Immunosuppressive Tacrolimus Found Safe, Effective for Lupus Nephritis

The immunosuppressive agent tacrolimus, used in combination with other immunosuppressants, was deemed safe and effective for treatment of lupus nephritis, a serious complication of systemic lupus erythematosus (SLE), a new study shows.

The study, “Efficacy and safety of tacrolimus in induction therapy of patients with lupus nephritis,” was published in the journal Drug Design, Development and Therapy.

Lupus nephritis (inflammation of the kidney) is one of the most serious complications of SLE and occurs in up to 60% of patients worldwide. If lupus nephritis goes untreated, the long-term inflammation can cause irreversible damage to the kidney and lead to the development of chronic kidney disease, and eventually renal failure.

Traditional therapy for SLE involves a combination of glucocorticoids (immunosuppressive drugs) with cyclophosphamide (a form of chemotherapy that also suppresses the immune system), both of which improve long-term prognosis. However, doctors are hesitant to prescribe this regimen because of the possibility of severe adverse effects that can include sepsis (generalized infection) and cancer.

Tacrolimus has long been used in kidney transplants, but its safety and efficacy for lupus nephritis have only been assessed in a few randomized controlled clinical trials.

Therefore, researchers in this study set out to conduct a systematic review and meta-analyses to assess the efficacy and safety of tacrolimus as an induction therapy (the first phase of treatment) in patients with lupus nephritis.

First, researchers compared the efficacy of two different types of therapeutic regimens: tacrolimus plus glucocorticoids versus cyclophosphamide plus glucocorticoids.

When looking at these groups, researchers found that patients in the tacrolimus group were more likely to undergo remission and complete remission compared to the cyclophosphamide group.

Albumin is a protein found in blood, but patients with kidney disease normally have high levels of albumin in their urine. Patients in the tacrolimus group had lower albumin levels in their urine and more patients achieved negativity for ds-DNA (a kind of auto-antibodies present at high levels in SLE patients), compared to the cyclophosphamide group.

Furthermore, patients in the tacrolimus group also had lower protein levels in urine (indicative of improved kidney function) as well as lower SLE disease activity. Thus, these results indicate that the tacrolimus regimen is superior to cyclophosphamide in treatment of lupus nephritis.

Next, researchers compared patients who were given tacrolimus plus glucocorticoids or mycophenolate mofetil (another immunosuppressive drug) plus glucocorticoids, but they did not find any significant differences between the two regimens.

Last, they compared a therapeutic regimen of tacrolimus, mycophenolate mofetil, and glucocorticoids, or cyclophosphamide plus glucocorticoids. Investigators found that the triple combination group had more patients achieving remission, complete remission, a decline of protein in urine and a rise of protein in blood compared to the cyclophosphamide group.

Regarding the clinical utility of this finding, the authors explained that the doses used in the triple combination treatment were “much lower than that used for single target therapy, and the adverse reactions may be reduced.”

“[Tacrolimus] is an effective and safe agent in induction therapy of patients with lupus nephritis,” they said.