Tacrolimus with cyclophosphamide or mycophenolate mofetil boosts renal response in lupus
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Key takeaways:
- Tacrolimus alone had a dose-response relationship with achieving complete renal response in SLE.
- Combination with cyclophosphamide or mycophenolate mofetil was more effective than either drug alone.
Tacrolimus appears to have “synergistic” interactions with mycophenolate mofetil and cyclophosphamide for the treatment of renal involvement in systemic lupus erythematosus, according to observational data published in BMC Rheumatology.
“Multiple clinical studies have shown that a treatment regimen that combines [tacrolimus] with [mycophenolate mofetil] or [cyclophosphamide] has significant renal therapeutic effects on [lupus nephritis] patients who fail to respond to monotherapy,” Siqin Sun, of Nanjing Drum Tower Hospital, in China, and colleagues wrote. “However, the dosage of [tacrolimus] in combination with other drugs remains controversial, and few studies have explored the duration of [tacrolimus] use. Although previous studies involved drug combinations, they rarely assessed the impact of drug synergy on the renal response.”
To further investigate the efficacy of these combinations, Sun and colleagues conducted an observational, retrospective cohort study using patient records from Nanjing Drum Tower Hospital. The study included 793 patients with SLE and renal involvement in the hospital’s rheumatology and immunology departments who were given at least one of the three drugs from January 2010 through December 2021.
Cyclophosphamide or mycophenolate mofetil could be administered sequentially or simultaneously. The researchers compared the levels of complete renal response among 244 patients who initiated tacrolimus, vs. 549 who never started it, using a binary unconditional logistic regression model, while synergistic interactions were assessed using a binary logistic regression model.
According to the researchers, the use of tacrolimus increased the odds of complete response (adjusted OR = 2.82; 95% CI, 1.89-4.22), particularly at a dosage of 4 mg per day or greater (adjusted OR = 5.65; 95% CI, 2.35-13.55) and for longer than 180 days (adjusted OR = 3.6; 95% CI, 2.02-6.41), compared with non-use. The analysis demonstrated a dose-response relationship between complete response and tacrolimus dose and duration (P for both trends < .001), they added.
The analysis also showed synergistic interactions between combination therapy and complete response, with P values of 0.043 for tacrolimus plus cyclophosphamide and 0.025 for tacrolimus plus mycophenolate mofetil.
Compared with cyclophosphamide alone, complete response was more strongly linked to tacrolimus plus cyclophosphamide (adjusted OR = 2.15; 95% CI, 1.15-4.02) and tacrolimus plus mycophenolate mofetil (adjusted OR = 2.43; 95% CI, 1.2-4.92). Mycophenolate mofetil alone demonstrated similar relationships to both combinations. Compared with mycophenolate mofetil alone, the odds were greater with tacrolimus plus cyclophosphamide (adjusted OR = 3.14; 95% IC, 1.49-6.64) and tacrolimus plus mycophenolate mofetil (adjusted OR = 3.54; 95% CI, 1.66-7.58).
“In this cohort study, [tacrolimus] was effective in relieving the condition of SLE patients with a dose-response relationship in the dosage and duration of [tacrolimus] use,” Sun and colleagues wrote. “In addition, [tacrolimus] exhibited relieving efficacy in different subgroups of SLE patients, including SLEDAI score > 12, moderate or severe urinary protein and comorbidities. Compared to monotherapy, [tacrolimus] with [mycophenolate mofetil] or [cyclophosphamide] was positively correlated with a higher [complete response] rate, and a synergistic interaction was observed.”
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