Abstract
Purpose
To compare tacrolimus monotherapy with tacrolimus and prednisone therapy for the maintenance of disease remission in subjects with noninfectious posterior segment intraocular inflammation (PSII).
Design
Randomized, controlled, phase 2b, open-label, dual-center noninferiority trial.
Participants
Fifty-eight patients with sight-threatening PSII.
Methods
Patients requiring a second-line systemic immunosuppressive agent to control their PSII were treated with therapeutic doses of oral tacrolimus. Those subjects who subsequently were able to taper their prednisone dose to 10 mg daily without disease reactivation were assigned randomly either to stop prednisone or to continue 7.5 to 10 mg prednisone daily for 9 months.
Main Outcome Measures
Change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) and rate of patient withdrawal resulting from treatment inefficacy or intolerance.
Results
Thirty-five patients successfully tapered their prednisone to 10 mg daily. Of these, 16 were allocated randomly to receive tacrolimus monotherapy and 19 to continue taking prednisone and tacrolimus dual therapy. The difference in the mean change in VA for monotherapy compared with the dual therapy group was less than 1 logMAR letter (logMAR, -0.008; 95% confidence interval, -0.108 to 0.092; P = 0.870). The proportion of patients who tolerated treatment and maintained disease remission for 9 months after randomization also was similar in both groups (monotherapy, 62.5%; dual therapy, 68.4%; P = 0.694). All monotherapy treatment failures were the result of disease reactivation, whereas 50% of dual-therapy failures were the result of drug intolerance.
Conclusions
This study provides preliminary evidence that corticosteroids can be withdrawn in tacrolimus-treated patients who are able to achieve control of PSII with 10 mg prednisone daily, and any advantage of dual therapy in the prevention of disease reactivation was offset by its greater treatment intolerance. These findings support the further evaluation of corticosteroid-free treatment in future phase 3 trials (International Standard Randomised Controlled Trial Number Register identification, ISRCTN46576063).
Financial Disclosure(s)
Proprietary or commercial disclosure may be found after the references.
To compare tacrolimus monotherapy with tacrolimus and prednisone therapy for the maintenance of disease remission in subjects with noninfectious posterior segment intraocular inflammation (PSII).
Design
Randomized, controlled, phase 2b, open-label, dual-center noninferiority trial.
Participants
Fifty-eight patients with sight-threatening PSII.
Methods
Patients requiring a second-line systemic immunosuppressive agent to control their PSII were treated with therapeutic doses of oral tacrolimus. Those subjects who subsequently were able to taper their prednisone dose to 10 mg daily without disease reactivation were assigned randomly either to stop prednisone or to continue 7.5 to 10 mg prednisone daily for 9 months.
Main Outcome Measures
Change in logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) and rate of patient withdrawal resulting from treatment inefficacy or intolerance.
Results
Thirty-five patients successfully tapered their prednisone to 10 mg daily. Of these, 16 were allocated randomly to receive tacrolimus monotherapy and 19 to continue taking prednisone and tacrolimus dual therapy. The difference in the mean change in VA for monotherapy compared with the dual therapy group was less than 1 logMAR letter (logMAR, -0.008; 95% confidence interval, -0.108 to 0.092; P = 0.870). The proportion of patients who tolerated treatment and maintained disease remission for 9 months after randomization also was similar in both groups (monotherapy, 62.5%; dual therapy, 68.4%; P = 0.694). All monotherapy treatment failures were the result of disease reactivation, whereas 50% of dual-therapy failures were the result of drug intolerance.
Conclusions
This study provides preliminary evidence that corticosteroids can be withdrawn in tacrolimus-treated patients who are able to achieve control of PSII with 10 mg prednisone daily, and any advantage of dual therapy in the prevention of disease reactivation was offset by its greater treatment intolerance. These findings support the further evaluation of corticosteroid-free treatment in future phase 3 trials (International Standard Randomised Controlled Trial Number Register identification, ISRCTN46576063).
Financial Disclosure(s)
Proprietary or commercial disclosure may be found after the references.
| Original language | English |
|---|---|
| Pages (from-to) | 1223-1230 |
| Number of pages | 8 |
| Journal | Ophthalmology |
| Volume | 119 |
| Issue number | 6 |
| Early online date | 3 Mar 2012 |
| DOIs | |
| Publication status | Published - Jun 2012 |