The Medical Journal of Basrah University

Abstract

ABSTRACT
Background: The present study is based on two assumptions. First is the racial and ethnic differences in the
presentation of rheumatoid arthritis (RA) and its response to drugs. And the second is the interaction between
nonsteroidal anti-inflammatory drugs (NSAIDs) and the disease modifying antirheumatic drugs (DMARDs)
particularly methotrexate (MTX) with the possibility of enhanced toxicity.
Objectives: to investigate the efficacy and toxicity of MTX alone or in combination with diclofenac in the treatment
of RA.
Methods:
Design: A three month randomized comparative clinical trial
Setting: Rheumatology Unit at the Teaching Hospital and the Department of Pharmacology, College of Medicine,
University of Basrah, Basrah, Iraq.
Patients: Patients with moderate to severe RA were classified into, Group I: received MTX (7.5 mg orally as a single
weekly dose). Group II: received MTX single weekly dose plus diclofenac sodium 100 SR tablets once daily
Measurements and evaluation
Pain, morning stiffness, joint function (number of the swollen and tender joints), patients and physician global
assessment, radiological evaluation (according to modified Sharp score for joint space narrowing and erosions), ACR
criteria for progression and remission of RA, laboratory findings (complete blood picture and ESR, blood groups, Hb
electrophoresis, AST, ALT, blood urea) and drug adverse effects were evaluated.
Results: Twenty eight patients with moderate to severe RA were randomly allocated into two treatment groups as
cited in the Methods. Only 25 patients managed to complete the 12 week treatment course. Oral MTX (7.5 mg)
resulted in a statistically significant clinical improvement after 12 weeks of treatment. The improvement seems to be
time dependent. The average percent improvement in six clinical parameters mounted to about 35% compared to the
baseline measurements. The 20% improvement at 12 weeks of treatment using ACR criteria involved 42.8% of
patients. Radiological findings (joint space narrowing and erosion) increased slightly by only 5.7% over the 12 week
treatment period. No significant change in all laboratory parameters measured. No important side effects peculiar to
MTX could be figured out. Concurrent administration of diclofenac (sustained release formulation) with MTX
resulted in a paradoxical finding. Instead of enhancing efficacy or toxicity of MTX, diclofenac reduced the efficacy of
MTX from 35.25% to only 15.78% at the end of the treatment period. The two groups, however, differed in some
aspects e.g. disease duration and severity, and the type of blood groups which might possibly have contributed to this
difference. The ACR20 in the combination group is 36.3% (compared to 42.8% in MTX group). Radiological findings
progressed by 48.3% in the joint space narrowing and erosion. When results of MTX and MTX+diclofenac groups
were analyzed according to disease severity and blood groups, it was found that the response of patients with severe
but not moderate disease was comparable in the two groups. Blood group (A) seems to be associated with enhanced
response and group (O) with a reduced one.
Conclusion: Methotrexate 7.5 mg as a single oral dose per week produced a significant clinical improvement over the
12 week treatment period. The drug seems to be well tolerated with no important adverse effects. In contrast to what
is expected, sustained formulation of diclofenac sodium reduced the efficacy of MTX. The latter finding, if proved to
be true, could have an important clinical implication.