Biologic therapies associated with development of palmoplantar pustulosis and palmoplantar pustular psoriasis: a systematic review.

BACKGROUND: Palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) are chronic inflammatory skin conditions characterized by eruptions of sterile pustules on the palms and/or soles. Biologic use has been associated with PPP and PPPP development in the literature. OBJECTIVES: To identify PPP and PPPP associated with biologics and summarize reported treatments and outcomes. METHODS: We systematically searched in MEDLINE and Embase for articles that reported PPP or PPPP during biologic treatment. After a full-text review, 53 studies were included for analysis. RESULTS: We identified 155 patients with PPP/PPPP onset during biologic treatment, with a mean age of 44.1 years and a female preponderance (71.6%). The most frequently reported biologics were adalimumab (43.9%) and infliximab (33.3%). IL-17 inhibitors, secukinumab (7.6%) and brodalumab (1.5%), were reported only in association with PPPP. Overall, 58.8% of patients had complete remission (CR) in 3.6 months and 23.5% had partial remission (PR) in 3.7 months. The most common treatments that led to CR were topical corticosteroids (n = 16) and biologic switching (n = 8). CONCLUSIONS: Clinicians should anticipate PPP or PPPP as potential drug reactions to biologics such as adalimumab and infliximab. Large-scale studies are required to confirm our findings and further explore the pathogenesis for biologic-associated PPP and PPPP.

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.

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.

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.

Management of Plaque Psoriasis With Biologic Therapies in Women of Child-Bearing Potential Consensus Paper.

BACKGROUND: Plaque psoriasis (PsO) is a chronic inflammatory disease that often presents at peak reproductive age in women of child-bearing potential (WOCBP). With the emergence of biologic therapies to treat PsO, guidance on disease management in WOCBP is needed to inform treatment decisions before, during, and after pregnancy. OBJECTIVES: To develop a practical, up-to-date consensus document, based on available evidence and expert opinion where evidence was lacking, in order to guide both Canadian and international clinicians treating PsO in WOCBP. METHODS: A panel of 9 Canadian dermatologists with extensive clinical experience managing PsO reviewed the relevant literature from the past 25 years in 3 key domains: overview of PsO in WOCBP and clinical considerations, treatment considerations, and postpartum considerations. The structured literature search focused on WOCBP treated with TNF-alpha inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab), IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), IL-12/23 inhibitors (ustekinumab), and IL-17 inhibitors (brodalumab, ixekizumab, secukinumab). This literature review, along with clinical expertise and opinion, was used to develop concise and clinically relevant consensus statements to guide practical management of PsO in WOCBP. Experts voted on the statements using a modified Delphi process and prespecified agreement cut-off of 75%. RESULTS AND IMPLICATIONS: After review, discussion, and voting on 19 draft consensus statements at an in-person meeting and remotely, 12 consensus statements were approved by the expert panel. The statements presented here will guide healthcare providers in practical disease management using biologic therapies for the treatment of PsO in WOCBP.

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section IV: Treatment Options for the Management of Atopic Dermatitis.

The objectives of therapy for atopic dermatitis (AD) are to reduce skin inflammation and pruritus, restore skin barrier function, and improve quality of life (QoL). Treatments can be classified as moisturizing and basic care, topical therapy, phototherapy, and systemic therapy. In this review, we summarize the treatments for AD and recommendations for their use.

Diagnosis and management of psoriasis.

OBJECTIVE: To provide primary care clinicians with an up-to-date and practical overview of the diagnosis and management of psoriasis. QUALITY OF EVIDENCE: PubMed, MEDLINE, EMBASE, and Cochrane databases were searched for relevant meta-analyses, randomized controlled trials, systematic reviews, and observational studies about the diagnosis and management of psoriasis. MAIN MESSAGE: Psoriasis is a chronic, multisystem inflammatory disease with predominantly skin and joint involvement. Beyond the physical dimensions of disease, psoriasis has an extensive emotional and psychosocial effect on patients, affecting social functioning and interpersonal relationships. As a disease of systemic inflammation, psoriasis is associated with multiple comorbidities, including cardiovascular disease and malignancy. The diagnosis is primarily clinical and a skin biopsy is seldom required. Depending on the severity of disease, appropriate treatment can be initiated. For mild to moderate disease, first-line treatment involves topical therapies including corticosteroids, vitamin D3 analogues, and combination products. These topical treatments are efficacious and can be safely initiated and prescribed by primary care physicians. Patients with more severe and refractory symptoms might require further evaluation by a dermatologist for systemic therapy. CONCLUSION: Many patients with psoriasis seek initial evaluation and treatment from their primary care providers. Recognition of psoriasis, as well as its associated medical and psychiatric comorbidities, would facilitate timely diagnosis and appropriate management with effective and safe topical therapies and other medical and psychological interventions, as needed. More severe and refractory cases might warrant referral to a dermatologist for further evaluation and possible systemic therapy.

MACEs Not Associated With the Use of Biologic Therapy for Psoriasis in Real-World Clinical Practice: A Canadian Multicenter Retrospective Study.

INTRODUCTION: Previous reports have shown inconsistent findings with regard to the relationship between biologic therapy and risk for major adverse cardiovascular events (MACEs). OBJECTIVES: The aim of this study was to determine the overall rate of MACEs in a cohort of 398 patients. METHODS: All patients treated with biologics for psoriasis at 2 academic centers in Toronto, Ontario, between September 2005 and September 2014 were considered for inclusion. Medical records were reviewed to identify MACEs. RESULTS: A total of 398 patients were included. The median duration of disease was 19.8 years. Median time to biologic therapy withdrawal because of an adverse event was 23.5 months. In this cohort, no MACEs were identified in patients treated with biologic therapy. CONCLUSIONS: Biologic treatment for psoriasis was not associated with increased cardiovascular risk in this cohort. These results require validation in larger studies.

Adverse events resulting in withdrawal of biologic therapy for psoriasis in real-world clinical practice: A Canadian multicenter retrospective study.

BACKGROUND: Safety profiles of biologics for treatment of psoriasis are limited to data from randomized controlled trials. There is a need for comparative safety reports of biologics based on data from clinical practice. OBJECTIVE: We sought to estimate and compare the incidence of adverse events (AEs) leading to withdrawal of biologics (etanercept, infliximab, adalimumab, and ustekinumab) in the treatment of psoriasis. METHODS: We conducted a multicenter retrospective chart review from September 2005 to September 2014. Incidence proportion and rate of AEs leading to withdrawal by biologic agent and AE were calculated. RESULTS: For 545 treatments administered in 398 patients, 22 (4.04%) AEs were associated with withdrawal, for a rate of 1.97/100 patient-years (95% confidence interval [CI] 1.32-2.94). Common AEs were injection-/infusion-site reactions (0.55%, 0.92%, 0%, and 0% for etanercept, infliximab, adalimumab, and ustekinumab, respectively); infections (0%, 0.18%, 0.55%, 0.18%); and malignancies (0.18%, 0.18%, 0%, 0.37%). LIMITATIONS: Possible incompleteness of chart details and small study population limit the conclusiveness of findings. CONCLUSION: Biologic agents for treatment of psoriasis are safe; AEs associated with withdrawal occurred in 4% of all administered biologic therapies. It does not appear that real-world patients encounter more AEs with biologics than patients in clinical trials.