DERBY, Great Britain—The latest British National Institute for Health and Clinical Excellence Technology Appraisal guidelines for use of TNFα inhibitors in rheumatoid arthritis (RA) make the baseline 28-joint Disease Activity Score (DAS28) the key metric that determines initial and ongoing access to these drugs for patients treated by National Health Service physicians.

The regulations require that patients must have a DAS28 of >5.1 on at least two occasions 1 month apart to become eligible for anti-TNF treatment. They further require that patients have a drop of ≥1.2 points on DAS28 within 6 months after beginning anti-TNF treatment and maintain that improvement on DAS28 every 6 months thereafter. Patients whose DAS28 comes within 1.2 points of their baseline DAS28 at any point are classified as nonresponders and lose access to TNF inhibitors.

“It would seem most appropriate to take the highest of the pre-assessment DAS28s, because that which is accepted as the baseline score makes a big difference whether or not a patient is subsequently classified as a nonresponder.”—Natalie Smith, MD
“This makes the baseline DAS28 of critical importance. If a patient has a baseline DAS28 that underrepresents their usual disease activity prior to anti-TNF therapy, this might increase the likelihood of subsequent assessments suggesting a loss of, or no response,” said lead author Natalie Smith, MD, from the department of rheumatology at Derbyshire Royal Infirmary in Great Britain.1

Dr. Smith and colleagues retrospectively analyzed outcomes in 256 patients according to the new criteria to determine whether the effect classified patients as responders or nonresponders. They also asked whether the common British practice of withholding steroids from RA patients during the period before the baseline DAS28 assessment to avoid a reduced DAS28 at baseline is really necessary or merely subjecting patients to 1 to 2 months of unnecessary misery.

“Comparing the differences in DAS28 from the first pre-assessment to baseline, the responders had increased by 0.4, and the nonresponders had decreased by 0.4 (P <.001). If the first pre-assessment score had been taken as the baseline DAS28, then 9.4% of the responders would be reclassified as nonresponders, and 31.8% of the nonresponders would be reclassified as responders,” Dr. Smith reported.

Steroid treatment (intramuscular, intra-arterial, or oral) had no significant effect on whether patients were classified as responders or nonresponders after 6 months of TNFα inhibitor treatment. The proportion of patients who were classified as nonresponders was 29% for adalimumab, 11% for etanercept, and 35% for infliximab (P <.001).

“[T]he DAS28 that is counted as the baseline is now more important than ever. It has become the reference value against which all the subsequent assessment of an individual patient’s response to anti-TNF is measured. Patients with lower baseline DAS28 are likely to get less of a drop in their DAS28. Although the majority of patients are classified as responders at 6 months according to the NICE guidelines, a significant proportion is not. Our retrospective study shows that the baseline DAS28 is critical to classifying responder and nonresponders at 6 month assessment,” Dr. Smith said. She noted that replacing the baseline score with the first pre-assessment DAS28 led to a significant reclassification of responders and nonresponders.

Translating research into practice

“Taken together, our data suggest that withholding symptom-relieving steroid therapy in the months prior to anti-TNF treatment does not increase the chances of being classified as nonresponders and there is no reason to deny steroids to patients around this pre-assessment period,” Dr. Smith concluded.

The investigators also suggested that pre-assessment taken 1 month apart?an interval not supported by any validated rationale?inappropriately delays access to anti-TNF therapy, because there were high correlations among pre-assessment scores and because patients with DAS28 >5.1 at the first pre-assessment rarely have a DAS28 below this at subsequent assessments.

“It would seem most appropriate to take the highest of the pre-assessment DAS28s, because that which is accepted as the baseline score makes a big difference whether or not a patient is subsequently classified as a nonresponder,” Dr. Smith said.

Reference
1. Smith N, Ding T, Butt S, et al. The importance of baseline Disease Activity Score 28 in determining responders and nonresponders to anti-TNF in UK clinical practice. [published online ahead of print July 4 2008]. Rheumatology. 2008. http://rheumatology.oxfordjournals.org/cgi/content/abstract/ken233v1.