Liz Lightstone, MBBS, PhD, FRCP, professor of renal medicine for the Faculty of Medicine, Imperial College London, discussed how the potential teratogenic effects of novel therapies being investigated for lupus nephritis can impede clinical trial recruitment for women of childbearing age.
Clinical trial recruitment and determining the efficacy and safety of novel therapies for lupus nephritis in women of childbearing age are challenging, as the risk of pregnancy and potential teratogenic effects of these drugs are not well established, said Liz Lightstone, MBBS, PhD, FRCP, professor of renal medicine for the Faculty of Medicine, Imperial College London.
Can you discuss the challenge of pregnancy for women with lupus nephritis participating in clinical trials?
So, it's really hard, because all the studies say these women have got to use 2 forms of contraception, they can't get pregnant, etc. We're tending in trials to elongate the primary endpoint. So, 2 years—so you cannot get pregnant for 2 years. You might be in a very good remission and you might be 38, so are you really going to go into a study when you have no prospect of being allowed to get pregnant? Of course, the other thing that happens is they do get pregnant and then they're pregnant on a drug that's not tested in pregnancy. So, I think it's a real issue.
I understand the caution of a brand new drug; you don't want to suddenly find you've got a teratogenic drug. But I think we need to be a little bit more pragmatic, if the preclinical studies really show no reason for any damage. Whereas for MMF [mycophenolate mofetil], we could have predicted from the studies that went before, there were some data to suggest it was going to be teratogenic.
Cyclophosphamide we predicted would be teratogenic, whereas I'm not sure something like voclosporin [would be], unless it's so different from the other CNIs [calcineurin inhibitors]. We use them in pregnancy all the time; we use cyclosporine tacrolimus all the time, perhaps that will be fine.
And we're so cautious about it where I think you can give women risk-benefit ratios. But I think it's very hard, and the demographic you're treating [for] lupus nephritis is women of childbearing age. So, I find the women who are more willing to go in are either very young—that's quite difficult—and who are not really contemplating pregnancy or who've completed their families. And that group in between who you really want to know how the drug works won't go into a study.