Clinical Deep Remission and Related Factors in a Large Cohort of Patients with Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, pain, and eventual joint destruction, leading to significant disability and impaired quality of life. Over the past two decades, advancements in the treatment of RA, particularly the early initiation of disease-modifying anti-rheumatic drugs (DMARDs) and the use of biologic DMARDs (bDMARDs), have revolutionized patient outcomes. Achieving clinical remission has become the primary treatment goal, as it is associated with better long-term outcomes and reduced disability. However, the definition of remission in RA remains a topic of debate, with various criteria used in clinical practice. This study aimed to investigate the prevalence of clinical remission in a large cohort of RA patients and to identify factors associated with achieving remission, particularly focusing on the role of sustained intensive DMARD treatment.
The study included 342 patients with RA who were recruited from three teaching hospitals in China between September 2015 and May 2016. The patients were clinically assessed by rheumatologists, and data were collected through face-to-face interviews and a four-page questionnaire. The study evaluated remission rates based on seven different criteria: Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), Routine Assessment of Patient Index Data 3 (RAPID-3), Boolean criteria, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and a newly described Clinical Deep Remission (CliDR) criteria. CliDR was defined as having no swollen or tender joints with normal ESR and CRP levels. The practicability of these criteria was rated by a panel of 42 rheumatologists.
The demographic characteristics of the cohort revealed that 74.3% of the patients were female, with a mean age of 54.5 years and a median disease duration of 70.5 months. Nearly half of the patients (45.3%) were smokers, and 5.9% had a positive family history of RA. The majority of patients were positive for anti-cyclic citrullinated peptide (anti-CCP) (76.0%) and rheumatoid factor (RF) (64.0%). The median Multidimensional Health Assessment Questionnaire (MDHAQ) score was 0.1, indicating relatively low functional disability in the cohort.
The remission rates varied significantly depending on the criteria used. The highest remission rate was observed with DAS28-CRP (38.0%), followed by DAS28-ESR (29.5%), RAPID-3 (24.9%), Boolean criteria (21.1%), SDAI (19.0%), CDAI (18.1%), and CliDR (17.0%). The Boolean and CliDR criteria were rated as the most practical by rheumatologists, with scores of 7.5 and 8.0, respectively. These findings suggest that while DAS28-CRP and DAS28-ESR may overestimate remission rates, Boolean and CliDR criteria provide a more stringent assessment of disease activity, reflecting true remission more accurately.
The study also examined the impact of treatment on remission. All patients who achieved remission were on DMARD therapy, and the median duration of DMARD treatment was significantly longer in the remission group (45.0 months) compared to the non-remission group (30.0 months). The most commonly prescribed conventional synthetic DMARDs (csDMARDs) were leflunomide (66.7%), methotrexate (59.7%), and hydroxychloroquine (46.8%). However, none of these csDMARDs was more frequently used in the remission group. Instead, combination therapy with two or more DMARDs was significantly associated with higher remission rates, with 75.9% of remission patients receiving combination therapy compared to 57.8% in the non-remission group.
Sustained intensive DMARD treatment, defined as combination therapy with two or more DMARDs for at least six months, was found to be a critical factor in achieving remission. Patients who received sustained intensive DMARD treatment had higher remission rates across all criteria, particularly with Boolean (25.6%), SDAI (23.8%), and CliDR (21.3%) criteria. These patients also had longer disease and treatment durations compared to those who did not receive sustained intensive treatment. The proportions of methotrexate, leflunomide, and hydroxychloroquine use were significantly higher in the sustained intensive treatment group, further emphasizing the importance of combination therapy in achieving remission.
The study also highlighted the limitations of current remission criteria, particularly the role of patient global assessment (PtGA) in Boolean and SDAI criteria. PtGA is a subjective measure that can be influenced by non-inflammatory factors such as osteoarthritis or fibromyalgia, leading to discrepancies in remission assessment. In contrast, CliDR, which relies on objective measures such as joint counts and laboratory markers, provides a more feasible and accurate definition of remission in clinical practice.
In conclusion, this study demonstrates that clinical deep remission is achievable in patients with RA, particularly with sustained intensive DMARD treatment. The findings underscore the importance of combination therapy and longer treatment durations in achieving remission. The CliDR criteria, which focus on objective measures of disease activity, offer a practical and stringent definition of remission that can guide treatment decisions in daily practice. Future studies should further validate the CliDR criteria and explore its long-term impact on radiographic progression and patient outcomes.
doi.org/10.1097/CM9.0000000000000227
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