Periodic Reporting for period 4 - RTCure (Rheuma Tolerance for Cure)
Reporting period: 2020-09-01 to 2021-08-31
An important part of our work is to achieve a better understanding of the yet unexplored phases of the disease prior to RA diagnosis. We have developed and validated new methods to identify individuals at risk for RA and developed tools to monitor disease progression. We have also expanded and further developed cohorts suitable for these purposes. Furthermore, we have also developed standard operating procedures (SOPs) for assays that are and will be used to to monitor effects of immune interventions, including tolerizing therapies that are used in clinical trials for RA. The same SOPs are and will be used in clinical trials for prevention in individuals at high risk for RA.
As described above, a major undertaking for the accomplishment of our aim is to initiate and perform clinical trials seeking tolerance induction in patients with RA-associated immunity while these individuals have not yet developed arthritis. Five such trials are ongoing (partly) within the Rheuma Tolerance for Cure project (RTCure), three have finalized recruitment and are currently subject to evaluation of results. We expect that the combined results of novel approaches to understand pathogenic immunity and efforts to modify this immunity will result in a new paradigm for prevention and early treatment of RA.
Furthermore during year 4 of RTCure, detailed studies on immune processes responsible for the progression from asymptomatic autoimmunity to joint pain and bone loss were performed. Regulatory mechanisms at various phases of RA development were studied. To coordinate our efforts, a registry of individuals at risk for RA has been established. This registry is the first of its kind exploring early stages of RA and will be an important tool for recruitment of individuals in upcoming clinical trials.
Additionally, a regulatory expert team has been set up which during year 4 has completed a document which will be used to approach regulators with the aim to advance the development of EMA guidelines for the execution of clinical trials in a population at risk for RA. A first meeting between our task force in RTCure and the Swedish Medical Agency happened in May 2021, resulting in a positive feed-back from the agency and encouragement to continue interactions with regulators concerning advice and guidelines for clinical trials in the at risk for RA phase. We were advised to take this next step after results from the two most imminent clinical trials on RA prevention are publicly available. Interactions with Patient Research Partners have continued and been extended, so was the work with our Patient Research Partner coordinator lead, paid by RTCure for coordination of Patient Research Partners’ contributions to the goals of RTCure.
Some delays in several of the tasks have occurred due to the COVID-19 Pandemic and the closure of laboratories. Also the work with developing an At risk for RA registry in WP2 has been indirectly affected and delayed by the pandemic.
We are currently waiting for the first results from interventions with immunomodulatory drugs for prevention of RA, and expect major novel results both concerning clinical outcomes and concerning immunological mechanisms during the coming year.