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.

Stevia and Uncaria extract (GlucoMedix®) reduces glucose levels and the need for medications in type 2 diabetes: an open label case series of six patients

Background GlucoMedix® is an all-natural phytotherapy consisting of a hydro-alcoholic extract of Stevia rebaudiana (Bertoni) Bertoni and pentacyclic chemotype Uncaria tomentosa (Willd. Ex Schult.) DC. The nutraceutical product has potential for the treatment of hyperglycemia in type 2 diabetes and Metabolic Syndrome. Methods Six adult Hispanic type 2 diabetic patients were included in an outpatient retrospective open label physician-sponsored case series study. GlucoMedix® extract of Stevia plus pentacyclic chemotype Uncaria was administered orally at doses of 2 ml, diluted in water, two or three times daily. The patients’ blood glucose levels were recorded historically, at baseline, and thereafter while taking GlucoMedix® orally. Results When treated with GlucoMedix®, with or without coincident advice to modify diet, all six patients manifested reductions in blood glucose levels. At baseline four of the six patients were administering one or more prescription treatments for hyperglycemia, e.g., Glibenclamide, Metformin, Vildagliptin, or Insulin. Two patients displayed substantial reductions in glucose of 50 and 70 mg/dl, and in conjunction with the removal of their prior drug treatments of Glibenclamide plus Metformin or of Vildagliptin. An Insulin-treated patient experienced a 50 mg/dl reduction while ceasing Metformin and was subsequently able to reduce the dose of Insulin by half. Thus, in three patients GlucoMedix® abrogated in whole or in part the requirement for pharmaceutical or biologic therapies to achieve substantial beneficial reductions in glycemic levels. Conclusions In this proof-of-principle study oral GlucoMedix® was an effective treatment for hyperglycemia in type 2 diabetic individuals. This all-natural phytotherapy can be used beneficially in conjunction with existing pharmaceutical or biological therapy regimens, and in some cases can replace in whole or in part the requirement for pharmaceutical or biologic therapies. These in-life results suggest that this natural product approach can serve as an alternative to prescription monotherapies or multimodal therapies for the regulation of hyperglycemia.

COVID-19 Vaccine Hesitancy among Patients with Inflammatory Bowel Disease Receiving Biologic Therapies in Kuwait: A Cross-Sectional Study

Background: COVID-19 vaccinations have been shown to be effective in reducing risk of severe infection, hospitalization, and death. They have also been shown to be safe and effective in patients with inflammatory bowel disease (IBD) who are receiving biologic therapies. In this study, we aimed to evaluate the prevalence of vaccination among patients receiving biologic therapies for IBD. Methods: A single-center prospective cross-sectional study conducted at a tertiary care inflammatory bowel disease center in Kuwait. Data from patients with inflammatory bowel disease (IBD) who attended the gastroenterology infusion clinic from 1 June 2021 until 31 October 2021 were retrieved. Patients who received infliximab or vedolizumab at least six weeks before recruitment were included. The primary outcome was prevalence of COVID-19 vaccination. The secondary outcome was to assess whether prevalence of COVID-19 vaccination differed based on sex, age, type of biologic therapy and nationality. Results: The total number of inflammatory bowel disease (IBD) patients enrolled in the study was 280 (56.0% male and 44.0% female). Of the total, 112 (40.0%) patients were diagnosed with ulcerative colitis and 168 (60.0%) with Crohn’s disease. The number of ulcerative colitis patients who were vaccinated was 49 (43.8%) and the number of Crohn’s disease patients who were vaccinated was 68 (40.5%). The median age was 33.2 years and BMI was 24.8 kg/m2. With respect to the total number of patients, 117 (41.8%) were vaccinated with either BNT162b2 or ChAdOx1 nCoV-19 and 163 (58.2%) were not vaccinated. Female patients were more likely to receive the vaccine compared to male patients (83.0% vs. 63.8%, p < 0.001). In addition, patients above the age 50 were more likely to receive the vaccine than patients below the age of 50 (95.6% vs. 31.2% p < 0.001). Expatriates were more likely to receive the vaccine than citizens (84.8% vs. 25.0%, p < 0.001). There was no statistical difference between patients on infliximab and vedolizumab with regard to prevalence of vaccination (40.0% vs 48.0%, p = 0.34). Conclusion: The overall prevalence of COVID-19 vaccination among patients with inflammatory bowel disease (IBD) on biologic therapies was lower than that of the general population and world health organization (WHO) recom-mendation. Female patients, patients above the age of 50, and expatriates were more likely to receive the vaccine. Physicians should reinforce the safety and efficacy of COVID-19 vaccines among patients, especially IBD patients on biologic therapies, who express hesitancy towards them.

Guselkumab Treatment Outcomes and Persistence in a Nationwide Real-world Cohort of Patients with Plaque Psoriasis

Guselkumab treatment outcomes and persistence were assessed in a real-world cohort of Finnish patients with difficult-to-treat plaque psoriasis over a median follow-up of 1 year. Data on 181 patients who initiated guselkumab at the 15 study centres were collected retrospectively from the patient charts. Prior exposure to biologic therapies was common with 56% and 35% having used at least 1 and 2 biologics, respectively. Median guselkumab treatment duration was 11 months with 21 patients (12%) discontinuing treatment during follow-up. Of 85 patients with a follow-up duration of at least 1 year, 73 (86%) were still on guselkumab at 1 year. Significant improvements during follow-up were seen in the absolute Psoriasis Area and Severity Index (PASI) scores with 32 patients (80%) having absolute PASI ≤ 2 after a 9–14-month treatment. Guselkumab treatment was effective and treatment persistence was high in the nationwide Finnish real-life setting.

Serological Response to BNT162b2 and ChAdOx1 nCoV-19 Vaccines in Patients with Inflammatory Bowel Disease on Biologic Therapies

Introduction: The immunogenicity of SARS-CoV-2 vaccines in patients with inflammatory bowel disease (IBD) on biologic therapies is not well studied. The goal of this study was to measure the serological response to BNT162b2 and ChAdOx1 nCoV-19 vaccines in patients with IBD receiving different biologic therapies. Methods: We performed a multi-center prospective study between 1 August 2021 and 15 September 2021. We measured the seropositivity of SARS-CoV-2 antibodies (SARS-CoV-2 IgG) and neutralizing antibody concentrations in patients with IBD receiving biologic therapies 4–10 weeks after their second dose or 3–6 weeks after their first dose of BNT162b2 or ChAdOx1 nCoV-19 vaccines. Results: A total of 126 patients were enrolled (mean age, 31 years; 60% male; 71% Crohn’s disease, 29% ulcerative colitis). Of these, 92 patients were vaccinated with the BNT162b2 vaccine (73%) and 34 patients with the ChAdOx1 nCoV-19 vaccine (27%). In patients being treated with infliximab and adalimumab, the proportion of patients who achieved positive anti-SARS-CoV-2 IgG antibody levels after receiving two doses of the vaccine were 44 out of 59 patients (74.5%) and 13 out of 16 patients (81.2%), respectively. In contrast, of those receiving ustekinumab and vedolizumab, the proportion of patients who achieved positive anti-SARS-CoV-2 IgG antibody levels after receiving two doses of the vaccine were 100% and 92.8%, respectively. In patients receiving infliximab and adalimumab, the proportion of patients who had positive anti-SARS-CoV-2 neutralizing antibody levels after two-dose vaccination was 40 out of 59 patients (67.7%) and 14 out 16 patients (87.5%), respectively. On the other hand, the proportion of patients who had positive anti-SARS-CoV-2 neutralizing antibody levels were 12 out of 13 patients (92.3%) and 13 out of 14 patients (92.8%) in patients receiving ustekinumab and vedolizumab, respectively. Conclusions: The majority of patients with IBD who were on infliximab, adalimumab, and vedolizumab seroconverted after two doses of SARS-CoV-2 vaccination. All patients on ustekinumab seroconverted after two doses of SARS-CoV-2 vaccine. The BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines are both likely to be effective after two doses in patients with IBD on biologics. Larger follow-up studies are needed to evaluate if decay of antibodies occurs over time.

Retrospective Database Analysis: Dose Escalation and Adherence in Patients Initiating Biologics for Ulcerative Colitis

Background: Biologic therapies are often used in patients with ulcerative colitis who are non-responsive to conventional treatments. However, non-response or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with ulcerative colitis in the USA. Methods: This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with ulcerative colitis initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. Results: Of 2,331 patients included in the study (adalimumab [N=1,291], infliximab [N=810], golimumab [N=127], vedolizumab [N=103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred $20,106 higher total ulcerative colitis-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration=112 days). Conclusion: Dose escalation was common, and incurred higher costs, in patients with ulcerative colitis initiating biologic therapies. Sub-optimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients.

COVID-19 Vaccine Hesitancy Among Patients with Inflammatory Bowel Disease on Biologic Therapies; A cross-sectional study

BackgroundCOVID-19 Vaccinations have been shown to be effective in reducing risk of severe infection, hospitalization, and death. They also have been shown to be safe and effective in patients with inflammatory bowel disease (IBD) on biologic therapies. In this study, we aimed to evaluate the prevalence of vaccination among patients with IBD on biologic therapies.MethodsA single-center prospective cross-sectional study conducted at a tertiary care inflammatory bowel disease center. Data from patients with inflammatory bowel disease (IBD) who attended the gastroenterology infusion clinic from June 1st, 2021 until October 31st, 2021 were retrieved. Patients received infliximab or vedolizumab at least 6 weeks before recruitment were included. The primary outcome was prevalence of COVID-19 vaccination. The secondary outcome was to assess whether prevalence of COVID-19 vaccination differed based sex, age, type of biologic therapy and citizenship status.ResultsThe total number of inflammatory bowel disease (IBD) patients enrolled in the study was 280 (56.0% male and 44.0% female). The median age was 33.2 years and BMI was 24.8 kg/m2. 112 patients with ulcerative colitis (40.0%) and 168 (60.0%) with Crohn’s disease. 117 (41.8%) were vaccinated with either BNT162b2 or ChAdOx1 nCoV-19 and 163 (58.2%) were not vaccinated. Female patients were more likely to receive the vaccine compared to male patients (83.0% vs. 63.8%, p < 0.001). In addition, older patients (above the age 50) were also more likely to receive the vaccine than younger patients, below the age of 50 (95.6% vs 31.2% p< 0.001). Expatriates were more likely to receive the vaccine than citizens (84.8% vs 25.0%, p < 0.001). There was no statistical difference between patients on Infliximab and vedolizumab in terms of prevalence of vaccination (40.0% vs 48.0%, p= 0.34).ConclusionThe overall prevalence of COVID-19 vaccination among patients with inflammatory bowel disease (IBD) on biologic therapies was lower than the general population and world health organization (WHO) recommendation. Female patients, patients above the age of 50, and expatriates were more likely to be vaccinated. On the other hand, male patients, patients below the age of 50, and citizens were less likely to be vaccinated.

An update on the adalimumab biosimilar landscape following the approval of the first high-concentration biosimilar

Biosimilars can reduce healthcare costs and expand patient access to biologic therapies. Currently, eight adalimumab biosimilars have received regulatory approval from the EMA and/or the US FDA. Following recent EMA approval of the first high-concentration adalimumab biosimilar, CT-P17, this review provides a contemporary update on adalimumab biosimilars currently licensed in Europe and the USA. The totality of evidence from each clinical development program is summarized, and characteristics of each formulation and/or device that potentially affect the convenience of treatment for patients are discussed. Future perspectives are considered, including the potential impact of the FDA’s first interchangeability designation for an adalimumab biosimilar, ahead of their entry into the US marketplace in 2023.

Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder

Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.