Only about 10% of rheumatoid arthritis patients reach remission after a year on TNF-alpha inhibitors. Is this a problem with the regimen, the definition of remission, or the focus of the treatment target?
Balogh E, Dias JM, Orr C, et al., Comparison of remission criteria in a tumour necrosis factor inhibitor treated rheumatoid arthritis longitudinal cohort: patient global health is a confounder.Arthritis Research & Therapy (2013) 15:R221 doi:10.1186/ar4421
To judge by new remission criteria set by the American College of Rheumatology (ACR) or European League against Rheumatism (EULAR), only a small percentage of rheumatoid arthritis (RA) patients reach remission after up to a year on tumor necrosis factor-alpha (TNFÎ±) drugs. This is the result of a new analysis by Irish researchers.
According to their study, the strongest predictor of non-remission was low patient global health (PGH) assessment at baseline. They describe PGH as a "confounder," but it raises fundamental questions about the nature of remission.
Looking to assess the frequency and sustainability of remission, the study assessed treatment responses among 273 biologic-naÃ¯ve patients at an RA clinic in Dublin. It calculated remission rates based on the ACR/EULAR criteria and on disease activity in 28 joints (DAS28) using either CRP or erythrocyte sediment rate (ESR) levels.
Only 10% of patients, the majority women in their 50s with mean disease duration of 13 years, met both ACR/EULAR and DAS28 criteria for remission at one year. Judging by the DAS28 criteria alone, 37% achieved remission.
The ACR/EULAR criteria define remission by lower disease activity than DAS28, so fewer patients will qualify. But those in the study who did “were better responders on a group basis than DAS28 remission patients,” the authors write.
RA patients who reached remission by ACR/EULAR criteria tended to be younger, to have lower tender joint counts, and to score better at baseline for both PGH and Disease Activity Score (DAS)28(4v) C-reactive protein (CRP).
Among the study group, at a year after starting starting TNFÎ± inhibitors 224 patients had met the EULAR criteria for good (50.5%) or moderate (31.9%) treatment responses, and 127 (17.6%) had not.
The authors of the current study suggest that because the new ACR/EULAR criteria “are more stringent in defining remission…they may lead to better long term radiographic outcomes” compared with the DAS28 criteria. But treatment response scales don’t tell the whole story about what constitutes true remission.
TNFÎ± inhibitors dampen inflammation and reduce disease activity, but do not treat pain and reduced function -- two factors assessed by PGH scores and remediated by other treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs).
One of the criteria in the ACR20 improvement scale (20% improvement in 3 of 5 areas) is patient pain assessment. Studies show that pain is the most important determinant of patient-ranked global assessments, while the physician’s global assessment (PGA) is influenced more by swollen joint counts. In another recent study, more than a third of patients reported worse global health than their rheumatologists perceived, due to greater pain and fatigue.
Could it be that patients who have low PGH scores to begin with are less likely to reach remission after a year on TNFÎ± drugs because of continued pain?
The authors did not address this question directly.