Check lung function before prescribing methotrexate

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Rheumawire

Feb 4, 2004

Check lung function before prescribing methotrexate

Gateshead, UK - All patients being considered for methotrexate treatment

for rheumatoid arthritis (RA) should have lung-function tests, rather

the chest x-ray currently recommended, to weed out patients with lung

abnormalities such as fibrosis and so reduce the risk of the potentially

fatal and unpredictable side effect of MTX pneumonitis.

The proposal comes from 2 UK rheumatologists, Dr Videvelu Saravanan

(Freeman Hospital, Newcastle-upon-Tyne) and Dr CA (Queen

Hospital, Gateshead), writing in a Viewpoint article in the February

2004 issue of Rheumatology [1].

At present, guidelines on prescribing methotrexate in RA from both the

British Society of Rheumatology (BSR) and the American College of

Rheumatology recommend a chest x-ray before starting treatment. And it

seems that most physicians, at least in the UK, do follow this

recommendation, Saravanan comments; in a pilot survey he conducted at

the BSR meeting 2 years ago, 60% to 70% of rheumatologists said they did

so, he tells rheumawire in an interview.

" But the chest x-ray is an insensitive screening tool for lung disease, "

he says. " It shows up normal even in some patients who have lung disease

and pneumonitis. "

Instead, Saravanan and propose that new patients are screened with

lung-function tests. This is composed of 2 partstests on a simple

spirometer to measure forced expiratory value (FEV1) and vital capacity

(VC), which could be carried out by any physician, but also a transfer

factor for carbon monoxide (TLCO) test, which needs to be carried out on

specialist equipment found in a lung-function laboratory. There may be

some delay in sending the patient for these tests and obtaining the

results, perhaps 2 to 3 weeks in the UK, Saravanan says, but he says the

patient can be started on MTX immediately while waiting for the results.

The TLCO test assesses the transfer of oxygen from the lungs into the

blood and so gives an indication of how well the lungs are working. It

is more sensitive than a chest x-ray in identifying interstitial lung

disease or pneumonitis, he says.

A mild abnormality on the lung-function tests due to smoking is not a

contraindication for MTX, the researchers comment. Neither are abnormal

findings indicating chronic bronchitis or asthmain fact, in these cases,

methotrexate may even be beneficial for the lung disease as well as for

the rheumatoid arthritis for which it is being prescribed, Saravanan

tells rheumawire. However, a low value on the transfer tests is

suggestive of pulmonary fibrosis and " here we are in riskier territory,

where methotrexate may harm rather than help. "

Patients with a TLCO <70% of the predicted value should be sent for a

high-resolution computed tomography (HRCT) of the lungs, which has the

ability to distinguish between different lung diseases, the researchers

suggest. If HRCT confirms interstitial lung disease, MTX should be

avoided and an alternative disease-modifying antirheumatic drug (DMARD)

should be considered. Azathioprine, steroids, and cyclophosphamide have

all been used successfully in the treatment of interstitial lung disease

associated with RA, they note. However, if the HRCT shows only airway

disease, MTX can be used, and inhaled steroids can be added for patients

with symptomatic airway disease, they add.

Having baseline lung-function tests would help also help in a diagnosis

of MTX pneumonitis, which is often unclear at presentation. If an RA

patient on MTX presenting with acute respiratory symptoms has results on

lung-function tests that are the same as they were at baseline, " it's

almost 99% certain that the problem is not methotrexate pneumonitis, "

says Saravanan. This allows patients who are doing well on MTX to

continue with the therapy, he adds.

Commonly, patients on MTX complain of subjective breathlessness with no

obvious cause. Saravanan comments that he suspects that MTX pneumonitis

is more common than has been reported, as many RA patients on MTX are

not mobile enough to notice that they are becoming breathless. Without

baseline lung-function tests with which to compare repeat tests, it's

difficult to be sure there is no pneumonitis, he adds.

The reported incidence of MTX pneumonitis, a potentially fatal

hypersensitivity reaction, varies from 0.86% to 6.9% and is most

frequent in the first year of treatment. Pneumonitis is the reason for

MTX withdrawal in 1 in 108 patient-years, compared with 1 in 35

patient-years for hepatic toxicity and 1 in 58 patient-years for

neutropenia. However, pneumonitis is far less predictable than hepatic

and hematologic toxicity, the researchers comment. It's not unique to

MTX and has also been reported with sulfasalazine and gold treatment for

RA and has recently been reported with leflunomide (Arava®, Aventis).

Saravanan tells rheumawire that he has seen 1 patient on leflunomide

with pneumonitis but points out that many patients on leflunomide have

probably been taking MTX previously, and in some cases patients may be

taking the 2 drugs concomitantly.

Although screening with lung-function tests will add initially to the

costs of treating RA patients, these initial costs (around £100 in the

UK) should be offset later on by the " ability to confirm or refute MTX

pneumonitis more easily in the event of an acute respiratory illness, "

the researchers comment. In addition, it should decrease the risk of

this adverse effect by identifying patients most at risk of respiratory

failure from pneumonitis and avoiding MTX use in this group, they

conclude.

Zosia Chustecka

Source

1. Saravanan V, CA. Reducing the risk of methotrexate pneumonitis

in rheumatoid arthritis. Rheumatology (Oxford) 2004 Feb; 43(2):143-7.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org