Rheumatoid Arthritis Viewpoint-Current Edition from Veritas Medicine

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I'm not sure if the other was a bad link, but here is the article:

Lymphoma in RA Patients Treated With Methotrexate

06/28/2002

Methotrexate is currently the most commonly prescribed disease modifying

drug for the treatment of RA.  Clinical experience with weekly methotrexate

for RA is extensive, dating back over 20 years.  The most common toxicities

associated with weekly methotrexate are gastrointestinal, including nausea,

vomiting and diarrhea.  However, other systems can be affected by

methotrexate, including the liver, the lungs and then blood-forming tissues

in the bone marrow. 

 

Reports also exist of rare side effects whose true association with

methotrexate use remains unknown.  One of these associations is the

development of the blood cell cancer, lymphoma.  There have been several

reported cases of lymphoma in patients receiving methotrexate, including

some cases which resolved when methotrexate was discontinued.  However, the

association remains unclear.  One study that reviewed over 16,000 patients

treated with methotrexate did not identify an increased risk of lymphoma. 

The association between lymphoma and methotrexate is particularly

complicated by the fact that people with RA are already at an increased risk

for developing lymphoma, even in the absence of methotrexate therapy.

 

To further address the risk of developing lymphoma due to methotrexate

therapy, a group of French investigators recently studied a large group of

patients with RA to define the risk of developing this disease while on

methotrexate therapy.  Sixty-one French rheumatology centers identified all

RA patients treated with methotrexate who developed lymphoma in the years

1996 to 1998.  The total number of patients in France with RA taking

methotrexate was estimated by population statistics at between 27,000 and

30,000.

 

During this three-year period, 25 new cases of lymphoma were documented.  Of

these cases, 18 were non-Hodgkin¹s lymphoma (NHL) and 7 were Hodgkin¹s

disease (HD).  Many of these patients had longstanding RA disease with

evidence of joint destruction.  In all 25 patients who developed lymphoma,

methotrexate was withdrawn.  Three of these patients achieved an initial

spontaneous remission; however, the remission was sustained in only one

patient with the non-Hodgkin's form of lymphoma. 

 

Upon comparing the frequency of development of these two types of lymphoma

between RA patients in general and the French population in general, there

was no apparent increased risk for developing non-Hodgkin¹s lymphoma.  In

contrast, the development of Hodgkin¹s disease was significantly higher in

RA patients taking methotrexate than in the general population. 

 

From these results, the investigators point out this is the first study

suggesting an increased risk of lymphoma, in particular the Hodgkin¹s

disease type, in RA patients treated with methotrexate.  Since they noted

spontaneous remission in a small number of patients, they also suggest

delaying chemotherapy for appropriate patients, to allow for the possibility

of spontaneous improvement when methotrexate is stopped.  But they caution

that even in the event of spontaneous improvement, close monitoring remains

mandatory because the disease reoccurred for some patients. 

 

One shortcoming noted by the investigators that was not quantified in this

study is the development of lymphoma in RA patients not receiving

methotrexate.  Thus, the issue of whether the increase in lymphoma detected

in this study relative to the general population results from methotrexate

therapy or from the disease process of RA itself remains an open question. 

Overall, however, this study provides patients and physicians with valuable

information about the risk of developing lymphoma, and should lead to a

heightened awareness about this possible complication in RA patients. 

 

1  Mariette, X., et al.  ³Lymphomas in rheumatoid arthritis patients treated

with methotrexate:  a 3-year prospective study in France.²  2002.  Blood

99(11):3909.

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