Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis

BACKGROUND. Antigen-specific regulation of autoimmune disease is a major goal. In seropositive rheumatoid arthritis (RA), T cell help to autoreactive B cells matures the citrullinated (Cit) antigen-specific immune response, generating RA-specific V domain glycosylated anti-Cit protein antibodies (ACPA VDG) before arthritis onset. Low or escalating antigen administration under “sub-immunogenic” conditions favors tolerance. We explored safety, pharmacokinetics, and immunological and clinical effects of s.c. DEN-181, comprising liposomes encapsulating self-peptide collagen II259-273 (CII) and NF-κB inhibitor 1,25-dihydroxycholecalciferol. METHODS. A double-blind, placebo-controlled, exploratory, single-ascending-dose, phase I trial assessed the impact of low, medium, and high DEN-181 doses on peripheral blood CII-specific and bystander Cit64vimentin59-71–specific (Cit-Vim–specific) autoreactive T cell responses, cytokines, and ACPA in 17 HLA-DRB1*04:01+ or *01:01+ ACPA+ RA patients on methotrexate. RESULTS. DEN-181 was well tolerated. Relative to placebo and normalized to baseline values, Cit-Vim–specific T cells decreased in patients administered medium and high doses of DEN-181. Relative to placebo, percentage of CII-specific programmed cell death 1+ T cells increased within 28 days of DEN-181. Exploratory analysis in DEN-181–treated patients suggested improved RA disease activity was associated with expansion of CII-specific and Cit-Vim–specific T cells; reduction in ACPA VDG, memory B cells, and inflammatory myeloid populations; and enrichment in CCR7+ and naive T cells. Single-cell sequencing identified T cell transcripts associated with tolerogenic TCR signaling and exhaustion after low or medium doses of DEN-181. CONCLUSION. The safety and immunomodulatory activity of low/medium DEN-181 doses provide rationale to further assess antigen-specific immunomodulatory therapy in ACPA+ RA

Tele-rheumatology to regional hospital outpatient clinics: patient perspectives on a new model of care

Background: Telehealth has the potential to improve access to specialist rheumatology services. The timely and appropriate delivery of care to those living with rheumatological diseases is crucial to ensuring excellent long-term outcomes. Introduction: The outcomes of a tele-rheumatology service delivered to regional hospital outpatient clinics were evaluated with patient perspectives and acceptability analyzed. Materials and Methods: A tele-rheumatology clinic was commenced in Australia from a metropolitan hospital to five regional clinics. The model of care included a trained nurse at the spoke site linked to a rheumatologist from the hospital hub site for follow-up consultations of stable review patients using videoconferencing. Surveys assessing perspectives on the tele-rheumatology encounter were completed and a subsample participated in focus groups to further explore acceptability. Results: Forty-eight patients with a diverse range of conditions participated. Patient travel was reduced on average by 95 km and 42% avoided time off work. Eighty-eight to 100% of participants agreed/strongly agreed with statements relating to acceptability, quality of physician-patient interaction, and nurse involvement. Twenty-nine percent expressed the need for a physical examination by a specialist rheumatologist and 25% felt that an in-person consultation would establish better patient-physician rapport. Qualitatively, participants viewed tele-rheumatology as equivalent to in-person care after an initial adjustment period. Discussion: Tele-rheumatology through videoconferencing for follow-up of patients with established disease is acceptable to patients and demonstrates the potential to improve time, travel, and cost burdens placed on patients who live remotely compared with traditional, face-to-face rheumatology care. Conclusions: Implementation of sustainable and patient acceptable models of tele-rheumatology care may allow timely access to all patients living with rheumatological conditions