NEWS & PERSPECTIVE
Established efficacy and safety of tacrolimus as an induction treatment for lupus nephritis
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) with high incidence rates in Asians as compared to Caucasians.1 A treatment regimen of cyclophosphamide (CYC) and glucocorticoids (GC) was the standard of care for LN before newer immunosuppressants were developed.2 Although few randomized controlled trials have examined its efficacy and safety, tacrolimus (TAC) has been used as an immunosuppressant for induction therapy in LN.3 The efficacy and safety of TAC as an induction therapy were evaluated in a meta-analysis.3 The results demonstrated increased efficacy in achieving remission when TAC was combined with GC, or mycophenolate mofetil (MMF) and GC, as compared to CYC and GC.3 The results of this meta-analysis were published in Drug Design, Development and Therapy.
SLE is a chronic autoimmune disease characterized by immune complex formation, with multi-organ manifestations.4,5 LN is one of the more severe organ manifestations of SLE, and is a major risk factor for morbidity and mortality among SLE patients due to the progression to end-stage renal disease (ESRD).4,5 LN occurs in up to 60% of patients worldwide, and may be more severe in Asian SLE patients.2
Induction therapy is the initial treatment of active LN, with the principle goal of rapidly attenuating immune-complex mediated renal inflammation and allowing the injured renal parenchyma to heal.6 Traditional induction therapy involves a combination of GC and CYC, which although effective, causes severe adverse effects.2 New immunosuppressants, such as MMF and azathioprine, have emerged as alternatives for LN treatment.2 Although TAC is another immunosuppressant that may be used as induction therapy for LN, few randomized controlled clinical trials have been conducted to interpret its efficacy and safety.3 TAC was thus investigated in a systematic review and meta-analysis, aimed at assessing its efficacy and safety in induction therapy of patients with LN.3
Studies eligible for inclusion in this meta-analysis were randomized controlled trials, open-label prospective studies, case-control studies, observational studies, and cohort studies.3 13 clinical trials were found to be related to TAC for LN – 12 RCTs and one prospective study.3 Outcome measures evaluating the efficacy of TAC included complete remission (CR), total remission (TR; total CR plus partial remission), and proteinuria levels.3 TAC was evaluated in a variety of regimens in the meta-analysis - in combination with GC, and in combination with MMF and GC.3
Patients receiving the TAC + GC regimen were found to have high rates of CR (OR=2.41; 95% CI: 1.46-3.99; p=0.0006) and TR (OR=4.47; 95% CI: 2.24-8.95; p<0.0001) when compared to those receiving CYC + GC.3 The TAC + GC regimen was also shown to be safer than CYC + GC, with lower incidence rates of gastrointestinal syndrome, leukopenia, and irregular menstruation.3
TAC + GC combination was also compared to a regimen of MMF + GC, which found that differences in CR, TR, proteinuria levels, and albumin levels were not statistically significant between the two regimens.3 With regard to the safety, patients receiving TAC + GC saw a lower incidence of herpes zoster or varicella than MMF + GC, but an increased incidence of elevated blood creatinine levels.3 Rates of leukopenia, infection and serious infection saw no statistically significant difference between either regimen.3
When a regimen of TAC + MMF + GC was compared against CYC + GC, a significant difference was observed in the differences of TR (OR=3.32; 95% CI: 2.08-5.32; p<0.00001).3 Notable differences were also observed in urinary protein decline, and rise of serum albumin.3 The TAC + MMF + GC group also showed high CR rates, although they were not statistically significant.3 Similar to the results observed with the TAC + GC regimen, the TAC + MMF + GC regimen also showed lower incidence rates of gastrointestinal syndrome, leukopenia, and irregular menstruation than the CYC + GC regimen.3
The results from this meta-analysis demonstrated TAC to be a safe and efficacious agent for induction therapy in patients with LN.3 Promising recent data have also emerged showing that TAC is preferable to cyclosporine A in the treatment of Asian SLE patients, due to its better tolerability profile.1 However, further research is needed to establish the use of TAC in Asian SLE patients.
- Yap DYH, Chan TM. Lupus Nephritis in Asia: Clinical Features and Management. Kidney Dis (Basel). 2015;1(2):100-109.
- Mok CC, Yap DYH, Navarra SV, et al. Overview of lupus nephritis management guidelines and perspective from Asia. Int J Rheum Dis. 2013;16(6):625-636.
- Zhou T, Lin S, Yang S, Lin W. Efficacy and safety of tacrolimus in induction therapy of patients with lupus nephritis. DDDT. 2019;13:857-869.
- Iwamoto T, Niewold TB. Genetics of Human Lupus Nephritis. Clin Immunol. 2017;185:32-39.
- Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017;12(5):825-835.
- Parikh SV, Rovin BH. Current and Emerging Therapies for Lupus Nephritis. J Am Soc Nephrol. 2016;27(10):2929-2939.
Lupus nephritis: Challenges and gaps in the treatment landscape of Asia
Lupus nephritis (LN) is a manifestation of the systemic lupus erythematosus (SLE). Among SLE patients, around 60% will develop LN, which is a major contributor to morbidity and mortality.1 Compared to Caucasians, Asians have a higher tendency to develop LN.2 In Asia, the severity of LN is higher
Diminished risk of kidney failure in diabetes patients with SGLT2 inhibitors
The increased prevalence of type 2 diabetes mellitus (T2DM) may cause an increase in chronic kidney disease burden.1 Sodium-glucose cotransporter 2 (SGLT2) inhibitors are used to lower blood glucose levels in patients with T2DM,
Transforming treatment in the management of SHPT with etelcalcetide
Secondary hyperparathyroidism (SHPT) is a very common condition in patients with chronic kidney disease (CKD).1,2 Cinacalcet, a calcimimetic that is commonly used to treat patients with SHPT, has been recommended by well-recognized guidelines but appears to have some shortfalls with non-adherence issues.3,4
What not to ignore when diabetes interacts with acute and chronic kidney diseases: A local case sharing
While they may not necessarily have a causal relationship, both chronic kidney disease (CKD) and diabetes mellitus (DM) have become increasingly more prevalent worldwide.1 As these conditions could be risk factors for developing acute kidney injury (AKI),2 CKD and DM must be carefully managed to pre
Belimumab - a well-responded addition for better preservation of renal functions in lupus nephritis
Lupus nephritis is a complication of systemic lupus erythematosus (SLE), an autoimmune disease that induces kidney inflammation and can ultimately lead to end stage renal disease.1,2 Traditionally, the standard treatment for lupus nephritis consists of corticosteroids in combination with intravenous