Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

Response to Biologic Therapy in Skin of Colour Participants With Moderate-to-Severe Psoriasis and Atopic Dermatitis: A Systematic Review.

There has been a call to action to enhance representation of non-white individuals in dermatology clinical trials. Investigations in differential response to treatment across populations are limited, particularly in conditions of commonality, impact, distinct presentation, and diagnosis in non-white participants, such as atopic dermatitis and psoriasis. This systematic review summarized and identified if biologic treatment outcomes in moderate-to-severe atopic dermatitis and psoriasis varied in skin of colour (SOC) participants in phase 3 trials. MEDLINE, COCHRANE, and EMBASE databases were used to conduct the search following PROSPERO registration. Following screening of 3209 articles, 11 studies were collected with 1781 SOC participants with a mean age of 40.99 ± 6.3 years (range: 30.6-51.6 years). Male participants accounted for 76.9% (n = 1370/1781) of the sample, and Chinese, Japanese, Taiwanese, and Korean participants accounted for 64.3%, 24.2%, 4.5%, and 3.4% of participants, respectively. Participants with atopic dermatitis were treated with dupilumab (n = 216/388) and participants with psoriasis were treated with adalimumab (n = 313/1393), bimekizumab (n = 62/1393), ixekizumab (n = 13/1393), secukinumab (n = 117/1393), and ustekinumab (n = 289/1393). No significant SOC population-based outcomes were found across treatment groups. However, differences in baseline characteristics or comorbidities were found, suggesting race or ethnic background should be considered when treatment is prescribed in psoriasis or atopic dermatitis. Although no significant SOC participant differential response to treatment were found, large-scale randomized controlled trials investigating comparable treatment outcomes and stratifying results by SOC population in atopic dermatitis and psoriasis are warranted to confirm these findings.

Spesolimab, A Novel Interleukin-36 Inhibitor for Generalized Pustular Psoriasis Flares in Adult Patients.

Generalized pustular psoriasis (GPP) is a rare, immune-mediated inflammatory disease with characteristic cutaneous and systemic manifestations. Mutations in the interleukin-36 receptor antagonist (IL36RN) gene have been implicated in its pathogenesis. Spesolimab is a novel systemic biologic therapy that selectively inhibits interleukin-36. It was recently approved by Health Canada and the US FDA for the treatment of GPP flares in adults. Results from phase 1 and 2 studies have been promising. Herein, we review the efficacy and safety of spesolimab for the treatment of GPP flares, as demonstrated in clinical trials.

Brodalumab-Induced Eczematous Reactions in Psoriasis Patients: Management With Switching to Risankizumab.

Biological treatments targeting IL-17 are highly efficacious with rapid onset of action in psoriasis. Cutaneous adverse events are associated with different biological treatments, including paradoxical psoriasis and eczematous reactions. Brodalumab was previously suggested as an alternative treatment option in psoriasis patients who developed dermatitis or paradoxical psoriasis while on a biologic. Here we report three psoriasis patients who developed brodalumab induced eczematous reaction with complete clearance after switching to risankizumab. Early recognition is crucial for appropriate management. We propose switching patients with psoriasis who develop severe eczematous reaction while on a biologic targeting IL-17 to an IL 23 inhibitor due to efficacy in psoriasis and rarely reported eczematous reaction.

The Use of Janus Kinase Inhibitors for Lichen Planus: An Evidence-Based Review.

BACKGROUND: Lichen Planus (LP) is a dermatological disorder characterized by violaceous papules that affect the cutaneous region, nails, scalp, and mucous membranes. Current molecular and clinical studies point to the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway as a potential effector of LP pathology. OBJECTIVE: This systematic review summarizes the current reported literature outcomes for patients receiving JAK inhibitors to treat LP. METHODS: MEDLINE and Embase were searched on 16 October, 2022, and 15 original articles were included, with 56 LP patients. RESULTS: (mean age: 54.5 years, range: 26-81 years, male: 26.8%). The treatment outcomes were included for the following JAK inhibitors: tofacitinib (n = 30), baricitinib (n = 16), ruxolitinib (n = 12), and upadacitinib (n = 2). Patient outcomes were classified into complete resolution, partial resolution, and no resolution. Patients achieving complete resolution represented 25% (n = 4/16) in the baricitinib group, 10% (n = 3/30) in the tofacitinib group, 16.7% (n = 2/12) in the ruxolitinib group, and 100% (2/2) in the upadacitinib group. Partial resolution patients represented 31.3% (n = 5/16) of baricitinib patients, 60% (n = 18/30) of tofacitinib patients, and 83% (n = 10/12) of ruxolitinib patients. 43.8% (n = 7/16) of baricitinib patients and 10% (n = 9/30) of tofacitinib patients had no resolution of lesions. CONCLUSION: This review also highlights the significance of utilizing a uniform outcome measure for LP, as it aids in reporting more generalizable results, reduces reporting bias, and ultimately lead to improved clinical outcomes for LP patients.

Risankizumab in Adults with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease associated with psoriasis. Its major clinical domains include peripheral and axial arthritis, enthesitis, dactylitis and skin and nail involvement. Approximately 30% of patients with psoriasis develop psoriatic arthritis. The pathophysiology of PsA is complex and involves a dysregulated immune response. In particular, interleukin (IL)-23 is a major regulatory cytokine that has been implicated in PsA, including bone remodeling, enthesitis, synovitis and psoriatic lesions. Risankizumab is a humanized immunoglobulin G1 monoclonal antibody that targets the p19 subunit of IL-23. It has been approved for the treatment of moderate-to-severe plaque psoriasis and, more recently, PsA. The efficacy and safety of risankizumab for the treatment of PsA has been demonstrated in phase 2 and phase 3 clinical trials. Risankizumab showed efficacy in decreasing the number of swollen and tender joints, clearing psoriatic plaque and improving quality of life. Treatment with risankizumab was well-tolerated, with the most common adverse event being upper respiratory tract infection. Overall, the current literature demonstrates that risankizumab is both a safe and effective therapeutic option for the treatment of PsA. Herein, week 24 and 52 results are reviewed.

Tralokinumab for Moderate-to-Severe Atopic Dermatitis in Adults.

Atopic dermatitis (AD) is a common, chronic, recurrent, immune-mediated inflammatory skin disease. Targeted treatment options remain limited. Tralokinumab (Adtralza®) is a promising, new systemic therapy that inhibits interleukin-13. It was recently approved by Health Canada and the US FDA for the treatment of moderate-to-severe AD in adults and may be used alone or with topical corticosteroids. Herein, we review the efficacy and safety of tralokinumab in adults, as demonstrated in clinical trials.

Biologic treatment outcomes in mucous membrane pemphigoid: A systematic review.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune disease that can lead to fibrosis of mucous membranes and functional impairment. Biologic agents should be explored as alternative treatment options to improve outcomes. OBJECTIVE: To conduct a systematic review of biologic treatment outcomes in patients with MMP. METHODS: A MEDLINE and Embase search was conducted on July 23, 2020, to include 63 studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Use of intravenous immunoglobulin (n = 154), rituximab (n = 112), tumor necrosis factor α inhibitors (n = 7), and combination treatments (n = 58) were reported in 331 patients with MMP. Intravenous immunoglobulin led to complete resolution in 61.7% (n = 95/154) of patients within 26.0 months, with a recurrence rate of 22.7% (n = 35/154) and headache as the most common adverse effect (8.4%, n = 13/154). Rituximab led to complete resolution in 70.5% (n = 79/112) of patients within 8.7 months, with a recurrence rate of 35.7% (n = 40/112). The most commonly reported adverse effects were urinary tract infections (4.5%, n = 5/112), leukocytopenia (2.7%, n = 3/112), and death due to severe infections (1.8%, n = 2/112). Tumor necrosis factor α inhibitors led to complete resolution in 71.4% (n = 5/7) of patients within 3.9 months of treatment without reported adverse events. CONCLUSIONS: Randomized clinical trials with long-term follow-up are required to conclude the promising safety and efficacy of biologic agents in patients with MMP.

Management of moderate-to-severe plaque psoriasis with biologics: A treat-to-target position paper.

Treat-to-target (T2T) recommendations for the use of systemic therapies (including biologics) in patients with moderate-to-severe plaque psoriasis have been published by a few groups of experts worldwide. However, there remains considerable variability in the choice of target severity measure and timing of milestones. To develop consensus recommendations for implementing T2T strategies for the management of moderate-to-severe plaque psoriasis using biologics. An expert group of Canadian dermatologists (the Committee) convened to develop a T2T consensus statement. They held a virtual meeting during which a preliminary set of criteria was created. These criteria were then reviewed, modified, and recirculated until unanimous agreement was achieved. The Committee agreed that defining treatment target is multidimensional and should reflect objective severity measures, as well as clinician and patient-reported outcomes. The Committee unanimously proposes a criterion-based system for determining the achievement of treatment target. The proposed T2T approach presented here provides a clinical framework for defining treatment success, measuring progress toward treatment success, recognizing when treatment modifications are warranted, and recommending treatment optimization strategies.

A Systematic Review Characterizing Psoriatic Arthritis Onset and Exacerbation in Patients Receiving Biologic Therapy.

BACKGROUND: While biologic therapies revolutionized treatment of immune-mediated inflammatory diseases (IMIDs), some adverse effects have been noted. This includes the development and exacerbation of PsA in patients on biologic agents, however the outcomes were not extensively explored. OBJECTIVE: To perform a systematic review to characterize the outcomes of PsA onset or exacerbation secondary to biologic use. METHODS: MEDLINE and EMBASE search conducted on March 23, 2021 resulted in 18 studies comprised of 64 patients. RESULTS: Of the 64 patients, 57 (89.1%) experienced new-onset PsA and 7 (10.9%) experienced exacerbation of preexisting PsA following exposure to a biologic; most commonly a TNF-α inhibitor (42.2%, n = 27/64) and IL-12/23 inhibitors (39.1%, n = 25/64). The mean durations of biologic use before PsA onset and exacerbation were 14.8 months and 5.2 months, respectively. Twenty-four patients (44.4%) subsequently switched to an alternate biologic without further reports of PsA-related adverse events. All 64 patients reported a specific treatment for PsA; most commonly discontinuation of the associated biologic agent (32.8%, n = 21/64). Complete resolution of PsA was reported in 35.9% (n = 23/64) of cases, of which 91.3% (n = 21/23) resulted after discontinuation of biologic. CONCLUSION: Although we characterized outcomes of PsA induction and exacerbation secondary to biologic use, large-scale studies are required.

Eruptive Seborrheic Keratoses Are Associated With a Co-Occurring Malignancy in the Majority of Reported Cases: A Systematic Review.

BACKGROUND: Eruptive seborrheic keratoses (ESK) is a benign skin condition that has been associated with malignant and nonmalignant diseases. We conducted a systematic review of reported cases of ESK to identify and summarize associated comorbidities. METHODS: MEDLINE and Embase were searched from database inception (1946) to July 31, 2020 for original articles describing ESK with or without a co-occurring condition. Subject demographics, as well as details of ESK and associated diagnoses were extracted from 76 articles (70 case reports, 3 case series, 3 case control studies) representing 92 patients. RESULTS: In total, 76.1% (n = 70/92) of patients with ESK had a co-occurring malignancy, 4.3% (n = 4/92) presented with a nonmalignant condition, 9.8% (n = 9/92) experienced ESK as an adverse drug reaction, and 9.8% (n = 9/92) did not report any underlying medical condition. ESK preceded a cancer diagnosis in 76.1% (n = 70/92) of patients with a mean latency period of 4.0 months (range: 0.25-9 months). The most common malignancies associated with ESK were cutaneous T-cell lymphoma (n = 10/70, 14.3%) and gastrointestinal adenocarcinoma (n = 9/70, 12.9%). ESK preceded nonmalignant conditions or no disease in 14.1% (n = 13/92) of patients with a mean latency period of 3.1 months (range: 0.75-6 months). Drug-induced ESK occurred in 9.8% (n = 9/92) of patients with a mean latency period of 7.1 weeks after changing medication. CONCLUSION: Although the role of ESK as a paraneoplastic cutaneous marker is debated, healthcare providers should consider screening for underlying malignancy in patients presenting with ESK. Larger studies are needed to confirm its role as a marker for disease.

Review and Practical Guidance on Managing Fungal Infections in Patients With Psoriasis Receiving Anti-IL-17 Therapies.

The IL-17 signalling pathway is a major target in treatment of plaque psoriasis. IL-17 signalling contributes to chronic inflammation and epidermal hyperplasia seen in psoriatic lesions. Blocking the IL-17 signalling cascade is an effective method in treating this disease. However, IL-17 also plays a role in the immunological protection against fungal infections and therefore, patients on IL-17 biologics experience an increased rate of fungal infections, specifically Candida albicans. It is prudent that patients and physicians are aware of this risk and understand how to recognize and manage Candida infections. In this review, we examine the Candida infection rates associated with IL-17 biologics, both in clinical trials and real-world practice. We discuss common presentations associated with various types of candidiasis and propose a recommended management approach to treating these infections.

Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review.

The IL-17 pathway is a potential therapeutic target shown to be implicated in hidradenitis suppurativa (HS), however, it remains unclear whether evidence from mechanistic studies may translate into clinical practice. This systematic review summarizes available treatment outcomes of IL-17 inhibitors in patients with HS. Embase, MEDLINE, PubMed, and clinicaltrials.gov were comprehensively searched on February 26, 2021 to include 16 original studies representing 128 patients with HS (mean age: 36.5 years; age range: 21-47 years; male: 50.0%). Treatment outcomes were reported for the following biologics: secukinumab (n = 105), brodalumab (n = 22), and ixekizumab (n = 1). Patients were classified as responders or non-responders according to achievement of a positive response/improvement based on criteria established for each included study. For secukinumab 57.1% (n = 60/105) of patients were responders in a mean response period of 16.2 weeks and 42.9% (n = 45/105) were non-responders; for brodalumab, 100.0% (n = 22/22) of patients were responders within 4.4 weeks; and the one patient treated with ixekizumab was a responder within 10 weeks. In conclusion, IL-17 inhibitors may serve as an effective therapeutic target in approximately two-thirds of patients with HS and can be considered in those who are refractory to other treatment modalities. We also stress the importance of consistent outcome measures to enhance evidence synthesis, decrease reporting bias, provide potential for future meta-analysis, and ultimately improve clinical outcomes for patients with HS.

Differences in Practice Patterns and Payments for Female and Male Dermatologists: A Canadian Population-Based Study Over 3 Decades.

BACKGROUND: Canada's fee-for-service physician reimbursement system, where a set rate is provided for each service, suggests that a physician sex pay gap should not exist. However, recent evidence has questioned this presumption. OBJECTIVES: To characterize trends in demographics and billing, overall and by sex, for dermatologists compared to other medical and surgical specialty groups in Ontario, Canada. METHODS: Using population-based data, analysis of physician billing and clinical activity from Ontario, Canada, over 27 years (1992-2018) was performed. Multilevel regression models were used to examine unadjusted and adjusted differences in payments between females and males over time, while controlling for age, distinct patients seen, patient visits, and full-time equivalent. RESULTS: A total of 22 389 physicians were included in the analyses, including 381 dermatologists. The proportion of female dermatologists increased from 32% in 1992 to 46% in 2018. Dermatologists' median Ontario Health Insurance Plan (OHIP) payments were $415 340 (IQR: 285 630-566 580) in 1992 compared to $296 750 (IQR: 164 480-493 180) in 2018. Male dermatologists' OHIP payments were 20% more than their female counterparts across the entire study period. After adjusting for practice volumes, there was no significant pay gap amongst female and male dermatologists (P = .42); however, the sex pay gap remained significant for the other specialty groups (P < .001). From 1992 to 2018, dermatologists on average saw 19% fewer distinct patients per year and 15% fewer visits per patient. CONCLUSIONS: The overall sex pay gap within medical dermatology can be attributed to differences in practice patterns, whereas the sex pay gap remained significant in the other specialty groups.

Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis and Corticosteroid-Responsive Dermatoses.

A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes.

Onset of Pyoderma Gangrenosum in Patients on Biologic Therapies: A Systematic Review.

OBJECTIVE: To summarize clinical outcomes of paradoxical pyoderma gangrenosum (PG) onset in patients on biologic therapy. METHODS: The authors conducted MEDLINE and EMBASE searches using PRISMA guidelines to include 57 patients (23 reports). RESULTS: Of the included patients, 71.9% (n = 41/57) noted PG onset after initiating rituximab, 21.1% (n = 12/57) noted tumor necrosis factor α (TNF-α) inhibitors, 5.3% (n = 3/57) reported interleukin 17A inhibitors, and 1.8% (n = 1/57) reported cytotoxic T-lymphocyte-associated protein 4 antibodies. The majority of patients (94.3%) discontinued biologic use. The most common medications used to resolve rituximab-associated PG were intravenous immunoglobulins, oral corticosteroids, and antibiotics, with an average resolution time of 3.3 months. Complete resolution of PG in TNF-α-associated cases occurred within an average of 2.2 months after switching to another TNF-α inhibitor (n = 1), an interleukin 12/23 inhibitor (n = 2), or treatment with systemic corticosteroids and cyclosporine (n = 3), systemic corticosteroids alone (n = 1), or cyclosporine alone (n = 1). CONCLUSIONS: Further investigations are warranted to determine whether PG onset is associated with underlying comorbidities, the use of biologic agents, or a synergistic effect. Nevertheless, PG may develop in patients on rituximab or TNF-α inhibitors, suggesting the need to monitor and treat such adverse effects.

Facial and neck erythema associated with dupilumab treatment: A systematic review.

BACKGROUND: Neither dupilumab-associated facial erythema nor neck erythema was reported in phase 3 clinical trials for the treatment of atopic dermatitis, but there have been a number of reports of patients developing this adverse event in clinical practice. OBJECTIVE: To outline all cases of reported dupilumab-associated facial or neck erythema to better characterize this adverse event, and identify potential etiologies and management strategies. METHODS: A search was conducted on EMBASE and PubMed databases. Two independent reviewers identified relevant studies for inclusion and performed data extraction. RESULTS: A total of 101 patients from 16 studies were reported to have dupilumab-associated facial or neck erythema. A total of 52 of 101 patients (52%) had baseline atopic dermatitis facial or neck involvement and 45 of 101 (45%) reported different cutaneous symptoms from preexisting atopic dermatitis, possibly suggesting a different etiology. Suggested etiologies included rosacea, allergic contact dermatitis, and head and neck dermatitis. Most commonly used treatments included topical corticosteroids, topical calcineurin inhibitors, and antifungal agents. In the 57 patients with data on the course of the adverse events, improvement was observed in 29, clearance in 4, no response in 16, and worsening in 8. A total of 11 of 101 patients (11%) discontinued dupilumab owing to this adverse event. LIMITATIONS: Limited diagnostic testing, nonstandardized data collection and reporting across studies, and reliance on retrospective case reports and case series. CONCLUSION: Some patients receiving dupilumab develop facial or neck erythema that differs from their usual atopic dermatitis symptoms. Prompt identification and empiric treatment may minimize distress and potential discontinuation of dupilumab owing to this adverse event.

Emerging paradigm shift toward proactive topical treatment of psoriasis: A narrative review.

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D3 analogs. Evidence-based guidelines on optimal treatment targets and maintenance therapy regimens are currently lacking. This review explores the evidence supporting approaches to maintenance topical therapy for PsO including continuous long-term therapy, chronic intermittent use, step-down therapy, sequential or pulse therapy regimens, and proactive maintenance therapy. Several unaddressed questions are discussed including how and when to transition from acute to maintenance therapy, strategies for monitoring long-term treatment, the role of topical maintenance therapy in the context of systemic and biologic therapies, risks of maintenance therapy, prescribing a topical preparation suitable for patients' preferences and skin type, and key concepts for patient education to maximize long-term outcomes. Overall, emerging evidence supports a paradigm shift toward proactive treatment once skin is completely clear as a strategy to enhance disease control without compromising safety.

Drugs associated with development of porokeratosis: A systematic review.

Porokeratosis is a rare disorder characterized by atrophic macules or patches, with a well-defined ridge-like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug-induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug-induced porokeratosis in MEDLINE and Embase in June 2020. After full-text review, 25 studies were included for analysis. We identified 26 patients with drug-induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large-scale studies are required to confirm our findings and further explore the pathogenesis for drug-induced porokeratosis.

Drugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review.

BACKGROUND: Palmoplantar keratoderma (PPK) are a heterogenous group of hereditary and acquired disorders that are characterized by excessive epidermal thickening of the palms and/or soles. PPK has been described as a rare adverse event for some medications. The aim of this systematic review was to summarize outcomes in PPK associated with various medications. This data will assist dermatologists and other healthcare providers treating patients with drug-induced PPK. METHODS: EMBASE and MEDLINE databases were searched in accordance with PRISMA guidelines using the keyword "palmoplantar keratoderma." 40 studies met the inclusion criteria. RESULTS: A total of 247 patients (mean age: 57.0 years) were included in the analysis. Among patients whose sex was reported, 60.3% (n = 35/58) were male. PPK most frequently developed after treatment with BRAF inhibitors (73.7%, n = 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, n = 38/247), tyrosine kinase inhibitors (TKIs) (3.2%, n = 8/247), or chemotherapy (2.4%, n = 6/247). The mean latency period between initiation of the drug and onset of PPK was 7.6 months (range: 0.25-90 months). Improvement of PPK was reported in 24 cases, with 50% (n = 12/24) achieving complete resolution and 50% (n = 12/24) achieving partial resolution. All patients who achieved complete resolution stopped the suspected drug, with a mean resolution period of 2.4 months (range: 2 weeks-6 months). The most common treatments for PPK were keratolytic treatments (n = 10) and topical corticosteroids (n = 4). CONCLUSIONS: PPK was most frequently associated with targeted kinase inhibitors, specifically BRAF, MEK1/2, and tyrosine kinase inhibitors.