Infliximab therapy clinical trial - high adverse reactions

[Mike Bartolatz]

Data: Prospective trial of infliximab therapy for uveitis
Posted: 10/10/05 12:35 pm
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A : prospective trial of infliximab therapy for refractory uveitis preliminary safety and efficacy outcomes.

Arch Ophthalmol. 2005 Jul;123(7):903-12. Suhler EB, Smith JR, Wertheim MS, Lauer AK, Kurz DE, Pickard TD, Rosenbaum JT. Uveitis and Retina Divisions, Casey Eye Institute, 3375 SW Terwilliger Blvd., Portland, OR 97239, USA.

OBJECTIVE: Infliximab, a monoclonal antibody against tumor necrosis factor alpha, is approved by the US Food and Drug Administration for treatment of numerous autoimmune disorders. We conducted a prospective, open-label phase 2 clinical trial to assess the effectiveness of infliximab in treating refractory autoimmune uveitis.

METHODS: We prospectively enrolled 23 patients from the uveitis clinic of the Casey Eye Institute, Portland, Ore, into this trial. All patients meeting eligibility criteria received 3 infliximab infusions at weeks 0, 2, and 6. Clinical success was ascertained at week 10. Patients meeting initial criteria for success received an infusion at week 14 and every 8 weeks thereafter, with dose escalation permitted for breakthrough inflammation, and underwent outcome measurements at week 50.

RESULTS: All patients underwent outcome assessment at week 10. Eighteen (78%) of these subjects met criteria for clinical success at this time. Success was judged by the composite clinical end point of visual acuity, control of intraocular inflammation, ability to taper concomitant medication therapy, and improvement in inflammatory signs on fluorescein angiography and/or ocular coherence tomography. Successful grading required improvement in at least 1 of 4 subcomponents and worsening in none. Seven of 14 patients enrolled for 1 year continued infliximab therapy and maintained their successful grading. Five did not complete 1 year of treatment because of significant adverse events, and 2 terminated treatment early for reasons unrelated to the study.

Serious adverse events that were potentially related to infliximab included pulmonary embolus, congestive heart failure, lupus-like reaction in 2, and vitreous hemorrhage in 2 patients. Antinuclear antibodies developed in 15 of 20 enrolled patients receiving 3 or more infusions.

CONCLUSIONS: Infliximab was an effective short-term immunosuppressive agent in most of the patients, with 18 of 23 meeting criteria for clinical success at week 10. Infliximab was effective in the long term in all patients able to complete 50 weeks of therapy. Although some patients achieved clear benefit, the rate of serious toxic effects was unexpectedly high.

Further long-term studies are warranted to determine the safety and efficacy of infliximab in treating intraocular inflammation.


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