Integrated Safety Analysis of Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis From the Phase II and Phase III Clinical Trial Program.

BACKGROUND: Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy. OBJECTIVE: The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study. METHODS: Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported. RESULTS: Total exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19. CONCLUSION: Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD. TRIAL REGISTRIES: ClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.

Biologic Treatment Algorithms for Moderate-to-Severe Psoriasis with Comorbid Conditions and Special Populations: A Review.

The emergence of data from clinical trials of biologics, the approval of new biologics, and our improved understanding of psoriasis pathogenesis have increased the therapeutic possibilities for the treatment of moderate-to-severe psoriasis. Biologics currently approved for the treatment of psoriasis include tumor necrosis factor inhibitors, interleukin (IL)-17 inhibitors, ustekinumab (an IL-12/23 inhibitor), and IL-23 inhibitors. Data from clinical trials and studies of the safety and efficacy of biologics provide essential information for the personalization of patient care. We discuss the benefits and disadvantages of biologics as a first-line treatment choice, update treatment recommendations according to current evidence, and propose psoriasis treatment algorithms. Our discussion includes the following comorbid conditions: psoriatic arthritis, multiple sclerosis, congestive heart failure, inflammatory bowel disease, hepatitis B, nonmelanoma skin cancer, lymphoma, and latent tuberculosis. We make evidence-based treatment recommendations for special populations, including pediatric patients, patients with coronavirus 2019 (COVID-19), and pregnant and breastfeeding patients with psoriasis. Ultimately, individualized recommendations that consider patient preferences, disease severity, comorbid conditions, and additional risk factors should be offered to patients and updated as new trial data emerges.

Coronavirus disease 2019, immune-mediated inflammatory diseases and immunosuppressive therapies - A Danish population-based cohort study.

BACKGROUND: Limited data exist regarding the disease course of coronavirus disease 2019 (COVID-19) and its relationship with immunosuppressants among patients with immune-mediated inflammatory diseases (IMIDs). Therefore, this study aims to investigate the association between COVID-19, frequent rheumatological, dermatological, gastrointestinal, and neurological IMIDs and immunosuppressants. METHODS: We conducted a Danish population-based cohort study including all residents living within Capital Region of Denmark and Region Zealand from January 28th, 2020 until September 15th, 2020 with the only eligibility criterion being a test for SARS-CoV-2 via reverse transcription-polymerase chain-reaction. Main outcomes included development of COVID-19, COVID-19-related hospitalization and mortality. RESULTS: COVID-19 was less common among patients with IMIDs than the background population (n = 328/20,513 (1.60%) and n = 10,792/583,788(1.85%), p < 0.01, respectively). However, those with IMIDs had a significantly higher risk of COVID-19-related hospitalization (31.1% and 18.6%, p < 0.01, respectively) and mortality (9.8% and 4.3%, p < 0.01, respectively), which were associated with patients older than 65 years, and presence of comorbidities. Furthermore, systemic steroids were independently associated with a severe course of COVID-19 (Odds ratio (OR) = 3.56 (95%CI 1.83-7.10), p < 0.01), while biologic therapies were associated with a reduced risk hereof (OR = 0.47 (95%CI 0.22-0.95), p = 0.04). Patients suspending immunosuppressants due to COVID-19 had an increased risk of subsequent hospitalization (OR = 3.59 (95%CI 1.31-10.78), p = 0.02). CONCLUSION: This study found a lower occurrence, but a more severe disease course, of COVID-19 among patients with IMIDs, which was associated with the use of systemic steroids for IMIDs and suspension of other immunosuppressants. This study emphasizes the importance of weighing risks before suspending immunosuppressants during COVID-19.