NEW YORK (Reuters Health)—Certain rheumatoid arthritis (RA) patients doing well on etanercept and methotrexate may be able to quit the latter agent if they have tolerability problems, according to an open-label Canadian study.
In a Sept. 11 online paper in Rheumatology, Dr. Boulos Haraoui, of the University of Montreal, and colleagues noted that although combination therapy has been shown to lead to improved clinical outcomes, clinicians or their patients may wish to discontinue methotrexate.
To investigate further, the researchers examined data from a study in which patients with inadequate response to methotrexate received etanercept plus methotrexate for six months. They were then randomized to either etanercept monotherapy or continued etanercept plus methotrexate for an additional 18 months.
At month 24, the mean increase from baseline to month 24 in the modified total Sharp score (mTSS) was 0.4 in the 98 etanercept monotherapy patients, with no change in the 107 combination patients. There was also no increase in joint space narrowing or erosion in the combination group.
At month 24, the corresponding mean increase from month six in mean scores/count increases for 28-joint disease activity score (DAS28) with ethrocyte sedimentation rate (ESR) were 0.56 and 0.08. For Simplified Disease Activity Index, these were 4.7 and 0.9. Other outcome measures also favored the combination group.
Patients with DAS28-ESR low disease activity (LDA)/remission at month six had numerically better outcomes at month 24 than patients with moderate to high disease activity at month six.
In fact, in patients with LDA or remission at six months, outcomes at 24 months were similar between groups, suggesting that methotrexate could be withdrawn should there be problems with tolerability, side effects, or compliance.
As Dr Haraoui told Reuters Health by email, “Patients, who achieve at least LDA (based on DAS28) after adding etanercept to standard doses of methotrexate, may eventually stop their methotrexate and maintain their clinical response without any deleterious effect on structural damage progression.”
This observation, he added, “helps guide clinicians in their discussion with patients who wish to stop methotrexate when taken in combination with etanercept.”
Rheumatologist Dr. Clive A. Kelly, of Queen Elizabeth Hospital, Gateshead, UK, who has conducted research in the field, told Reuters Health by email, “In those who remit within six months of commencing biologic therapy with etanercept and methotrexate support, it may be possible to withdraw methotrexate at this stage without loss of disease control, although this may not be necessary if the patient has no contraindications to its continuation, as this study showed no increased in adverse events as a result of the combination.”
He concluded, “Those patients with persistent disease activity after six months of therapy need to continue both biologic and methotrexate therapy in combination for at least two years to optimize the response to treatment. It is unclear from this study whether subsequent cessation of methotrexate can be considered.”
In North America, etanercept (Enbrel) is co-marketed by Amgen and Pfizer. The study was supported by Amgen Canada and Pfizer Canada. Dr. Haraoui has received support from Amgen and Pfizer. Other authors also have relationships with these companies and one is currently an employee of Amgen.
