RESEARCH - Second try with MTX may work in RA

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Second try with methotrexate may work in RA

Rheumawire

Mar 3, 2006

Gandey

Vienna, Austria - Patients with rheumatoid arthritis (RA) who had inadequate

response to a first course of methotrexate but have not had major toxicity

may be good candidates for a second round of methotrexate, perhaps at a

higher dose [1]. Reintroducing a prior therapy may represent a viable new

option for patients whose disease is not brought under adequate control

within a few months of treatment and for whom there are limited other

alternatives. These are the findings of a new study published online

February 24, 2006 in Arthritis Research and Therapy.

Senior author Dr Aletaha (National Institutes of Health, Bethesda,

MD) said that this approach does not necessarily require increasing the

methotrexate dose. " The effect of reemployment was also seen in many

patients in whom the doses were actually lower than in the original course, "

he told rheumawire.

" This therapeutic option may be valuable in patients in whom other

therapies-especially biologicals-cannot be used or have proven

insufficiently effective, " his group contends in their paper. " The results

of this investigation constitute an expansion of therapeutic strategies in

the care for RA patients. "

Many patients experience adverse events or continue to have active disease

despite intensive disease-modifying antirheumatic-drug (DMARD) therapy.

Consequently, DMARDs must be discontinued in the majority of patients within

three to five years, the researchers note. Changes to therapeutic regimens

are therefore frequently required during the chronic course of RA.

The investigators, led by Dr Theresa Karla (Medical University of Vienna,

Austria), looked at more than 1400 patients with RA. Patients were followed

from first presentation and yielded more than 6400 patient-years of

observation. The researchers identified patients who were prescribed a

second course of methotrexate-the most commonly used DMARD in clinical

practice-after at least one intermittent course of a different DMARD.

The team compared reasons for discontinuation, improvement in acute-phase

reactants, and cumulative retention rates of methotrexate therapy between

the original course and reemployment. They conducted similar analyses for

other DMARDs.

Second-use MTX success more likely if original dose was low

They found that methotrexate was reintroduced in 86 patients. Compared with

the original courses, a second prescription was associated with a reduced

risk for treatment termination due to inefficacy (p=0.02 by McNemar test).

The investigators found that this was especially true in instances where the

maximum dose of methotrexate had initially been low. The researchers did not

observe a similar effect in retreatment with other DMARDs.

" We were surprised by the fact that reemployment was successful in such a

large proportion of patients, " Aletaha told rheumawire. " Also, it was

intriguing that the dose of the original course was clearly determining the

success of the reemployed course-even if the reemployed dose was lower. "

The researchers observed that if patients had originally been treated with

10 mg per week or less, reemployment was ineffective in only about one third

of patients. If they had been treated with a dose greater than 17.5 mg a

week in the original course, the frequency of ineffectiveness on retreatment

was 75%.

They report that the effect of the original methotrexate dose on

effectiveness of reemployed courses was statistically significant (p=0.02

using logistic regression). They observed the same effect in subgroups of

patients whose reemployed methotrexate dose was higher than the original

dose and for those whose dose was lower or equal on reemployment.

The main limitation of the study is its observational design and its likely

bias by indication. But the researchers say there is no way a randomized

controlled trial would be feasible to address a similar question. They say

this observational design is therefore the best possible option.

" Of interest, " they add, " approximately 33% of patients on their first

methotrexate courses were still on the drug at the time of data extraction

for the study, which is a further indication of the significant

effectiveness of this DMARD in the treatment of RA. "

They conclude, " Given our present and previous findings on the role of

methotrexate dosing in these patients, it seems that an increase in

methotrexate dose should accompany any reemployment of methotrexate, but

that a previously unsuccessful course of methotrexate is not necessarily a

bad prognostic marker for ineffectiveness of renewed methotrexate treatment

at a later stage. "

Source

1. Karla T, Stamm T, Machold KP, et al. Methotrexate in

rheumatoid arthritis is frequently effective, even if reemployed after a

previous failure. Arthritis Res Ther 2006: 8:R46. Available at:

http://arthritis-research.com/content/8/2/R46.

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