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FK506 "rescue" therapy complicated by renal tubular acidosis in renal allograft recipients

Goh BL, Tan SY

Transplant Proc, 1998 Nov;30(7):3594-5.
PMID: 9838575
Matched MeSH terms: Tacrolimus/therapeutic use*
FK506 rescue therapy for acute renal allograft rejection

Goh BL, Morad Z, Cheah PL, Chua CT, Tan SY

Transplant Proc, 1998 Nov;30(7):3592-3.
PMID: 9838574
Matched MeSH terms: Tacrolimus/therapeutic use*
Childhood autoimmune liver disease: indications and outcome of liver transplantation

Chai PF, Lee WS, Brown RM, McPartland JL, Foster K, McKiernan PJ, et al.

J Pediatr Gastroenterol Nutr, 2010 Mar;50(3):295-302.
PMID: 20118802 DOI: 10.1097/MPG.0b013e3181bf0ef7

Graft rejection and disease recurrence are well-recognized complications of liver transplantation (LT) for autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (AISC). We describe indications and outcome of LT for childhood AIH and AISC.

Matched MeSH terms: Tacrolimus/therapeutic use
Pharmacogenotyping of CYP3A5 in predicting dose-adjusted trough levels of tacrolimus among Malaysian kidney-transplant patients

Hamzah S, Teh LK, Siew JS, Ahmad G, Wong HS, Zakaria ZA, et al.

Can J Physiol Pharmacol, 2014 Jan;92(1):50-7.
PMID: 24383873 DOI: 10.1139/cjpp-2013-0128

Tacrolimus (FK506) is a calcineurin inhibitor with a narrow therapeutic index that exhibits large interindividual variation. Seventy-eight kidney transplant patients treated with tacrolimus were recruited to study the correlation of dose adjusted trough level (level/dose; L/D) of tacrolimus with CYP3A5 and ABCB1 genotypes, as well as the mRNA copy number of ABCB1 in blood. Patients were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T) and CYP3A5 (G6986A), while ABCB1 mRNA transcript copy number was determined by absolute quantification (real-time PCR) in 46 patients. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus L/D in kidney-transplant patients. Significantly higher L/D was observed among non-expressors (2.85, 95%: 2.05-3.70 (ng·mL(-1))/(mg·kg(-1))) as compared with the expressors (1.15, 95%: 0.95-1.80 (ng·mL(-1))/(mg·kg(-1))) of CYP3A5 (Mann-Whitney U test; P < 0.001). No correlation was observed between L/D and the ABCB1 genotypes. A significant inverse correlation of blood ABCB1 mRNA level with L/D was demonstrated (Spearman's Rank Order correlation; P = 0.016, rs = -0.348). However, in multiple regression analysis, only CYP3A5*3 genotype groups were found to be significantly correlated with tacrolimus L/D (P < 0.001). These findings highlight the importance of CYP3A5*3 pharmacogenotyping among kidney-transplant patients treated with tacrolimus, and confirm the role of blood cell P-glycoprotein in influencing the L/D for tacrolimus.

Matched MeSH terms: Tacrolimus/therapeutic use*
Ointment tacrolimus for steroid resistant adenoviral nummular keratitis

Jamaluddin Ahmad M, Lott PW, Khaliddin N, Singh S

Med J Malaysia, 2020 07;75(4):461-463.
PMID: 32724020

A 33-year-old man presented with a four-day history of redness and blurring of vision of the right eye. A clinical diagnosis of adenoviral keratitis was made with a differential of microsporidia epithelial keratitis. The patient subsequently developed nummular keratitis which was resistant to topical steroids. He continued to develop multiple recurrences of the condition. Treatment with tacrolimus ointment was started as the patient had an elevated intraocular pressure due to prolonged steroid use. Tacrolimus ointment showed a favourable outcome in the management of recurrent nummular keratitis.

Matched MeSH terms: Tacrolimus/therapeutic use*
Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study

de Luca Montes RA, Huq M, Godfrey T, Oon S, Calderone A, Kandane-Rathnayake R, et al.

Adv Rheumatol, 2024 May 08;64(1):38.
PMID: 38720354 DOI: 10.1186/s42358-024-00366-y

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.
METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.
RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.
CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Matched MeSH terms: Tacrolimus/therapeutic use