Recent Advances in the Pathogenesis and Treatment of Kidney Diseases. Группа авторов
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Название: Recent Advances in the Pathogenesis and Treatment of Kidney Diseases
Автор: Группа авторов
Издательство: Ingram
Жанр: Медицина
Серия: Contributions to Nephrology
isbn: 9783318063509
isbn:
In adults, 2 retrospective analyses described patients with steroid-dependent or frequently relapsing MCNS despite immunosuppressive therapy treated with rituximab [14, 15]. Both case series found an increase in remission in about 60% of patients. We have shown that the first prospective cohort study compared rituximab treatment in 25 patients with steroid-dependent and frequently relapsing MCNS to historical controls and confirmed reduction of relapses in adults with MCNS [16]. As shown in Figure 3, a single dose of rituximab (375 mg/m2; max 500 mg) was administered 4 times every 6 months. For the first 6 months from the first dose of rituximab, the dosage of steroid and immunosuppressants were reduced each month and stopped. Rules for dose reduction of immunosuppressants: steroid reduction by 10 mg every month to discontinuation followed by cyclosporine reduction and discontinuation or Mizoribine reduction and discontinuation. This order can be changed according to the onset of adverse drug effects. A significant reduction in the number of relapses and the total dose and the maintenance dose of steroids administered was observed during the 12-month period after the first rituximab infusion. Complete remission was achieved in all patients undergoing B-cell depletion. A follow-up study to this prospective cohort study showed 8 relapses in 24 months after complete remission compared to 108 episodes in 24 months before rituximab [17]. However, complete remission was maintained in all 20 patients in the rituximab continuation group during the 12-month observation period after the first 4 rituximab infusions. Thus, rituximab may be considered as a radical therapeutic agent for adult patients with MCNS. No RCTs in adults have been conducted comparing rituximab treatment in either frequently relapsing or steroid-dependent patients or as a first-line therapy of MCNS.
Fig. 3. Study protocol of rituximab treatment to reduce the dose of immunosuppressants in steroid-dependent minimal change nephrotic syndrome.
Side Effects of Rituximab Treatment
Rituximab infusion was globally well tolerated. The risk of adverse effects attributed to rituximab varies. With rituximab treatment, the most commonly reported adverse effects are infusion reactions, such as rash and chills; these reactions can be managed by pre-medication or infusion rate adjustments [2]. Each of these reactions is thought to be associated with an underlying disease or to be a result of concomitant immunosuppressive therapy, rather than a direct result of rituximab administration. We have recently assessed the improvement in adverse effects of steroids and the safety of rituximab treatment in adults with steroid-dependent MCNS [18]. A total of 54 adult patients were treated with 4 single-dose 6-monthly infusions of rituximab and the adverse effects with steroids between the first rituximab infusion (baseline) and the end of the 24-month observation period compared. The steroid dose was significantly lower at 24 months than at the baseline. Eight patients with diabetes mellitus showed improved glycemic control at 24 months as compared to that at the baseline. There were no severe adverse effects of rituximab.
Perspectives
Almost all patients whose steroid and other immunosuppressive therapies are withdrawn after rituximab treatment have relapses after the recovery of peripheral B-cell counts. Therefore, further modification of rituximab treatment, including repeated courses of rituximab and adjunct immunosuppressive therapies, may be necessary for maintaining long-term remission. Kimata et al. [19] reported a case series which showed that rituximab administration for 4 times at 3-month intervals induced long-term remission without serious adverse events in children with complicated steroid-dependent MCNS [19]. A case series by Ito et al. [20] suggested that maintenance therapy with mycophenolate mofetil after rituximab administration was effective for maintaining long-term remission in children with complicated frequently relapsing NS/steroid-dependent NS [20]. The efficacy, safety, and cost-effectiveness of various rituximab dosing regimens should be compared to determine an appropriate rituximab treatment regimen for complicated frequently relapsing NS/steroid-dependent NS in adults. Large-scale multicenter cohort studies or multicenter RCTs to compare treatment outcomes after different dosing regimens are required to clarify the optimal dosage of rituximab to use. We have recently shown that treatment with rituximab was possibly superior to previous pharmacological treatments from a health economics perspective [21].
Conclusion
We demonstrated that rituximab treatment was effective and safe in adult patients with steroid-dependent MCNS and dose reduction or discontinuation of the steroid. In addition, rituximab leads to the amelioration of adverse effects of the steroid. Only infusion reactions, such as rash and chills, occurred after single-dose rituximab infusion, and these reactions could be managed by premedication or infusion rate adjustments. Consequently, careful clinical monitoring is mandatory for these patients. The measurement of the peripheral CD19 cell count seems to be a crude monitoring tool, but it is not a reliable means of deciding whether to proceed with rituximab therapy. Controlled randomized trials that include adult patients with steroid-dependent MCNS are required to prove the efficacy and safety of rituximab and to evaluate the cost-effectiveness of rituximab treatment.
References
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