When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.
Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.
The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).
Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.
In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.
The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.
Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).
"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).
To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.
"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.
Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.
However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.
Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).
Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.
"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.
Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.