatment with tofacitinib cream plus phototherapy.

Topics: Child; Humans; Phototherapy; Piperidines; Pyrimidines; Pyrroles; Treatment Outcome; Ultraviolet Therapy; Vitiligo

Hypopigmentation and depigmentation of the skin can be due to multiple causes and has a broad differential diagnosis. The most common cause of depigmentation worldwide is vitiligo. This disorder affects 1-2% of the world’s population and is seen in all races. Vitiligo is an autoimmune disorder in which the predominant cause is an attack by CD8+ cytotoxic T cells on melanocytes in the epidermis. This condition can have a significant negative impact on the quality of life of affected individuals. Treatment options currently include psychological counseling, topical therapy, systemic therapy, phototherapy, surgical therapy, and depigmentation. In patients with stable, refractory disease, successful repigmentation has been achieved using mini-punch grafting, blister grafting, and non-cultured epidermal suspension (NCES) grafting. Emerging therapies include the Janus kinase (JAK) inhibitors ruxolitinib and tofacitinib. Further studies exploring the pathogenesis of vitiligo are warranted in order to optimize treatment for affected patients.\ \ J Drugs Dermatol. 2019;18(3 Suppl):s115-116.

Topics: Administration, Cutaneous; Administration, Oral; Autoimmune Diseases; CD8-Positive T-Lymphocytes; Counseling; Dermatologic Agents; Diagnosis, Differential; Epidermis; Humans; Janus Kinases; Melanocytes; Mycosis Fungoides; Nitriles; Phototherapy; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Pyrroles; Quality of Life; Skin Pigmentation; Tinea Versicolor; Vitiligo

Topics: Administration, Oral; Animals; Butanols; Disease Models, Animal; Humans; Janus Kinase Inhibitors; Mice; Mice, Hairless; Mice, Transgenic; Piperidines; Pyrimidines; Pyrroles; Skin Lightening Preparations; Skin Pigmentation; Treatment Failure; Vitiligo

Topics: Administration, Cutaneous; Adult; Combined Modality Therapy; Facial Dermatoses; Female; Humans; Male; Pilot Projects; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Severity of Illness Index; Skin Cream; Ultraviolet Therapy; Vitiligo

Topics: Adult; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Skin Pigmentation; Ultraviolet Therapy; Vitiligo

Vitiligo is an autoimmune disease in which cutaneous depigmentation occurs. Existing therapies are often inadequate. Prior reports have shown benefit of the Janus kinase (JAK) inhibitors.. To evaluate the efficacy of the JAK 1/3 inhibitor tofacitinib in the treatment of vitiligo.. This is a retrospective case series of 10 consecutive patients with vitiligo treated with tofacitinib. Severity of disease was assessed by body surface area of depigmentation.. Ten consecutive patients were treated with tofacitinib. Five patients achieved some repigmentation at sites of either sunlight exposure or low-dose narrowband ultraviolet B phototherapy. Suction blister sampling revealed that the autoimmune response was inhibited during treatment in both responding and nonresponding lesions, suggesting that light rather than immunosuppression was primarily required for melanocyte regeneration.. Limitations include the small size of the study population, retrospective nature of the study, and lack of a control group.. Treatment of vitiligo with JAK inhibitors appears to require light exposure. In contrast to treatment with phototherapy alone, repigmentation during treatment with JAK inhibitors may require only low-level light. Maintenance of repigmentation may be achieved with JAK inhibitor monotherapy. These results support a model wherein JAK inhibitors suppress T cell mediators of vitiligo and light exposure is necessary for stimulation of melanocyte regeneration.

Topics: Adult; Aged; Autoimmunity; Chemokine CXCL10; Chemokine CXCL9; Combined Modality Therapy; Female; Humans; Janus Kinase 1; Janus Kinase 3; Male; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Retrospective Studies; Severity of Illness Index; Skin Pigmentation; Ultraviolet Therapy; Vitiligo

Topics: Adult; Alopecia Areata; Dermatitis, Atopic; Humans; Janus Kinase Inhibitors; Male; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Th2 Cells; Treatment Outcome; Vitiligo

Vitiligo is a common condition that is often emotionally devastating for patients. At present, no reliably effective treatments are available.. Recent advances in the understanding of the pathogenesis of vitiligo suggest that Janus kinase inhibitors may be a therapeutic option. We report a case of generalized vitiligo for which treatment with tofacitinib citrate, an oral Janus kinase 1/3 inhibitor, resulted in significant repigmentation.. The results suggest that tofacitinib and other Janus kinase inhibitors may be effective in the treatment of vitiligo. Additional studies will be needed to confirm their efficacy and to explore their safety.

Topics: Administration, Oral; Female; Humans; Janus Kinase 1; Janus Kinase 3; Middle Aged; Piperidines; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Skin Pigmentation; Treatment Outcome; Vitiligo