Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, Clinical remission, Drug-free, Drug-tapering, csDMARDs, Synovitis
Brief summary
HARMONICS is a prospective registry embedded in the routine clinical practice of the Early Arthritis Clinic and the Prospective Remission Clinic at Fondazione IRCCS Policlinico San Matteo, with an associated research biorepository of voluntarily donated biological samples. It is designed to collect and generate long-term longitudinal data from patients with early-treated rheumatoid arthritis (RA) who have achieved stable clinical remission with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and undergo treatment tapering or discontinuation according to local care pathways, following shared decision-making between the patient and the treating rheumatologist. Following enrollment in stable clinical remission, patients are monitored as part of standard of care at regular intervals using clinical, ultrasound, and radiographic assessments to evaluate disease activity and outcomes. Treatment modifications, including tapering, discontinuation, and re-treatment, are recorded longitudinally. Participants are followed in the registry from enrollment for up to 60 months, unless a disease flare occurs earlier. Patients experiencing a disease flare within the initial 60-month follow-up period undergo an additional 12 months of follow-up after flare. The registry aims to provide a comprehensive longitudinal framework of multimodal data to advance the clinical and pathophysiological understanding of remission phenotypes and natural disease trajectories, with the ultimate goals of: * optimizing risk stratification and therapeutic decision-making in patients with RA in remission; and * identifying and exploring novel targets for potential transformative therapies.
Interventions
None listed
Sponsors
Fondazione IRCCS Policlinico San Matteo di Pavia
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Diagnosis of RA fulfilling the ACR/EULAR 2010 or ACR 1987 classification criteria within 12 months of first evaluation at the Early Arthritis Clinic * Initiation of csDMARD therapy within 12 months of symptom onset * Continuous treatment with csDMARDs for ≥24 months * No prior or current treatment with biologic or targeted synthetic DMARDs * DAS28-ESR \<2.6 for ≥6 months in the absence of glucocorticoid therapy * Management with a treatment tapering or discontinuation strategy with planned monitoring as part of routine clinical care, following shared decision-making with the treating rheumatologist * Ability to provide written informed consent for participation in the registry
Exclusion criteria
* Extra-articular manifestations of RA * Concomitant chronic inflammatory or autoimmune rheumatic diseases other than RA * Personal history of cutaneous and/or nail psoriasis * Severe cardiovascular disease * Severe functional disability impairing clinical protocol adherence or follow-up * Severe cognitive impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal disease control | From enrollment to 24 months of follow-up | Proportion of participants maintaining longitudinal disease control at 24 months of follow-up, defined as the combined fulfillment of: * absence of clinician-assessed rheumatoid arthritis flare over the 24-month follow-up period; * average annual change in modified Sharp/van der Heijde erosion score (ΔSHSe/year) ≤0.5; and * preserved functional status, defined as HAQ-DI \<0.5 at 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-flare of rheumatoid arthritis activity | From enrollment up to 60 months of follow-up. | Predictors of time-to-flare of rheumatoid arthritis activity over up to 60 months of follow-up, including: i) clinical variables, such as clinimetric indices, objective clinical parameters, and patient-reported outcomes; ii) ultrasound-derived variables, such as grey-scale synovitis scores and power Doppler scores; and iii) biological variables, such as phenotypic, molecular, and serological biomarkers. |
| Longitudinal changes in clinical, ultrasound-derived, and biological variables | From enrollment up to 24 months of follow-up | Characterization of baseline differences and absolute and relative longitudinal changes in clinical, ultrasound-derived, and biological variables in participants experiencing flare during follow-up (measured from enrollment to flare) and in participants remaining flare-free (measured from enrollment to matched follow-up time points aligned with flare occurrence). |
| Clinical and ultrasound response following treatment escalation or re-treatment due to arthritis flare | At 6 and 12 months after treatment escalation or re-treatment | Proportion of participants achieving clinical and ultrasound measures comparable to enrollment values at 6 and 12 months following clinically indicated treatment escalation or re-treatment due to arthritis flare. |
| Comorbidity burden during follow-up | From enrollment up to 60 months of follow-up. | Longitudinal changes in comorbidity burden (including cardiovascular, metabolic, infectious, neoplastic, and osteoporotic conditions), assessed by the occurrence of newly diagnosed comorbidities and/or changes in standardized comorbidity indices during follow-up. |
Countries
Italy
Contacts
CONTACTAntonio Manzo, MD PhD
PRINCIPAL_INVESTIGATORAntonio Manzo, MD PhD
University of Pavia/Fondazione IRCCS Policlinico San Matteo
Outcome results
None listed