A randomized, placebo-controlled clinical trial of tacrolimus ophthalmic suspension 0.1% in severe allergic conjunctivitis

Abstract

Aims: To examine the efficacy of tacrolimus ophthalmic suspension 0.1% in treating severe allergic conjunctivitis.

Methods: This was a multicenter, randomized, double-masked, placebo-controlled clinical trial. Fifty-six patients with severe allergic conjunctivitis in whom topical antiallergic agents and corticosteroids had been ineffective were randomized to tacrolimus or placebo treatment. Patients were treated either with tacrolimus or placebo twice-daily for 4 weeks. Severity of objective signs in palpebral and bulbar conjunctiva, limbus, and corneal involvement was assessed using 4 grades. Seven subjective symptoms were evaluated by visual analog scale (VAS) assessment. The primary efficacy endpoint was change in the total score of objective signs at the end of treatment. The secondary efficacy endpoints included change in the score for each objective sign and change in the VAS for each subjective symptom. Safety was assessed based on the severity and the incidence of adverse events.

Results: Mean change from baseline in total score for objective signs was significantly greater in the tacrolimus (-5.6 + or - 5.1) than in the placebo group (-0.1 + or - 4.5; P < 0.001). Tacrolimus significantly improved giant papillae (P = 0.001) and corneal involvement (P = 0.005). Five subjective symptoms (itching, discharge, hyperemia, lacrimation, and foreign body sensation) were significantly better in the tacrolimus than in the placebo group. The most frequent treatment-related adverse event in the tacrolimus group was mild ocular irritation upon topical instillation, which was well-tolerated.

Conclusion: Tacrolimus ophthalmic suspension 0.1% is effective in treating severe allergic conjunctivitis.

FIG. 1.

(A) Mean change from baseline in total score for objective signs. (B) Mean change from baseline in total score for objective signs in atopic keratoconjunctivitis (AKC) patients. (C) Mean change from baseline in total score for objective signs in vernal keratoconjunctivitis (VKC) patients. Significance of differences was evaluated by 2-sample t-test compared with placebo group. ( ): patient number. Vertical bars: standard deviation.

FIG. 2.

Distributions of scores for giant papillae, corneal involvement, palpebral conjunctival hyperemia, and bulbar conjunctival hyperemia. Significance of differences was evaluated by Mann–Whitney U-test for change in score compared with placebo group. ( ): patient number.

FIG. 3.

(A) Giant papillae at baseline in a 9-year-old male vernal keratoconjunctivitis (VKC) patient (case A). (B) After 4-week treatment with tacrolimus ophthalmic suspension in case A. Most giant papillae became flat (score 1+) and less inflamed. (C) Shield ulcer at baseline in 28-year-old female atopic keratoconjunctivitis (AKC) patient (case B). (D) After 4-week treatment with tacrolimus ophthalmic suspension in case B. Shield ulcer disappeared.

FIG. 4.

Visual analog scale (VAS) for each subjective symptom. The figure shows mean (SD) change from baseline in each symptom at end of treatment. Significance of differences was evaluated by 2-sample t-test compared with placebo group. Range for each symptom: 0–80 mm. ( ): patient number. Vertical bars: standard deviation.