Subsidised access to TNF-α inhibitors: is the rationale for exclusion of rheumatoid-factor-negative patients defensible?

To the Editor: Wyeth Australia welcomes the opportunity to comment on Lu and colleagues’ discussion of whether rheumatoid factor status is a predictor of tumour necrosis factor-α (TNFα)-inhibitor response in rheumatoid arthritis (RA).1 Wyeth provided the data used by the Pharmaceutical Benefits Advisory Committee (PBAC) to originally exclude patients who test negative for rheumatoid factor from access to TNF-α inhibitors. Although Wyeth agreed with the PBAC’s interpretation that only patients with positive rheumatoid factor status may benefit from etanercept, efficacy in those testing negative for rheumatoid factor was not clearly established because of the small number of patients in these subgroups.

Importantly, the subgroup analysis divided all study participants into two groups depending on their rheumatoid factor status and only included ACR 20 response (a standard from the American College of Rheumatology which requires at least 20% reduction in swollen joint count, tender joint count, and in three out of five of patient’s assessment of pain, patient’s assessment of disease activity, investigator’s assessment of disease activity, acute phase reactant levels and patient’s assessment of disability). This analysis may not represent the likely response of patients who test negative for rheumatoid factor, but who develop severe, progressive rheumatoid arthritis and otherwise meet the stringent eligibility criteria associated with Pharmaceutical Benefits Schedule listing (excluding positive rheumatoid factor status). It is possible that the small number of unique rheumatoid-factor-negative patients who have severe disease will not have a different response to etanercept from similar patients who are rheumatoid-factor positive.

More recent data are available from a large multicentre study that compared treatment with etanercept in combination with methotrexate to either monotherapy alone for control of RA disease activity.2 Subgroup analysis for the effect of rheumatoid factor on treatment responses showed that the presence of rheumatoid factor in the circulation of study patients did not significantly affect the responses to therapy among treatment groups. Although these new data have yet to be presented to the PBAC for reconsideration, a submission on this matter is under way.