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Improved methotrexate patient information.

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874
LETTERS
an association between HVR3, rheumatoid arthritis, persistent disease, and development of erosions does exist, markers such as R F and ACR criteria might still be more sensitive
and specific in delineating patients who have a greater
chance of developing severe disease, compared with DNA
oligotyping for the presence of HVR3. However, perhaps
the repeatedly demonstrated strong association of DR4
homozygosity with severe disease will turn out to be the
useful predictive parameter clinicians have been waiting for.
D. ILilic, MD, MSc, PhD
Mia'dlesbrough General Hospital
J . N. Fordham, MD, FRCP
South Cleveland Hospital
Mia'dlesbrough, UK
Reply
To the Editor:
Drs. Lilic and Fordhiam question whether HLA
typing has any role in predicting severity of disease outcome
in patients with symmetric polyarthritis. The ACR criteria
are indeed useful for predicting persistent disease, but these
criteria have low specificity for erosions (62%). In fact, since
the presence of erosions is itself one of the ACR criteria, it
is statistically inappropriate to use them for this purpose. In
practice, the important question in patients with persistent
synovitis is, how bad is the disease going to get? We looked
for predictive factors for erosions in patients who fulJilled
the ACR criteria; this is the rearson the ACR criteria were not
included in the analysis. Under these circumstances the
presence of the conserved HVR3 or R F proved to be very
helpful for making predictions with either high sensitivity or
high specificity. This is important when considering the
usual dichotomy between eacacy and toxicity in treating
rheumatoid arthritis. A safe but probably less effective
therapy needs a test with high sensitivity; patients with
either HVR3 or R F would be suitable for treatment with
such a drug. In contrast, a toxic but remittive regimen
requires tests with high specificity for severe erosive disease, such as that provided by the possession of both R F and
HVR3.
We were very surprised by Lilic and Fordham's
assertion that the strong association between Dw4/Dw14
compound heterozygosity andl the development of erosions
has been reported previously; unfortunately, they do not cite
a reference. To the best of our knowledge no previous study
of patients with early arthritis; has investigated this characteristic. Of course, as we mentioned in our article, patients
with established longstanding rheumatoid arthritis have a
disproportionate representatioa of the Dw4/Dw14 genotype.
We showed that patients who present with this genotype
have an extremely high risk of developing severe erosive
disease, which is a quite separate issue.
Thus, the simple message is that the ACR criteria are
good for predicting persistence and that RF and the conserved HVR3 of certain HLA-DRB1 genes are good for
predicting severity. We would stress again that this is
particularly important in clinical practice.
Paul Emery, MD, FRCP
Jeff Faint, BSc
Andrew Birley, PhD
Andrew Cough, MRCP
Darrell Pilling, BSc
Mike Salmon, PhD
University of Birmingham
Birmingham, U K
Improved methotrexate patient information
To the Editor:
We would like to voice our concern over the printed
standardized information sheet that many pharmacies furnish to patients with their methotrexate tablets. Those
instructions have recently caused patients to drop out of a
clinical trial and to disregard physicians' instructions.
1. It would be preferable to state that this medication may
be used to treat certain types of cancer, psoriasis, and
autoimmune diseases.
2. The warning against taking vitamins containing folic
acid is not valid for low-dose therapy. It has been
shown that low-dose folic acid supplements (5 mg, 7
mg, or 27.5 mg weekly) lessen the toxic manifestations
of methotrexate therapy for rheumatoid arthritis without altering the efficacy (1,2). This has also been shown
in the use of methotrexate for the treatment of psoriasis
(3).
3. The statement about immunization applies to methotrexate dosages used for cancer chemotherapy, not
rheumatoid arthritis.
We have communicated our concerns to Medi-Span,
who maintains the Patient Drug Education DatabaseTM.
They have revised the indication(s) statement, removed the
sentence recommending avoidance of folk acid supplements, and removed the cautionary statement about immunizations from the Rheumatrex monograph. In the chemotherapy monograph, the immunization phrase will be
reworded to indicate that patients should check with their
physicians before receiving any immunizations. These revisions will help reduce unwarranted patient concerns. Clinicians should make the effort to be familiar with the instructions given to patients about their medications.
Sarah L. Morgan, MD, RD, FACP
Graciela S. Alarcon, MD, MPH
Larry Moreland, MD
The University of Alabama at Birmingham
1. Morgan SL, Baggott JE, Vaughn WH, Young PK, Austin JV,
Krumdieck CL, Alarc6n GS: The effect of folic acid supplementation on the toxicity of low-dose methotrexate in patients with
rheumatoid arthritis. Arthritis Rheum 33:9-18, 1990
2. Morgan SL, Baggott JE, Vaughn WH, Austin JS, Veitch TA, Lee
BOOK REVIEWS
JY, Koopman WJ, Krumdieck CL, Alarc6n GS: Supplementation with folk acid during methotrexate therapy for rheumatoid
arthritis: a double-blind, placebo-controlled trial. Ann Intern
Med 121:833-841, 1994
3. Duhra P: Treatment of gastrointestinal symptoms associated with
methotrexate therapy for psoriasis. J Am Acad Dermatol28:46&
469, 1993
Reply
To the Editor:
Medi-Span’s Patient Drug Education Database’“
monographs are careful distillations of information (usually
under one page in length) most important for the proper and
safe use of medication by a wide variety of patients. The
monographs are intended to supplement verbal medication
counseling provided to patients by health care professionals.
875
Methotrexate creates a unique challenge because
some brands are marketed for the treatment of cancer, and
other brands are marketed for the treatment of rheumatoid
arthritis. The information in our earlier versions of the
methotrexate monographs was consistent with package inserts and various drug therapy references. However, we
modified the content of the monographs to reflect current
medical practices that are supported by scientific data.
We are grateful to Drs. Morgan, Alarcon, and Moreland for helping us address 1.his issue as we continue our
initiative to provide the highest quality of electronic patient
drug education available.
Mark Millikan, Pharm D
Medi-Span
Indianapolis, IN
BOOK REVIEWS
Autoimmune Diseases: Focus on Sjogren’s Syndrome. Edited
by David A . Isenberg and Angela C . Horsfall. Oxford, BIOS
Scientific Publishers, 1993. 240 p p . Illustrated. Indexed.
$99.00.
The proceedings of 4 international symposia on Sjogren’s syndrome (SS) have been published, and the fifth such
meeting will soon be held in Amsterdam. Primary SS is
recognized today as a disease entity distinct from rheumatoid arthritis. SS and systemic lupus erythematosus (SLE)
do occur together, and, in fact, some patients have an
SS/SLE overlap syndrome.
The current volume represents the proceedings of a
meeting held in London in December 1993. This book is
up-to-date, well-written, and generally informative. The
editors have selected an excellent line-up of topics and
appropriate internationally recognized authorities to address
them. Even apoptosis, the current “hot topic” in clinical and
basic immunology, is mentioned in the book. There are some
original data from the laboratory of Pierre Youinou and an
analysis of the cost of autoimmunity by David Isenberg and
colleagues. There is an excellent review of viruses in SS, a
consideration of the importance of cell adhesion in autoimmune rheumatic diseases, an authoritative analysis of
immunogenetics, and a discussion of the newer animal
models for SS. Of particular interest was the focus on
monoclonal lymphoid populations and the excellent discussion of mucosa-associated lymphoid tissues and tumors
(MALT).
I learned some new things from this lively and timely
tome. Even if you are not an SS aficionado, you will find it
a delightful read for a short plane ride.
Norman Talal, MD
The University of Texas
Heulth Science Center
at San Antonio
Living with Lupus: All the ]Knowledge You Need to Help
Yourself. Sheldon P . Blau an’dDodi Schultz. Reading, MA,
Addison- Wesley, 1993. 264 p p . $9.57.
Living with Lupus fills a need for an informative book
on the everyday problems encountered by patients with
systemic lupus erythematosns (SLE). The book is quite
thorough.
The introduction provides a historical review of the
derivation of the disease name and an overview of the
favorable change in prognosis that we have witnessed in the
past 30 years.
Its first chapter paints vignettes that describe the
disease onset in 7 women. It moves on to discuss the clinical
manifestations of SLE, curreint ideas about its etiology, and
accurately describes concepts about the proper interpretation of diagnostic tests and laboratory studies that are
employed to follow the disearse course. The book contains
good sections about medications and procedures that might
have to be employed in its treatment.
The book stresses the need for expert (usually rheu-
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