Conversion of cyclosporine to tacrolimus in stable renal allograft recipients: Quantification of effects on the severity of gingival enlargement and hirsutism and patient-reported outcomes
Declaration of conflict of interest: Drs Cottrell, Nicholls, Fraser and Varigos, as well as Ms Sharp and Tripodi have no primary financial arrangements with commercial companies that produce or sell products that are the subject of the study reported in the manuscript, or with competitors of such companies. Professor Walker serves on Clinical Advisory Boards for both Janssen-Cilag and Novartis. All are supported investigators of Janssen-Cilag Pty Ltd, Sydney, Australia. Dr Butcher is an employee of Janssen-Cilag Pty Ltd, which markets PROGRAF®™, a form of tacrolimus. PROGRAF®™ is a registered trademark of Astellas Pharma Inc.
SUMMARY:
Background: Cyclosporine-induced side-effects such as gum enlargement and hirsutism potentially limit its effectiveness as a calcineurin-antagonist if these effects contribute to a lack of compliance. Although the differences in incidence of these effects are widely recognized, few studies are available to show the extent of reduced gum enlargement and hirsutism in patients converted from cyclosporine to tacrolimus. This study aimed to determine the efficacy and safety and patient-reported outcomes of such conversions.
Methods: Twenty-one consecutive cyclosporine-treated renal-transplant recipients with evidence of gingival enlargement were randomized into two arms: 10 continued to receive cyclosporine, 11 were converted to tacrolimus. Mean differences (0–3, 0–6, 0–9 and 0–12 months) in periodontal indices (gingival inflammation, plaque, pocket depth, gingival enlargement), hirsutism, serum creatinine and glucose and subjective differences in the patient's rating of disfigurement due to hirsutism and gingival enlargement were recorded.
Results: There were no differences in baseline periodontal scores between the two groups. Tacrolimus-treated subjects had significantly reduced pocket depth and gingival enlargement measures (Pocket Depths: −0.40 ± 0.58 vs 0.30 ± 0.35, P < 0.01; Gingival Enlargement Index: −1.12 ± 0.83 vs−0.10 ± 0.89, P < 0.05; tacrolimus vs cyclosporine, respectively), and decreased subjective disfigurement compared with the cyclosporine-treated group over the 12 months. While there was no difference in objective hirsutism scores between the two groups, tacrolimus-treated patients reported a significant improvement and cyclosporine-treated patients a significant worsening in their degree of disfigurement at the end of 12 months. There were no differences in creatinine or glucose levels.
Conclusion: Conversion from cyclosporine to tacrolimus in stable renal-transplant recipients with cyclosporine-induced gingival enlargement can be achieved safely and with measurably good effect.
