Efficacy and safety of tacrolimus for induction therapy in patients with active lupus nephritis

• Published in: Modern rheumatology Vol. 21; no. 3; pp. 282 - 289
• Main Authors: Takahashi, Satoshi, Hiromura, Keiju, Sakurai, Noriyuki, Matsumoto, Takayuki, Ikeuchi, Hidekazu, Maeshima, Akito, Kaneko, Yoriaki, Kuroiwa, Takashi, Nojima, Yoshihisa
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.06.2011; Informa Healthcare
• Subjects: Adrenal Cortex Hormones - administration & dosage; Adult; Angiotensin II Type 1 Receptor Blockers - administration & dosage; Clinical trials; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Hypertension, Renal - chemically induced; Hypertension, Renal - drug therapy; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - blood; Immunotherapy; Kidneys; Lupus; Lupus Nephritis - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Original Article; Orthopedics; Proteinuria - drug therapy; Remission Induction; Retrospective Studies; Rheumatoid arthritis; Rheumatology; Tacrolimus - administration & dosage; Tacrolimus - adverse effects; Tacrolimus - blood; Immunosuppressive therapy; Systemic lupus erythematosus; Blood tacrolimus concentration; Lupus nephritis; Tacrolimus
• ISSN: 1439-7595; 1439-7609
• DOI: 10.1007/s10165-010-0398-z

After the completion of a double-blind placebo-controlled trial, tacrolimus (TAC) was approved for the treatment of lupus nephritis (LN) in Japan. However, the approved maximal dose, 3 mg/day, is almost half the dose used for induction therapy outside Japan. In this study, we retrospectively evaluated the efficacy and safety of low-dose TAC (≤3 mg/day) for induction therapy in 13 adult patients (2 men and 11 women) with active LN. Eight patients were treated for LN flares. Twelve patients underwent renal biopsies: 8 with class IV, 2 with class III + V, 1 with class IV + V, and 1 with class V renal histology, according to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. The mean initial doses of prednisone and TAC were 34.6 ± 14.5 and 2.7 ± 0.6 mg/day, respectively. All the patients achieved a complete remission (CR) at 7.7 ± 6.7 months (mean ± SD) after the last administration of TAC, except for 2 patients who discontinued TAC treatment; 1 because of worsening systemic lupus erythematosus and 1 because of hypertension. Two patients experienced a flare-up after achieving CR. The mean blood TAC concentration 12 h after the last administration (C12) was significantly lower among the patients with flare-ups than among those with a sustained CR (1.5 ± 1.5 vs. 5.1 ± 1.9 ng/mL, P  = 0.034). These data showed that low-dose TAC was effective for induction therapy in patients with active LN, although a lower TAC concentration may be associated with a poor outcome.