TIME’S TEACHINGS

Rheumatic diseases affect the daily lives of millions of patients world-wide, resulting in a major economic and social burden, not only due to a decreased quality of life for patients, but also in lost productivity at work and increased health care costs for society. The main rheumatic diseases are rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and Osteoarthritis (OA). Cohorts at Reade Most rheumatic diseases are chronic in nature, progressing over time. And, as rheumatic diseases are as yet managed, not cured, patients must receive ongoing care and treatment for their chronic condition. Patients visit the rheumatologist’s office for years, if not decades of drug and other treatments. This makes monitoring of long-term outcomes especially important to consider, as the effects of any (drug) treatments may have a long-term impact on patients’ functioning. At Reade, we have two long-term cohorts to ensure long-term follow-up with consistent assessment of key criteria for disease severity and patient reported outcome measures (PROMs). The goal of these cohorts is to monitor efficacy in daily clinical practice, as this can differ from the clinical (registration) trials, e.g. due to different patient selection. The Reade Rheumatology Registry is an observational daily clinical practice inception cohort that was initiated to capture long-term data on patients using biologicals and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) in inflammatory rheumatic diseases, started in 2004 and comprises RA, PsA and AS patients starting on a new b/tsDMARDs therapy. In the Amsterdam Osteoarthritis (AMS-OA) cohort, started in 2009, consecutive patients presenting to the clinic with knee or hip OA were enrolled regardless of medication use. In this cohort activity limitations and cardiovascular disease (CVD) and its risk factors were assessed. In the following sections a brief summary will be given of the studies in this thesis and their main results. Unless otherwise noted, the cohort used is the Reade Rheumatology Registry. SECTION 1: EFFICACY AND DRUG SURVIVAL IN COHORTS This thesis comprises two sections: Section 1 focussed on the efficacy and drug survival in cohorts, the primary reason the cohorts were started. Within section 1, Chapter 2 evaluated the influence of the trial inclusion criteria used (with adalimumab for RA) on clinical outcome and response. We observed that the inclusion criteria can have a marked effect on the expected response, i.e., improvement from baseline is much greater in trials with strict inclusion criteria (and worse disease activity at baseline). However, contrary to expectation, final disease activity appeared much less dependent on initial disease activity. In Chapter 3 we examined the changes in the initial DAS28 response during the first 6 months related to changes in patient and disease characteristics in patients starting bDMARDs or tsDMARDs between 2004 and 2020. Subsequently, in chapter 4 we examined the changes in drug survival over a period of 15 years (2004-2019), to study whether drug survival was different for patients with RA, PsA and AS starting TNFi in recent years versus those who started shortly after the drugs were introduced. SECTION 2: COMORBIDITIES AND NON- RHEUMATOLOGICAL DATA COLLECTED WITHIN COHORTS While Section 1 focussed on safety and efficacy of treatment, Section 2 analyzed comorbidities and non-rheumatological data collected in the cohorts. By collecting a wide variety of data over more than 15 years, we were able to investigate multiple comorbidities, each adding to the burden and medical complications in the patients’ lives. We examined cardiovascular diseases (CVD), renal function and uveitis. In addition, we also studied gender differences within the Reade Registry.