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Comparing the effectiveness and safety of additional low-dose glucocorticoid in treatment strategies for elderly patients with rheumatoid arthritis

Periodic Reporting for period 4 - GLORIA (Comparing the effectiveness and safety of additional low-dose glucocorticoid in treatment strategies for elderly patients with rheumatoid arthritis)

Reporting period: 2019-03-01 to 2020-08-31

GLORIA aims to prove that the addition of chronic low dose glucocorticoids (GC) to current antirheumatic therapy is highly cost-effective and safe in elderly patients with rheumatoid arthritis (RA). The main component of GLORIA is a large pragmatic trial: 450 elderly (>65y) RA patients receiving standard of care will be randomized to additionally receive 5 mg prednisolone daily or placebo for 2 years. A novel tool will monitor compliance; it can send personalized reminders to a patient’s smart device. The efficacy of this technology will be tested in a nested trial. Compliance and other characteristics will be entered into a model that will allow personalized risk and benefit assessment in the future. Qualitative research in patients and physicians of member states will explore expectations and challenges in guideline implementation. This information and the study results will enable an update to existing guidelines and patient information, in collaboration with guideline committees and regulatory agencies. Networking conferences will improve health technology assessment in the elderly in general.
The fourth period of the project comprised ongoing data collection and the start of data review. Data collection was substantially affected by the covid crisis, forcing many centres to postpone or cancel in-person visits. These were replaced by telephone consultations, allowing data collection by questionnaire to continue. The amount of missing data (clinical, lab and imaging assessments) is currently being assessed as centres close with last patient last visit. We are currently updating our statistical analysis plan to optimize imputation. This will allow a valid assessment of the study endpoints.
Exploratory analysis (blinded) of baseline data reveals mean age of the included patients to be 73 (range 65-90), and moderate RA disease activity, indicating successful representation of the target population. Inadvertently entered data of one not-included patient was removed: final count of the total trial population is 451. Ongoing collection of the harm endpoint indicates 22% of the patients have experienced at least one serious adverse event, and additionally 40% of patients at least one (non-serious) event of special interest, for a total of 62% of patients. At this rate, the power of the study to detect a potential increase of harm in the prednisolone group has substantially increased despite the reduced sample size. With 80% power, we now can detect an increase in harm of 21%, compared to 38% in the original estimation.
The adherence sub-study has closed with a total of 38 patients. Of the EU countries participating, only a limited number of patients in the Netherlands possessed a smart device. (see WP 5).
In this period several posters were presented at scientific meetings, and manuscripts were published (open access) in peer review journals (see WP 8).
The protocol of the GLORIA TRIAL was published: Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial): study protocol for a randomized controlled trial.
Hartman L, Rasch LA, Klausch … Boers M.Trials. 2018 Jan 25;19(1):67. doi: 10.1186/s13063-017-2396-3.

Observations on the recruitment of patients to the GLORIA Trial were reported as a publication:
Remarkable international variability in reasons for ineligibility and non-participation in the GLORIA trial.
Hartman L, Bos R, Buttgereit F, … Boers M.Scand J Rheumatol. 2019 Jul;48(4):340-341.

Reports on different aspects of the trial were presented at International Conferences:
EULAR 2018: Outcome Measures for adherence data from a medication event monitoring system: A literature review.
Hartman L, Lems WF, Boers M

EULAR 2020: Medication adherence data in a randomized trial: large challenges to come from raw data to a workable and reliable dataset. Ann Rheum Dis 2020; 79 Suppl:A1873. Hartman L, Alessandri E, Bos R, …, Boers M.

EULAR 2020: In elderly patients, caps that record medication bottle openings are unreliable and thus not the gold standard for adherence. Ann Rheum Dis 2020; 79 Suppl:A894. Hartman L, Paolino S, Bos R, … Boers M.