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We have with great interest read the letter by Mäkinen, Hannonen and Sokka in the July issue of the ARD, 2008 (1). The authors make the point that the sex differences in remission rates assessed by DAS28 in patients with early RA reported by us (2,3) may be spurious due to the fact that DAS 28 does not take into account gender differences in erythrocyte sedimentation rate (ESR). Consequently they propose tha...
We have with great interest read the letter by Mäkinen, Hannonen and Sokka in the July issue of the ARD, 2008 (1). The authors make the point that the sex differences in remission rates assessed by DAS28 in patients with early RA reported by us (2,3) may be spurious due to the fact that DAS 28 does not take into account gender differences in erythrocyte sedimentation rate (ESR). Consequently they propose that we calculate ACR remission rates from our data to see whether the sex differences found by DAS28 will remain or disappear. However, we already addressed this question in our study (3). We quote from the results section:
“To investigate whether the sex difference in remission rate would also be evident in the presence of more stringent criteria, the clinical criteria described by Mäkinen et al. were applied. (4).” “By these criteria, remission at 2 years was achieved by 17.8% of the women and 26.8% of the men (p=0.005), remission by 5 years by 21% of the women and 28.5% of the men (p=0.039) and remission achieved both at 2 and 5 years by 9.5% of women and 16.4% of men (p=0.013). Thus, by these stringent
remission criteria, overall remission rates were considerably lower than those by the DAS28 criterion, but the significant sex difference remained.”
Admittedly, these clinical criteria are not equal to the ACR criteria (5), but they do take the gender differences in ESR into account.
However, the ACR criteria were not applied in our study (3). Therefore we have reviewed our data. 552 of the 698 patients had values for all variables included in the ACR criteria (no swollen, no tender joint, painVAS ≤10 mm, morning stiffness ≤ 15 min, ESR ≤30 mm in women and ≤ 20 mm in men, fatigue excluded). The results show that 10.4% of the women and 16.2% of the men met all five criteria at 5 years, p=0.048. Thus, our data show gender differences in remission rates also when strict criteria are applied and when gender differences in ESR are accounted for.
These data lead to some considerations. Looking at the individual patients, it becomes evident that unacceptably many patients are erroneously classified as non-remitters by the ACR criteria. E.g., the presence of a single tender joint in association with no swollen joint, normal ESR, morning stiffness 5 minutes and pain VAS 5 mm would hardly be regarded as evidence of ongoing active disease. Several more plausible explanations to a single tender joint would instead be considered.
Likewise, an ESR of 36 mm in a woman without swollen and tender joints, morning stiffness and pain (VAS 2 mm) would rather be assigned to some other cause than active RA. Furthermore, classifying a patient with only a pain VAS of 13 mm or only a morning stiffness of 30 minutes in absence of other criteria does not seem to warrant a judgment of no remission. Such patients were numerous enough in our study to question the clinical relevance of the ACR criteria.
1. Mäkinen H, Hannonen P, Sokka T. Sex: a major predictor of remission as measured by 28-joint disease activity score (DAS28) in early rheumatoid arthritis? Ann Rheum Dis 2008;67:1052-3.
2. Tengstrand B, Ahlmén M, Hafström I, for the BARFOT Study Group. The influence of sex on rheumatoid arthritis: A prospective study of onset and outcome after 2 years. J Rheumatol 2004;31:214-22.
3. Forslind K, Hafström I, Ahlmén M, Svensson B for the BARFOT Study Group. Sex: a major predictor of remission in early rheumatoid arthritis? Ann Rheum Dis 2007;66:46-52.
4. Makinen H, Kautiainen H, Hannonen P, Sokka T. Frequency of remissions in early rheumatoid arthritis defined by 3 sets of criteria. A 5-year followup study. J Rheumatol 2005;32:796-800.
5. Pinals RS, Masi AT, Larsen RA, and the subcommittee for criteria of remission in rheumatoid arthritis of the American Rheumatism Association diagnostic and therapeutic criteria committee. Preliminary criteria for clinical remission in rheumatoid arthritis. Arthritis Rheum