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Systemic Lupus Erythematosus
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Vaneet K. Sandhu, Neha V. Chiruvolu, Daniel J. Wallace
With the advent of newer targeted therapies, the treatment of SLE is shifting from a broad immunosuppressive approach to one that is targeted to specific pathways. Nearly ten years after BEL received FDA approval for SLE, it received a second designation for LN. Voclosporin followed suit for lupus nephritis management, resulting in two FDA designations within twelve months for lupus nephritis alone. The recent approval of anifrolumab for SLE expands our armamentarium further to now include B cell therapy, calcineurin inhibition, and interferon-targeted therapies in addition to the broad immunosuppressants we’ve used for years. With increasing understanding of SLE pathophysiology and the intertwined pathways, the future will likely entail targeting multiple pathways.
Cyclosporine
Published in John Y. M. Koo, Ethan C. Levin, Argentina Leon, Jashin J. Wu, Alice B. Gottlieb, Moderate to Severe Psoriasis, 2014
Ethan C. Levin, Charles N. Ellis
Because the clinical utility of cyclosporine is mitigated by its side effect profile, there is an interest in the use of other systemically administered calcineurin inhibitors that may be safer for patients. Several have been studied, including pimecrolimus, tacrolimus, and voclosporin, formerly ISA247 [139–143]. Studies involving these medications in psoriasis have generally compared them to placebo, rather than to cyclosporine, and have been of relatively short duration (less than a year), limiting the ability to compare their efficacy or side effects head-to-head with cyclosporine. Development of oral pimecrolimus has been stopped. At this writing, there is no current development of oral tacrolimus as a psoriasis therapy, although the drug is available for off-label use in the United States; in limited earlier studies, the drug appeared to have efficacy and side effect profiles similar to oral cyclosporine [142,143]. At the time of this writing, voclosporin development is focused on indications other than psoriasis.
Combination strategies for lupus nephritis: facts and controversies
Published in Expert Review of Clinical Immunology, 2023
There are insufficient data of the safety of novel therapeutic agents during pregnancy. The CNIs such as cyclosporin A and tacrolimus have established safety in LN [112–114]. However, the use of voclosporin in pregnancy is not recommended because there is still a lack of safety data [115]. Although there was so far no increase in the rate of congenital malformations documented with the use of rituximab during pregnancy, risk of B cell depletion and cytopenia in the neonates exists [114]. The EULAR recommends replacement of rituximab with other pregnancy-compatible drugs before pregnancy unless there are no alternatives to control disease activity [114]. Product information of rituximab suggests discontinuation of rituximab for at least 12 months from the last dose before conception because of its long half-life. Likewise, current data are insufficient to establish the safety of belimumab during pregnancy. Cases of congenital malformations and birth defects have been reported with belimumab, but interpretation was confounded by incomplete information, effects of concomitant medications and small number of patients [116]. Belimumab should be replaced by other drugs during pregnancy [114] and discontinuation for at least 4 months is recommended according to the product information. Thus, the conception plan of individual LN patients should be taken into account when choosing newer agents for combination therapies.
Voclosporin: a novel calcineurin inhibitor for the treatment of lupus nephritis
Published in Expert Review of Clinical Pharmacology, 2022
Teun van Gelder, Edgar Lerma, Kory Engelke, Robert B. Huizinga
Voclosporin is a CNI immunosuppressant. By inhibiting the activity of calcineurin, CNIs have two distinct activities in LN: immunomodulatory effects on T-cells and stabilization of the podocyte (Figure 1). In the T-cell, inhibition of calcineurin prevents the translocation of nuclear factor of activated T-cells (NFAT) to the nucleus with the subsequent reduction in the transcription of genes encoding inflammatory cytokines, resulting in the reduction of lymphocyte proliferation and T-cell mediated responses [27,40]. In the podocyte, the inhibition of calcineurin prevents the dephosphorylation of synaptopodin, therefore maintaining the stabilizing function of the cytoskeleton and reducing proteinuria [40,50–53].
Voclosporin: a novel calcineurin inhibitor for the management of lupus nephritis
Published in Expert Review of Clinical Immunology, 2021
Juan M. Mejía-Vilet, Juanita Romero-Díaz
After years of negative clinical trials, voclosporin emerges as a new drug for the management of lupus nephritis and constitutes a potential treatment in the goal to improve kidney survival in patients with lupus nephritis. This drug is now authorized by the US FDA for LN treatment in a combined regimen supported by results from AURA-LV and AURORA-1 trials. Both trials showed efficacy on short-term outcomes, however, there is still caution over the long-term safety and long-term results in preserving kidney function.