Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis.

Abstract

To investigate the therapeutic value of azathioprine as monotherapy or combined with other immunosuppressive drugs for uveitis in patients with juvenile idiopathic arthritis (JIA).
A retrospective multicentre study including 41 children with JIA (28 (68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis. Azathioprine was used to treat uveitis that was active in patients receiving topical or systemic corticosteroids, methotrexate or other immunosuppressive drugs. The primary end point was assessment of uveitis inactivity. Secondary end points comprised dose sparing of topical steroids and systemic corticosteroids, and immunosuppression.
At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as combination therapy. During the entire azathioprine treatment period (mean 26 months), inactivity was obtained in 16/26 patients (61.5%) with monotherapy and in 10/15 (66.7%) when combined with other immunosuppressives (p=1.0). With azathioprine, dosages of systemic immunosuppression and steroids could be reduced by ≥ 50% (n=12) or topical steroids reduced to ≤ 2 drops/eye/day in six patients. In three patients (7.3%), azathioprine was discontinued because of nausea and stomach pain. Conclusions Azathioprine may be reconsidered in the stepladder approach for the treatment of JIA-associated uveitis. The addition of azathioprine may also be beneficial for patients not responding properly to methotrexate.

Full text

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Azathioprine as a treatment option for uveitis in patients with juvenile
idiopathic arthritis
J.C. Goebel, M. Roesel, C. Heinz, H. Michels, G. Ganser,
A. Heiligenhaus

Corresponding author
Prof. Dr. Arnd Heiligenhaus
Department of Ophthalmology at St. Franziskus-Hospital
Hohenzollernring 74
48145 Muenster, Germany
Phone: #49-251-933080
Fax: #49-251-9330819
e-mail: arnd.heiligenhaus@uveitis-zentrum.de

Jan Christian Goebel, Martin Roesel, Carsten Heinz
Department of Ophthalmology, Uveitis Center at St. Franziskus-Hospital,
Muenster, Germany
Hartmut Michels
German Center of Pediatric and Adolescent Rheumatology, Garmisch-
Partenkirchen, Germany
Gerd Ganser
Department of Pediatric Rheumatology, St. Josef Stift, Sendenhorst, Germany

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Key Words: immunosuppression, juvenile idiopathic arthritis, azathioprine,
uveitis




2497 words

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ABSTRACT

Aim: To investigate the therapeutic value of azathioprine as monotherapy or
combined with other immunosuppressive drugs for uveitis in patients with
juvenile idiopathic arthritis (JIA).
Methods: Retrospective multi-center study including 41 JIA children (28
(68.2%) female) with unilateral or bilateral (n=28) chronic anterior uveitis.
Azathioprine was used to treat uveitis that was active in patients on topical or
systemic corticosteroids, MTX, or other immunosuppressive drugs. The
primary endpoint was assessment of uveitis inactivity. Secondary endpoints
comprised dose sparing of topical steroids and systemic corticosteroids and
immunosuppression.
Results: At 1 year, uveitis inactivity was achieved in 13/17 (76.5%) of
patients by using azathioprine as systemic monotherapy and in 5/9 (56.6%) as
combination therapy. During the entire azathioprine treatment period (mean
26 months), inactivity was obtained in 16/26 patients (61.5%) with
monotherapy and in 10/15 (66.7%) when combined with other
immunosuppressives (p=1.0). With azathioprine, dosages of systemic
immunosuppression and steroids could be reduced by ≥50% (n=12) or topical
steroids reduced to ≤2 drops/eye/day in 6 patients. In 3 patients (7.3%),
azathioprine was discontinued because of nausea and stomach pain.
Conclusions: “Azathioprine may be reconsidered in the step-ladder approach
for the treatment of JIA-associated uveitis. The addition of azathioprine may
also be beneficial for patients not responding properly to methotrexate.”

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Introduction
Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory
rheumatic disease in childhood and begins before 16 years of age. JIA is
characterized by a chronic inflammation of the joints, which may lead to joint
destruction.[1-3] The most frequent form of eye involvement in JIA is uveitis,
with an estimated incidence between 10 and 18%.[4-5] Uveitis is
characterized by chronic inflammation of the iris and ciliary body. The course
of the disease varies highly. A severe and vision-threatening course develops
in approximately one third of patients, and the complication rate rises during
the chronic course of disease.[5-7]
The aim of treatment is to completely abolish active inflammation in the eye.
Therapy is usually started with topical corticosteroids, occasionally combined
with systemic corticosteroids. However, in approximately 30% of patients the
uveitis remains active, so that immunosuppressive drugs are required.
Methotrexate is the first-choice immunosuppressive, cyclosporine A,
azathioprine or the anti-tumor necrosis factor (TNF) alpha inhibitors represent
other options.
Azathioprine is a well-known purine synthesis inhibitor that is widely used in
organ transplantation and several autoimmune diseases, e.g., rheumatoid
arthritis. A favorable response has also previously been noted in the treatment
of arthritis in JIA patients.[8-9]
Azathioprine has only occasionally been utilized to treat uveitis in JIA
patients. Indeed, only small case series have been reported in the literature,
describing experience with azathioprine in only few children. [9-10] In this

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paper, we summarize our observations using azathioprine in treating 41
patients with JIA-associated uveitis.

Patients and Methods
All patients in this study fulfilled the classification of juvenile idiopathic
arthritis (JIA) in agreement with the International League of Associations for
Rheumatology (ILAR) criteria.[3] The 41 children were treated with
azathioprine for severe chronic anterior uveitis. The cohort included
consecutive patients who were started on azathioprine treatment for uveitis
between 1995 and 2007. Charts were reviewed retrospectively. The design of
the work conforms to the standards currently applied in Germany. No
institutional review board approval is required for chart review studies.
Rheumatologic examinations and diagnostic procedures included a review of
systems, laboratory tests (e.g., antinuclear antibodies, rheumatoid factor, and
HLA B 27), urine analysis, and chest x-ray, if necessary. An infectious
etiology was excluded if serological tests for EBV, CMV, HSV, HZV,
treponema, toxoplasma, and toxocara and the tuberculosis skin test were
negative.
Patients with other uveitis entities, such as intermediate, Fuchs heterochromic
cyclitis, and infectious uveitis syndromes, were excluded from the study. A
standardized ophthalmic database was applied for the analysis. The
ophthalmic assessment included best-corrected visual acuities (BCVA), slit-
lamp examination, tonometry (Goldmann), and funduscopy.