effectiveness of treating to the target of remission strategies in patients with early rheumatoid arthritis
Laura Steunebrink is a PhD student in the Department of Psychology, Health & Technology. Her supervisor is prof.dr. M.A.F.J. van de Laar from the Faculty of Behavioural, Management and Social sciences (BMS).
Rheumatoid arthritis (RA) is an inflammatory disease of the connective tissues of the body, particularly the synovial joints. Persistent inflammation may lead to damage of the joint capsule and the articular cartilage. Several clinical trials and studies in daily clinical practice have shown that early, aggressive suppression of inflammation leading to sustained remission or at least a state of low disease activity can prevent or minimize joint damage and associated disability. Current treatment guidelines advocate treat-to-target (T2T) as the optimal treatment approach [1]. Within this treatment paradigm, successive medication adjustments are made until a predefined disease activity target (usually remission or low disease activity) is reached. Accumulating evidence suggests that a T2T approach leads to better clinical outcomes than alternative treatment approaches, but it is still unclear whether T2T can be further optimized. The main objective of this thesis was to compare and explore the effects of a step-up DMARD monotherapy versus an initial DMARD combination therapy according to a T2T strategy aiming at remission in early RA. For this, the Dutch RhEumatoid Arthritis Monitoring (DREAM) collaboration started two T2T remission induction cohorts, both with different medication protocols, the results of which were presented in this thesis.
SUMMARY AND MAIN FINDINGS
Chapter 3
This chapter presented remission rates and predictors of remission in a real-life T2T cohort (initial DMARD combination therapy) of consecutive patients with a recent clinical diagnosis of RA. Remission was achieved rapidly in almost 80% of recently diagnosed RA-patients during the first year of their disease. Among a wide range of possible prognostic factors for achieving remission, no accurate predictors could be identified. This provides additional evidence that a T2T strategy aiming at remission is universally beneficial for recently diagnosed RA patients in clinical practice and can therefore be implemented widely. The vast majority of the patients in the current study achieved the treatment target using csDMARDs only and only 10% of patients needed treatment with bDMARDs within the first 12 months. This study confirmed that remission is a realistic goal in daily clinical practice. Moreover, the current T2T strategy appears to be broadly applicable to all patients with recently diagnosed RA. Together with the absence of clear baseline predictors, this suggests that clinicians aiming at remission in daily clinical practice may focus on outcomes only, without needing to take other patients characteristics into account.
Chapter 4
This chapter aimed to compare the effectiveness of two T2T strategies in early RA patients. For this purpose, a step-up approach starting with methotrexate (MTX) monotherapy (strategy I) was compared to an initial DMARD combination approach (strategy II). The results of this study suggest that the previously reported outcomes that were achieved by implementation of T2T with initial MTX monotherapy in daily clinical practice may be reproduced, and even improved upon, using an initial DMARD combination approach. Initial DMARD combination therapy resulted in comparable remission rates after one year but a significantly shorter median time to remission. At 6 months, mean disease activity scores were lower in patients with initial DMARD combination treatment than in those with DMARD step-up therapy. At 12 months, no significant differences remained in mean DAS28 scores or the proportion of patients in remission. In conclusion, T2T using initial combination therapy leads to a significantly shorter time to achieve first remission.
Chapter 5
This chapter compared the radiographic outcomes of step-up DMARD monotherapy (strategy I) versus initial DMARD combination therapy (strategy II). This study showed that patients with initial DMARD monotherapy had significantly more, and more frequently clinically relevant, radiographic progression after one year. A substantially larger number of patients within strategy II showed no radiographic progression at all and only a small portion of patients showed clinically relevant progression. For clinically relevant progression, fewer tender joints and higher ESR were significantly associated with reaching a MCID.
Chapter 6
This chapter explored the association between achieving favorable clinical outcomes and patients’ perceived changes in overall health status after 12 months of T2T in patients with early rheumatoid arthritis and aimed to identify determinants of subjective non-improvement. Results showed that more than one-third of the patients (35%) did not consider their overall health to have improved, despite having achieved favorable clinical outcomes. Relative change from baseline in VAS pain and VAS fatigue was independently associated with non-improved perceived overall health status. This study showed that clinical improvements do not equate with improved subjective health for all patients. Improvement in clinical signs and symptoms alone may not be enough to achieve favorable health outcomes for all early RA patients. Therefore, the association of non-improvement with changes in pain and fatigue suggests that it might be worthwhile to monitor and address pain and fatigue in addition to and independently of disease activity in early rheumatoid arthritis.
Chapter 7
This study examined the longitudinal relationship between disease activity and radiographic progression in patients with early rheumatoid arthritis in the current era of intensive treat-to-target (T2T) in daily clinical practice. At the group level, no significant correlations between time-integrated disease activity and radiographic progression were observed at the 6 month and 2-year follow-up. At 1-year and 3-year follow-up there was only a very weak positive association. A wide inter-individual variation between disease activity and radiographic progression was also apparent from the individual trajectory plots. However, the slopes of the individual lines in each time interval confirmed a fairly proportional relationship between disease activity and radiographic progression within patients. Especially the slopes in the first 6 months were strongly related to the slopes in the later time points. In 12 – 30% of the patient in time-integrated remission, relevant radiographic damage (SHS ≥ 3) continued. These findings suggest that, in the era of T2T, radiographic damage is no longer caused by only (consistent) high disease activity, but is primarily an individually determined disease process.
