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Anti-tumour necrosis factor α treatment in chronic recurrent inflammation of the anterior segment of the eye in patients resistant to standard immunomodulatory treatment
  1. Y El-Shabrawi1,
  2. H Mangge2,
  3. J Hermann3
  1. 1Department of Ophthalmology, Karl-Franzens University, Graz, Austria
  2. 2Department of Laboratory Medicine and Paediatric Immunology/Rheumatology, Karl-Franzens University, Graz, Austria
  3. 3Department of Internal Medicine, Karl-Franzens University, Graz, Austria
  1. Correspondence to:
    Dr Y El-Shabrawi
    Department of Ophthalmology, Karl Franzens University Hospital, Auenbruggerplatz 4, 8036 Graz, Austria; yosuf.elshabrawikfunigraz.ac.at

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Recurrent or chronic anterior uveitis leads to a drop of vision below 20/50 in 23% of patients; 11% will eventually be legally blind.1,2 Thus the treatment of these patients still presents a challenge, and additional treatments are needed. In a previous study we found that anti-tumour necrosis factor α (anti-TNFα) treatment was highly efficient in a patient with an acute HLA-B27 associated uveitis.3 Thus we tested the efficacy of anti-TNFα treatment, consisting of a combined immunomodulatory drug and corticosteroids, in chronic inflammatory diseases of the anterior segment of the eye, non-responsive to standard anti-inflammatory treatment.

PATIENTS

Nine patients with uveitis with associated systemic disease were included (table 1). Eight of these patients had a rheumatic disease (five had a spondyloarthropathy (all were HLA-B27 positive), two had juvenile idiopathic arthritis (JIA; one Still’s disease, one antinuclear antibody (ANA) positive oligoarthritis)) and one patient had a necrotising sclero-uveitis associated with Wegener’s granulomatosis. One patient with uveitis with an associated tubulointerstitial nephritis (TINU) was also included. Disease modifying antirheumatic drug (DMARD) treatment was started at least three months before infliximab treatment. It consisted of methotrexate (MTX) in seven patients, of whom two received a combination of MTX and mycophenolate-mofetil. One patient received cyclophosphamide, and one leflunomide. Because the response was inadequate towards even combined immunosuppressant treatment (for example, MTX plus mycophenolate-mofetil) or because of the massive destructive activity of the disease (for example, necrotising sclero-uveitis) a quick acting active anti-inflammatory substance was needed. Because a quick response towards infliximab had been seen in a previous study, it was chosen again.3

Table 1

Clinical data and follow up in the patients treated. The visual acuity of the inflamed eye (right eye (od), left eye (os) or if both eyes had the same VA ou are listed)

RESULTS

Recurrent or chronic uveitis despite immunomodulatory treatment was present for a mean (SD) period of 8.6 (4.1) months before infliximab treatment. Infliximab was given at a dose of 3 mg/kg body weight at weeks 0, 2, and 6 in all but one patient who received only one infusion owing to a reaction after her first infusion. After anti-TNFα treatment the mean (SD) duration of the uveitis was 12.6 (11.7) days in HLA-B27 positive patients with uveitis and 38.5 (3.5) days in patients with JIA. In the patient with Wegener’s granulomatosis the time to remission was three months. The infliximab treatment had no effect in the patient with TINU. Patients with HLA-B27 associated uveitis remained in remission for an average of 5.5 (0.5) months. This 5.5 months’ duration of response was similarly achieved after re-treatment of these patients. In the patients with JIA the anti-inflammatory effect of TNFα blockage was much more moderate and only transient. In the patients with oligoarthritis the remission of uveitis after three infliximab infusions lasted for five weeks only and as seen in the patient with Still’s disease the uveitis became active again despite increasing the dose of infliximab after about 30 weeks. Thus it seems, as seen in the patient with Still’s disease, that the effect of TNFα treatment is reduced to some extent over the long term.

DISCUSSION

HLA-B27 associated uveitis as well as the sclero-uveitis in the patient with Wegener’s granulomatosis responded well to infliximab treatment. In all these patients a sustained anti-inflammatory effect was achieved. This is in accordance with the previously described positive effect of anti-TNFα treatment on the systemic manifestations of the spondyloarthropathies4,5 and Wegener’s granulomatosis.6 However, in both patients with chronic uveitis in association with JIA, the anti-inflammatory effect of infliximab on the eyes was not sustained. The overall moderate response towards TNFα blockade that we found in our patients with JIA is comparable with the results of a previous report.7 We are aware that only isolated cases are presented, but together the results of our study suggest that anti-TNFα treatment is not equally applicable to all forms of anterior uveitis but that ocular inflammations associated with the spondyloarthropathies, especially, are highly responsive to anti-TNFα treatment. Prospective, “blinded” studies will be required to examine these differences further.

REFERENCES

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