This prospective, open-label phase II clinical trial found adalimumab safe and effective for many patients with refractory uveitis. The 10-week success rate was 68 percent, although relapsing inflammation reduced treatment success at one year to 39 percent. There is an emerging need for additional data on the use of adalimumab and other tumor necrosis factor-α (TNFα) blockers alone and/or in combination with other immunosuppressives in the treatment of noninfectious uveitis.
The authors report results for 31 patients enrolled at three medical centers. The subjects were required to have vision-threatening noninfectious uveitis refractory to corticosteroids and at least one other immunosuppressive medication, or to be intolerant of such therapy. The majority of patients had panuveitis, posterior uveitis or intermediate uveitis. The most common etiologies included idiopathic uveitis and sarcoidosis, with a mixture of less common uveitis causes comprising the remainder of the cohort.
In contrast to other trials with TNFα blockers that utilize intravenous administration, 40 mg of adalimumab, a monoclonal antibody targeting TNFα, was administered subcutaneously every two weeks. The authors used a composite primary outcome that included four components: visual acuity, inflammatory control, medication tapering, and reduction in inflammatory signs on fluorescein angiography and OCT. Clinical response was defined by improvement in at least one parameter, worsening in none, and well-controlled intraocular inflammation. Week 10 responders were permitted to continue receiving adalimumab for the study duration of 50 weeks.
The primary outcome measures were achieved in 21 patients (67.7 percent) at 10 weeks. Only 12 of the 21 initial responders (39 percent of the initial study group) had a durable treatment response that lasted through the remaining year of follow-up. The authors note that the 10-week and 50-week response rates for adalimumab correlate with response rates for methotrexate, azathioprine, mycophenolate mofetil, cyclosporine and cyclophosphamide noted in other studies.
The most common reason for patients not continuing in the study after the initial 10 weeks was primary or secondary inefficacy. There was no significant trend of adverse events attributed to adalimumab administration. However, two serious adverse events occurred during the trial. One diabetic patient was hospitalized with a hypoglycemic coma and a second patient developed a cerebrovascular accident.
Limitations of this study include the lack of a control group, the use of corticosteroids along with adalimumab in some patients, and that the subjects were refractory to other treatment modalities and may have represented a more difficult-to-treat subset of uveitis patients.