Systemic indications

Adalimumab has been evaluated in a number of clinical trials for RA,49,50 Crohn’s disease,10,51 ankylosing spondylitis,52 and psoriatic arthritis.53,54 Initially evaluated as adjunctive therapy to RA patients on methotrexate, adalimumab demonstrated rapid improvement in American College of Rheumatology 20 scores at 1 week of administration. The PREMIER trial compared combination adalimumab plus methotrexate therapy with either medication given alone and found that the combination of adalimumab plus methotrexate was superior to adalimumab or methotrexate monotherapy.55

Ophthalmic indications

The efficacy of adalimumab for uveitis has been reported in several retrospective series for adults and pediatric patients. Its efficacy for Behçet’s disease-associated uveitis was reported in two retrospective reports.56,57 Mushtaq et al. reported 3 patients with Behçet’s diseaseassociated uveitis who were successfully switched from infliximab to adalimumab while in clinical remission. Follow-up was variable in this series, varying from 11 to 24 months; however, intraocular inflammation remained well controlled during the follow-up period. Administration of adalimumab for severe Vogt–Koyanagi–Harada syndrome allowed the successful tapering of corticosteroid and cyclosporine in one case report.58

Vazquez-Cobian et al.59 reported the successful treatment of pediatric uveitis (9 JIA-associated and 5 idiopathic) with adalimumab. In their series, adalimumab was well tolerated with no reports of serious adverse events. A total of 21 of 26 (80%) eyes with inflammation at baseline experienced a decrease in intraocular inflammation while 4 (15%) eyes remained stable and 1 (4%) eye worsened. A decrease in topical corticosteroid use was observed in 11 of 14 patients (79%) while 4 of 14 patients (29%) completely discontinued topical medications. In addition, other corticosteroid-sparing medications were decreased in a number of patients during the period of adalimumab therapy. Another retrospective series by Biester et al.60 described the efficacy of adalimumab for uveitis in 18 pediatric patients. Seventeen patients were JIA-associated while 1 was idiopathic. Ophthalmic efficacy was demonstrated in 16 of 18 patients (88%). Adalimumab also appeared effective or mildly effective for JIA-associated arthritis in 13 of 16 patients (81%) during the follow-up period.

randomized clinical trials, open-label extensions, phase IIIb trials, and postmarketing reporting of adverse events in the USA were collected. Reported adverse events included serious infections (5.1 events/100 patient-years (PYs)), lymphoma (0.12/100 PYs), tuberculosis (0.27/100 PYs), opportunistic infections (0.08 events/100 PYs), demyelinating diseases (0.08/100 PYs), systemic lupus erythematosis/lupus-like syndrome (0.10/100 PYs), and congestive heart failure (0.28/100 PYs). The incidence of lymphoma did not appear to be significantly higher in patients treated with adalimumab than in RA patients who were naïve to anti-TNF-α therapy; however, the rate of lymphoma may be higher in RA patients compared to the general population, particularly in patients with severe RA. Adverse events reported in patients with ophthalmic inflammatory disease treated with adalimumab have included injection site reactions, herpes simplex keratitis, and elevation of liver enzymes requiring cessation of therapy.60

Drug interactions

Adalimumab is currently approved for RA and psoriatic arthritis in combination with methotrexate and low-dose prednisone. Live viruses should be avoided in patients on adalimumab and its use may decrease the immunologic protection conferred by live attenuated vaccines. No clear data are available for its use in combination with other biologic agents, so this combination should be avoided until further studies have demonstrated efficacy and safety.

Summary

Like infliximab, adalimumab has been used successfully in clinical trials for the treatment of RA, Crohn’s disease, ankylosing spondylitis, and psoriatic arthritis. Ophthalmic studies are limited, but suggest that this agent may be effective for pediatric uveitis, Behçet’s diseaseassociated uveitis, and other uveitic entities in which TNF-α may play a role. Because it is fully human (cf. chimeric structure of infliximab), it is likely that this medication is less immunogenic than infliximab. The subcutaneous route of administration offers advantages over the intravenous route of infliximab with the inherent risks of intravenous medication administration, as well as the higher costs associated with hospitalization. Further studies are needed to determine its relative efficacy and safety compared to infliximab therapy for ophthalmic inflammatory diseases.

Contraindications

Adalimumab is contraindicated in patients with known hypersensitivity to the medication or any of its components and in patients at risk for sepsis. In addition, the medication should be avoided in patients with a history of multiple sclerosis, active infection, or malignancy.

Ocular toxicity

Herpes simplex keratitis has been reported in one 5-year-old female patient treated with adalimumab for pauciarticular JIA-assoicated uveitis.60

ETANERCEPT (ENBREL)

Pharmacology and mechanism

The third FDA-approved TNF antagonist is etanercept, which differs structurally from the monoclonal antibody structure of infliximab and adalimumab. Etanercept is a recombinant TNF-α receptor fusion protein composed of the constant (Fc) portion of human IgG1 and two copies of the extracellular ligand-binding portion of TNF receptor p75.

Etanercept is given via subcutaneous injection at a dose of 25–50 mg twice weekly. Its elimination half-life is 102 hours following a single subcutaneous dose of 25 mg.63

Systemic toxicity

Injection site reactions appear to be the most commonly reported adverse event and occur in up to 10% of patients treated. In an efficacy and safety study of adalimumab for ankylosing spondylitis, the number of adverse events was higher in patients receiving subcutaneous adalimumab 40 every other week than in those receiving placebo. The percentage of patients who experienced infectious complications was higher in the patients receiving adalimumab, but this finding was not statistically significant. No occurrences of latent tuberculosis reactivation, lupus-like syndromes, congestive heart failure, or secondary malignancies were reported.61 In a postmarketing surveillance study of RA patients, Schiff et al.62 reported that adalimumab appeared to be relatively safe and well tolerated. In their study, safety data from

Systemic indications

Etanercept has demonstrated efficacy for a number of systemic auto­ immune conditions, including RA,64,65 JIA,66 ankylosing spondylitis,67 and psoriatic arthritis.68 However, its efficacy in the treatment of ocular inflammatory disease has been variable in limited series.

Ophthalmic indications

Smith et al.69 reported the results of a randomized, controlled, masked trial of etanercept for JIA-associated anterior uveitis. In their study, no apparent difference in anterior-segment inflammation was observed between etanercept and placebo.70 Another prospective study of