Optimizing the Use of Tumor Necrosis Factor α Inhibitors in Refractory Uveitis

We read with great interest the results of the phase II clinical trial on infliximab in refractory uveitis.¹ We congratulate Dr Suhler and colleagues on emphasizing pretreatment screening and the potential systemic complications.

Contrary to previous descriptions of tumor necrosis factor (TNF) α inhibitors for refractory uveitis,² it is implied that the stringent investigations and observations in this study projected more systemic complications leading to cessation of therapy in 50% of the patients. Some of the described complications may suggest preexisting risk factors or even an unrelated occurrence.

It would be interesting to know whether it is preferred practice to use infliximab as the first choice of TNF-α inhibitor in refractory uveitis and whether the treatments were switched to other TNF-α inhibitors when the patients developed adverse effects. There are studies suggesting different therapeutic efficacy for the available TNF-α inhibitors, namely, etanercept, infliximab, and adalimumab.³ However, there have been no comparative studies describing the clinical implications of these 3 drugs for specific ocular inflammatory conditions on which to base a preferential choice.

We describe 3 patients with refractory uveitis receiving TNF-α inhibitors who did not benefit from etanercept but responded well when switched to another TNF-α inhibitor. Etanercept was selected as the first choice so that patients could eventually administer their own treatment and avoid hospital admissions. Prior to switching treatment, etanercept was stopped for 2 weeks and the patients began receiving either methotrexate or a higher dose of steroids.

A 48-year-old woman with Behçet syndrome who had symptomatic uveitis while receiving high-dose oral prednisolone and cyclosporine was receiving 25 mg/kg of etanercept subcutaneously for 6 months with no improvement. She improved subjectively and clinically when the treatment was switched to infliximab. She has not developed any complications or antibodies at 6 months' follow-up, enabling the reduction of systemic steroid administration.

A 40-year-old woman with sarcoidosis-associated posterior uveitis was receiving etanercept for 9 months before switching to infliximab. She had improved vision and reduced vitreous activity after the second dose of infliximab. It might be premature to presume that this patient is unlikely to develop any drug-related complications, but she has shown marked clinical improvement.

A 21-year-old man with antinuclear antibody–negative and rheumatoid factor–negative juvenile rheumatoid arthritis with panuveitis who was receiving high-dose steroids and mycophenolate mofetil began receiving etanercept. Six months later, he continued to be symptomatic and his treatment was switched to adalimumab. He is clinically quiescent, and at 6 months' follow-up, he has not developed any adverse effects.

We have reduced the oral prednisolone dose satisfactorily in all of the 3 patients. Although the follow-up is limited, no patients have developed adverse effects or antinuclear antibodies. We feel that these patients would benefit from combined care with the rheumatologists so as to monitor systemic inflammation.

The different pharmacokinetic profiles and binding characteristics of these drugs as well as the pathophysiological findings of the disease could explain the altered response in these patients when their treatments were switched to an alternate TNF-α inhibitor. The merits of TNF-α inhibitors have been proven, but with variable efficacy profiles. Further studies based on the pathophysiological findings of uveitis are required before we can optimize the use of these drugs in ophthalmological practice.

Correspondence: Dr Sebastian, St. Paul's Eye Unit, Royal Liverpool University Hospital, Prescott Street, Liverpool Me L7 8XP, England (ranitheres@yahoo.com).

Financial Disclosure: None reported.