TNF-Alpha Inhibitors and Ustekinumab for the Treatment of Psoriasis: Therapeutic Utility in the Era of IL-17 and IL-23 Inhibitors

Psoriasis is a chronic inflammatory condition for which eleven FDA-approved biologic therapies are approved. Over the past decade, studies have documented the higher efficacy of IL-17 and IL-23 inhibitors for the treatment of psoriasis compared to the TNF-alpha inhibitors and ustekinumab, an IL-12/23 inhibitor. Despite this, there remains an important role for the use of TNF-alpha inhibitors and ustekinumab in the treatment of psoriasis. Here, we review how considerations of infection and malignancy risk, patient demographics, treatment resistance, and comorbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups.

Psoriatic Onycho-Pachydermo-Periostitis

Psoriatic onycho-pachydermo-periostitis (POPP) is an unfamiliar and poorly recognised condition first described in 1989 by Fournie et al. It is a variant of psoriatic arthritis comprising the triad of onycholysis, soft tissue thickening and radiographically apparent periostitis. Whilst typically affecting the great toe, any of the digits of the hands and feet may be affected. A ‘drumstick’ appearance to the digits of the foot is the most common clinical presentation and can be extremely painful. Nail changes are another hallmark of POPP and can be mistakenly diagnosed as fungal infection leading to lengthy periods of incorrect treatment. In this article, we will outline the clinical presentation, imaging features, pathogenesis and treatment options for POPP. Currently, the existence of POPP is not widely known. Awareness of this unusual condition will allow early appropriate treatment and can aid in the diagnosis of indeterminate seronegative disease.

A Retrospective Study on the Effectiveness of Ixekizumab After Treatment With Secukinumab for Patients With Active Psoriatic Arthritis

Objectives: This study aims to evaluate clinical responses in patients with active psoriatic arthritis who, despite secukinumab 300 mg subcutaneous monthly, are switched to ixekizumab 80 mg subcutaneous every four weeks. Methods: We conducted a chart review of adult patients with psoriatic arthritis treated at one clinical center. We identified all patients with active inflammatory arthritis who were switched from secukinumab to ixekizumab. Baseline demographics such as disease duration, age, gender, number of previous DMARDs, and previous time on secukinumab were collected. We collected clinical outcome data such as tender and swollen joint count, enthesitis based on SPARCC score, dactylitis, psoriasis severity, CRP, and BASDAI if axial involvement was present. Results: Eight of 10 patients were included in the analysis. Most patients were female, average age 62 years old, and had been on secukinumab for an average of 79 weeks. Twelve weeks following switch to ixekizumab, 6/8 had improvement in tender joint count, 6/8 improved in swollen joint count, 2/2 had resolution of enthesitis, 4/4 had resolution of dactylitis, 5/6 had improvement in psoriasis severity, 1 patient had absolute improvement of 2.3 in BASDAI, and 7/8 had improvement in the CRP level. Conclusions: Patients with active psoriatic arthritis despite treatment with secukinumab may still have a clinical response following treatment with another anti-IL17 agent. Larger studies will be required to confirm this finding, and studies which emphasize dactylitis and enthesitis outcomes will be needed as most patients did not have activity in these domains.

The Role of Pain in the Lives of Patients with Psoriasis: A Qualitative Study on an Inadequately Addressed Symptom

Background: Patients with psoriasis commonly report experiencing severe sensory symptoms, and the burden of these symptoms can extend beyond unpleasant experiences to impair patients’ health-related quality of life (HRQL). However, the symptom of pain and its consequences are still poorly understood in psoriasis patients. Objective: To understand the quality and intensity of pain associated with psoriasis as well as its interference with daily function in patients with psoriasis. Methods: Three focus groups and four interviews with psoriasis patients were conducted (n = 25). A trained facilitator used a semi-structured interview guide based on a literature review and a theory-driven approach. Two researchers independently coded the narratives and reached a consensus on the major themes using NVivo 12 software. Results: Our analysis produced five main themes regarding pain. (1) Perception of pain was illustrated through intense descriptors. (2) Patients identified pain triggers, including self-inflicted triggers. (3) Patients found coping strategies to deal with pain, including suppression of sensory experience. (4) Emotional suffering was linked primarily to the compulsion to continue scratching despite repeated efforts to stop and the failure of physicians to acknowledge the burden of the pain, which led to inadequate pain management. (5) Pain led to an overt impact on HRQL in these patients through interference with daily activity, intimate relationships, and sleep. Conclusions: Pain can be a significant hardship for patients with psoriasis. We encourage clinicians to inquire about pain separate from pruritus and to consider HRQL impacts of their patients’ pain when determining treatments.

Likelihood of COVID-19 Vaccination Among Individuals Living With Psoriatic Disease: Results From a Large Real-World Survey

Introduction: Development and dissemination of novel COVID-19 vaccines represent an opportunity to end the COVID-19 pandemic by vaccinating an estimated 80% of the population. Objectives: This study examines perceptions, and demographic and clinical factors influencing the likelihood of adults with psoriasis receiving a novel COVID-19 vaccine. Methods: A cross sectional study conducted from October–November 2020 of 1405 adults with psoriatic disease with prior contact to a patient advocacy organization. The main outcome of interest was the likelihood of receiving a COVID-19 vaccine. Chi-square tests and logistic regression examined the relationship between individual characteristics and likelihood of receiving a COVID-19 vaccine. Results: Most participants (65%) received a flu vaccination in the last 12 months and were (64.2%) likely to receive a COVID-19 vaccine, while 35.9% reported being unlikely receive a vaccine. Likelihood of COVID-19 vaccination was associated with receiving the flu vaccine, race, ethnicity, sex, BMI, age, income, severity of PsO and PsA. When controlling for ethnicity, race, male sex, overweight/obese status, age, biologic use, disease type, comorbidities linked with worse COVID-19 outcomes, PsA symptoms, and skin disease severity, individuals who received the flu vaccine and those with annual household income over $75,000 were most likely to receive a COVID-19 vaccine. Conclusions: Vaccine hesitancy among individuals with psoriatic disease is considerable. Dermatologists and rheumatologists can increase COVID-19 vaccine uptake by actively engaging their patients on this topic using guidance published by the National Psoriasis Foundation on the management of psoriatic disease during the COVID-19 pandemic.

Acute Respiratory Distress Syndrome in a Carrier of an Interleukin-36 Receptor Antagonist Mutation With Generalized Pustular Psoriasis

Background Generalized pustular psoriasis of von Zumbusch is a rare variant of psoriasis often accompanied by systemic, sometimes life-threatening, symptoms. Generalized pustular psoriasis sometimes arises in pregnancy. Case report A 31-year-old female, with a history of schizophrenia and recurrent episodes of gestation-associated pustular psoriasis, was admitted to our department because of a generalized pustular rash during the 22nd week of her fifth pregnancy. Clinical and histopathological examinations were suggestive of generalized pustular psoriasis (von Zumbusch type). During this hospitalization, she developed acute dyspnea, fever, tachycardia, and marked leukocytosis. An extensive workup failed to reveal an infectious, cardiac, or pulmonary abnormality, while severe respiratory distress necessitated mechanical ventilation. Radio-imaging revealed diffuse alveolar infiltrates consistent with acute respiratory distress syndrome (ARDS). In the absence of any other plausible cause, ARDS was considered as secondary to her skin disease. Genetic base was suspected, and genetic analysis uncovered a novel mutation in IL36RN encoding the IL-36 receptor antagonist. Only 15 cases of ARDS secondary to psoriasis have been described to date. This is the first report of this very rare complication in a known carrier of an IL36RN mutation. The fact that IL36RN is abundantly expressed in the lung as well as in the epidermis may underlie the unusual clinical features of this dramatic case. Conclusion The present case suggests the need to carefully monitor patients with pregnancy-associated generalized pustular psoriasis for possible life-threatening pulmonary complications and the possible link to IL36RN mutation.

Healthcare Providers Face Numerous Challenges in Treating Patients with Psoriasis: Results from a Mixed-Methods Study

Background The paradigm shift toward biologic medications in psoriasis care requires healthcare providers (HCPs) to become acquainted with mechanisms of action and safety profiles of these new treatments to confidently use them in practice. A better understanding of this paradigm shift is necessary to provide adequate education for HCPs in psoriasis care. Objectives This study assessed clinical practice gaps and challenges experienced by HCPs caring for patients with psoriasis. Methods A mixed-methods approach was used to identify practice gaps and clinical challenges of dermatologists, rheumatologists, primary care physicians, physician assistants, and nurse practitioners with various levels of clinical experience in academic and community-based settings. Qualitative and quantitative data were collected sequentially. Interviews were transcribed and thematically analyzed. Results A total of 380 psoriasis care providers in Canada and the US participated in this study. Analysis revealed challenges in establishing an accurate diagnosis of psoriasis (including screening for sub-type and distinguishing psoriasis from other skin conditions), selecting treatment (particularly regarding recently approved treatments), monitoring side effects, and collaborating with other HCPs involved in psoriasis care. Conclusion These findings highlight educational needs of HCPs involved in psoriasis care that could have repercussions on accurate and timely diagnosis of the condition, treatment initiation, side effect monitoring, and continuity of care. Findings provide a starting point for clinicians to reflect on their practice and for the improvement of continuing professional development interventions that would bridge these gaps.

Antibody Response to BNT162b2 Vaccine in Immune Modifiers–Treated Psoriatic Patients

Background Data regarding anti–COVID-19 vaccination efficacy in psoriasis patients treated with immune-modulatory medications are scarce. Objective This study aims to examine the rate of positive antibody response following BNT162b2 vaccine in those patients. Methods BNT162b2-vaccinated and immune modifier–treated psoriatic patients were assigned to serological testing of IgG antibodies to protein S of SARS-CoV-2 after the second vaccination dose by Abbott Architect or Beckman Coulter. Levels ≥ 1 S1 units/mL (S/ml) and > 150 arbitrary units/ml (AU/ml) are considered a positive antibody response, respectively. The antibody levels further analyzed according to the patient’s characteristics and compared to health workers’ controls. Results Forty-nine of the 51 patients had a positive antibody response. Overall, patients treated with immune-modulatory medications had antibody levels similar to the control group. Conclusions Immune modifier–treated psoriasis patients seem to develop a positive antibody response to the full BNT162b2 vaccination in the vast majority of cases.