Liz Lightstone, MBBS, PhD, FRCP, Professor of Renal Medicine for the Faculty of Medicine, Imperial College London, discussed how the potential teratogenic effects of new therapies under investigation for lupus nephritis may hinder clinical trial recruitment for women of childbearing age.
Recruiting clinical trials and determining the efficacy and safety of new 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 in 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 that these women have to use 2 forms of birth control, they can’t get pregnant, etc. We tend to extend the primary endpoint in studies. So 2 years – so you can’t get pregnant for 2 years. You may be in really good remission and you may be 38, so are you really going to college if you have no prospect of getting pregnant? The other thing that naturally happens is they get pregnant and then they’re pregnant on a drug that hasn’t been tested in pregnancy. So I think it’s a real problem.
I understand the caution of a brand new drug; you don’t want to suddenly find out you have a teratogenic drug. But I think we need to be a little more pragmatic, if the preclinical studies really show no reason for any harm. While for MMF [mycophenolate mofetil]we could have predicted based on the previous studies, there was some data that indicated it would be teratogenic.
We predicted that cyclophosphamide would be teratogenic, while I’m not sure if anything like voclosporin [would be]unless it’s so different from the other CNIs [calcineurin inhibitors]. We use them all the time during pregnancy; we use ciclosporin tacrolimus all the time, maybe that will be ok.
And we’re so careful about it that I think you can give women risk-benefit ratios. But I think it’s very difficult, and the demographics you’re dealing with [for] lupus nephritis is women of childbearing age. So I find that the women who are more willing to go in are either very young – that’s kind of hard – and they don’t really think about pregnancy or who have completed their families. And that group in between that you really want to know how the drug works, doesn’t go into a study.