Rheumatology Advance Access originally published online on April 19, 2007
Rheumatology 2007 46(6):1042-1043; doi:10.1093/rheumatology/kem052
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Efficacy of the IL-1 receptor antagonist, anakinra, for the treatment of diffuse anterior scleritis in rheumatoid arthritis. Report of two cases
Section of Rheumatology, Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy
Correspondence to: Paolo Sfriso. E-mail: paolo.sfriso{at}unipd.it
SIR, Rheumatoid arthritis (RA) is a systemic disease with clinical manifestations often affecting several organs. Scleritis is a well recognized and severe manifestation of rheumatoid eye disease. Scleritis is defined as inflammation of the sclera, and it has a characteristic clinical picture. It is typically a severe painful inflammatory process centered in the sclera that may involve the cornea, adjacent episclera and underlying uvea; it poses a significant threat to vision. Symptoms of anterior scleritis are pain, tearing and photophobia. Progression to perforation of the eyeball can also occur [1].
We describe two patients with RA and scleritis successfully treated with anakinra: one patient with severe anterior scleritis, infliximab was ineffective and the other patient developed anterior scleritis during exposure to etanercept.
The first patient was a 50-yr-old Caucasian woman with seropositive RA of 20 yrs duration. She had a 1-yr history of left eye diffuse anterior scleritis and was initially treated with oral prednisolone (15 mg/day) and topical prednisolone acetate 1%, without effect for over 3 months. Oral prednisolone was increased to 50 mg daily and methotrexate 10 mg/week added. After 8 weeks on this regimen, the lack of effect led to the additional supplement of oral ciclosporin (5 mg/kg/daily) whilst prednisolone was tapered to 25 mg. After a further 8 weeks, there was no significant improvement. The left eye diffuse anterior scleritis persisted and areas of necrotizing scleritis with blurring vision developed. In June 2002 infliximab was commenced at a dose of 5 mg/kg i.v. at 0, 2, 4 and 6 weeks followed by an infusion every 6 weeks, in combination with methotrexate 10 mg/week. After six infusions scleritis did not improve and visual acuity decreased to 2/10 in the left eye. Subsequently, anakinra was started at a dose of 100 mg/daily s.c. in combination with methotrexate (10 mg/week). After 8 weeks, the patient reported a dramatic remission of ocular signs and symptoms and visual acuity improved to 4/10.
Upon reduction of anakinra to alternate days, signs and symptoms of scleritis reappeared. Daily anakinra was reintroduced and, at present, over a period of 3 yrs, the scleritis has become completely quiescent, with only residual areas of scleral discolouration. Prednisolone has been reduced to 5 mg/day, and methotrexate continued at 7.5 mg/week. The peripheral joint disease also improved.
The second case was a 63-yr-old Caucasian woman with seropositive RA of 11 yrs duration. In November 2003, she has receiving etanercept (25 mg twice weekly) plus methotrexate (10 mg/weekly) combination therapy, with remission of the arthritis and no extra-articular manifestations. Fifteen months after the start of etanercept, and while the disease was still in remission, she developed left eye diffuse anterior scleritis. HLA-B27 was absent, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were 28 mm/h and 8 mg/l (n.v.<6 mg/l), respectively. Scleritis was initially treated with oral prednisolone (25mg/daily) and topical prednisolone acetate 1%. This treatment having no effect over 2 months, anakinra (100 mg/daily s.c.) in combination with methotrexate (10 mg/week) was started. After 6 weeks, the patient reported a dramatic remission of symptoms and signs of scleritis. At present, over a period of 1 yr, the scleritis has become quiescent and RA remains in remission; the patient still receiving anakinra 100 mg/day.
Tumour necrosis factor 
(TNF-) may play a role in experimental uveo-retinitis. In scleritis, both TNF and interleukin 1 (IL-1) released by the local inflammatory cell infiltrate has been associated with sclera destruction [2, 3]. Recently, it has been reported that human IL-1 receptor antagonist (IL-1Ra)—anakinra, suppresses immune-mediated ocular inflammation in mice [4].
Anti-TNF- treatment has been found to be successful in several intractable cases with juvenile rheumatoid arthritis (JRA)-associated uveitis, seronegative spondyloarthropathies, rheumatoid scleritis and Behçet's disease [5, 6]. On the other hand, ocular inflammation is paradoxically a potential, although rare, adverse event following the use of etanercept or infliximab in either previously uninvolved or inflamed eyes [5, 7].
These two cases illustrate that treatment with infliximab and etanercept, in the standard dosages, was effective in improving arthritis, but did not ameliorate or prevent ocular involvement in RA. Anakinra is the only agent presently approved for reducing IL-1 activities [8]. In our patients there was a rapid reduction of signs and symptoms of ocular inflammation following the initiation of anakinra, but in the first patient, each reappeared upon the dose reduction and they remitted again upon returning to daily dosing. The half-life of 100 mg of anakinra is <4 h and explains the requirement for daily treatment. Others have reported a similar flare of the systemic disease upon cessation of anakinra in adult [9] as well as in juvenile [10] Still's disease.
Our observation demonstrate the efficacy of anakinra in RA-associated diffuse anterior scleritis.
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The authors thank Prof. Charles A. Dinarello (University of Colorado Health Sciences Center, Denver, CO, USA) for his critical evaluation of the manuscript.
The authors have declared no conflicts of interest.
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