Response to ritlecitinib with or without narrow-band UVB add-on therapy in patients with active nonsegmental vitiligo: results from a phase 2b extension study.

Background: Ritlecitinib demonstrated efficacy in a phase 2b trial of nonsegmental vitiligo.

Objective: To evaluate the efficacy and tolerability of ritlecitinib with add-on narrow-band UVB (nbUVB) phototherapy in patients with nonsegmental vitiligo.

Methods: Following a 24-week, placebo-controlled, dose-ranging period, patients received ritlecitinib 200mg for 4 weeks then 50mg for 20 weeks, with or without nbUVB phototherapy 2x/week.

A phase 2a trial of brepocitinib for cicatricial alopecia.

Background: Cicatricial alopecias are chronic, progressive scarring hair-loss conditions. Molecular dysregulation is not fully understood, hindering treatment development. Th1/IFNγ signaling and Janus kinase dysregulation has shown involvement, providing rationale for this phase 2a trial with Tyrosine kinase 2/Janus kinase 1 inhibitor brepocitinib.

Hair regrowth in alopecia areata and re-pigmentation in vitiligo in response to treatment: Commonalities and differences.

Both alopecia areata (AA) and vitiligo share common pathogenesis involving, interferon-γ (IFN-γ) and interleukin-15 (IL-15) signalling pathways that activate cytotoxic CD8+ T lymphocytes. These shared mechanisms may explain why both diseases respond to currently available treatments (e.g.

Exploratory pharmacodynamics and efficacy of PF-06817024 in a Phase 1 study of patients with chronic rhinosinusitis and atopic dermatitis.

PF-06817024 is a humanized antibody against interleukin-33 that has the potential to inhibit type 2 inflammation. An exploratory analysis of the pharmacodynamics and clinical effects of single and repeat doses of PF-06817024 was assessed in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and patients with moderate-to-severe atopic dermatitis (AD), respectively, as part of a Phase 1, first-in-human study. Rhinosinusitis symptoms were improved, and nasal polyps were decreased in size following treatment with PF-06817024 in patients with CRSwNP.

A Phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study to evaluate the safety and pharmacokinetics/pharmacodynamics of PF-06835375, a C-X-C chemokine receptor type 5 directed antibody, in patients with systemic lupus erythematosus or rheumatoid arthritis.

Background: The objective of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PF‑06835375, a potent selective afucosyl immunoglobulin G1 antibody targeting C-X-C chemokine receptor type 5 (CXCR5) that potentially depletes B cells, follicular T helper (Tfh) cells, and circulating Tfh-like (cTfh) cells, in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods: This first-in-human, multicenter, double-blind, sponsor-open, placebo-controlled Phase 1 study recruited patients aged 18-70 years with SLE or RA. In Part A, patients received single doses of intravenous PF-06835375 (dose range: 0.

Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences.

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.

Master protocols and other innovative trial designs in inflammation and immunology to expedite clinical drug development.

Master protocol designs, such as umbrella and basket studies, allow multiple compounds or multiple target populations to be evaluated simultaneously within a single protocol, and have been widely adopted in oncology clinical trials. These novel designs can also be applied in other therapeutic areas, where they could have several benefits over conducting traditional randomized controlled trials. Here, we detail Pfizer's recent implementations of master protocol designs in inflammation and immunology clinical studies, focusing on the opportunities for cost and resource savings and how these designs can expedite the time required to bring new treatments to patients in need.

Demographics, clinical characteristics, and treatment patterns among keloid patients: United States Electronic Health Records (EHR) Database Study.

Introduction: There is limited epidemiologic evidence on keloids using real-world data, especially in the United States (US) across race and ethnicity.

Methods: We conducted a retrospective cohort study using Cerner Real-World Data, between 2015 and 2021, to describe the demographic and clinical characteristics of US adults with keloids. Keloids were identified using a combination of ICD-10 and (Systemized Nomenclature of Medicine-Clinical Terms [SNOMED] codes).

Brepocitinib, Zimlovisertib, and Ropsacitinib in Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disease with limited treatment options and partially understood pathophysiology. Using an umbrella trial design, three kinase inhibitor immunomodulators with different mechanisms of action were evaluated. METHODS: This phase 2a, double-blind, parallel-group trial enrolled adults with moderate to severe HS who were then randomly assigned (1:1:1:1) to once-daily brepocitinib 45 mg (a JAK1/TYK2 inhibitor), zimlovisertib 400 mg (an IRAK4 inhibitor), ropsacitinib 400 mg (a TYK2 inhibitor), or matching placebo for 16 weeks.

Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis: A Randomized Clinical Trial.

Importance: Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions.

Objective: To assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis.

Design, Setting, And Participants: This phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries.

Natural History of Keloids: A Sociodemographic Analysis Using Structured and Unstructured Data.

Introduction: Keloids are lesions characterized by the growth of dense fibrous tissue extending beyond original wound boundaries. Research into the natural history of keloids and potential differences by sociodemographic factors in the USA is limited. This real-world, retrospective cohort study aimed to characterize a population of patients with keloids compared with matched dermatology and general cohorts.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PF-06817024 in Healthy Participants, Participants with Chronic Rhinosinusitis with Nasal Polyps, and Participants with Atopic Dermatitis: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study.

PF-06817024 is a high affinity, humanized antibody that binds interleukin-33, a proinflammatory type 2 cytokine, and thereby has the potential to inhibit downstream type 2 inflammation. This Phase 1, randomized, placebo-controlled study was conducted in 3 parts to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics of escalating single and limited repeat PF-06817024 doses in healthy participants (Part 1), a single dose of PF-06817024 in participants with chronic rhinosinusitis with nasal polyps (Part 2), and repeat doses of PF-06817024 in participants with moderate to severe atopic dermatitis (atoptic dermatitis; Part 3). PF-06817024 was generally well tolerated in all participant populations.

Role of Innate Immunity in Allergic Contact Dermatitis: An Update.

Our understanding of allergic contact dermatitis mechanisms has progressed over the past decade. Innate immune cells that are involved in the pathogenesis of allergic contact dermatitis include Langerhans cells, dermal dendritic cells, macrophages, mast cells, innate lymphoid cells (ILCs), neutrophils, eosinophils, and basophils. ILCs can be subcategorized as group 1 (natural killer cells; ILC1) in association with Th1, group 2 (ILC2) in association with Th2, and group 3 (lymphoid tissue-inducer cells; ILC3) in association with Th17.

Efficacy and Safety of the TYK2/JAK1 Inhibitor Brepocitinib for Active Psoriatic Arthritis: A Phase IIb Randomized Controlled Trial.

Objective: Brepocitinib is a TYK2/JAK1 inhibitor in development for the treatment of several immunologic diseases. The efficacy and safety of oral brepocitinib were assessed in participants with moderately-to-severely active psoriatic arthritis (PsA) for up to 52 weeks.

Methods: In this placebo-controlled, dose-ranging, phase IIb study, participants were randomized to receive 10 mg, 30 mg, or 60 mg of brepocitinib once daily or placebo, advancing to 30 mg or 60 mg of brepocitinib once daily at week 16.

Efficacy and safety of topical brepocitinib cream for mild-to-moderate chronic plaque psoriasis: a phase IIb randomized double-blind vehicle-controlled parallel-group study.

Background: Plaque psoriasis (PsO) is an inflammatory skin disease driven, in part, by the activation of Janus kinase (JAK) signalling pathways.

Objectives: To assess the efficacy and safety of multiple doses of topical brepocitinib, a tyrosine kinase 2/JAK1 inhibitor, in participants with mild-to-moderate PsO.

Methods: This phase IIb multicentre randomized double-blind study was conducted in two stages.

A shared tissue transcriptome signature and pathways in psoriasis and ulcerative colitis.

Despite multiple efficacious therapies in common between psoriasis (PS) and Ulcerative Colitis (UC), mechanisms underlying their common pathophysiology remain largely unclear. Here we sought to establish a link by evaluating expression differences and pathway alterations in diseased tissues. We identified two sets of differentially expressed genes (DEGs) between lesional and nonlesional tissues in meta-analyses of data collected from baseline samples in 3 UC and then 3 PS available clinical studies from Pfizer.