The findings mean it may be feasible to use adult systemic lupus nephritis (SLE) trial data to reduce the data needed for pediatric indications.
Efficacy data from trials of adults with systemic lupus erythematosus (SLE) can be a useful tool to guide pediatric drug development, according to a new report. However, the usefulness of such data will vary from one medication to the next.
Those insights come from a paper recently published in Journal of Clinical Pharmacology.
The authors noted that new drugs are typically tested first in adults and approved for children only after trials in pediatric patients. Although such a system is necessary for ethical and safety reasons, it also means that children have to wait a significant amount of time to receive therapies that have long been available to adults. However, the FDA has shown some flexibility in cases where the adult and pediatric forms of diseases are sufficiently similar, the authors noted. In such cases, the agency can reduce the amount of data it requires for the drugs to be approved in pediatric patients.
They said there is a good opportunity to extrapolate from adult data in the case of SLE, since adults and children have similar disease progression and response to treatment, as well as a similar dose-response relationship, even though pediatric SLE is often more severe. However, they said there has yet to be a systematic attempt to compare treatment responses between children and adults with SLE across different therapeutic classes.
The investigators decided to analyze published exposure-response data and efficacy-vs-time data for 6 SLE drugs—belimumab (Benlysta), mycophenolate (CellCept), mycophenolic acid (Myfortic), rituximab (Rituximab), hydroxychloroquine, azathioprine (Azasan), and cyclophosphamide—to see how the drugs’ performance varied in children compared with adults.
They found that the trial data for belimumab in adults and children were nearly identical in terms of net change in responders at 1 year, and pharmacodynamic modeling suggested mycophenolate had substantially the same exposure and disease activity correlation in both age groups.
There were insufficient data to draw conclusions about the exposure-response relationship for the other 4 drugs. However, the investigators said clinical or pharmacological responses between children and adults were generally similar in published studies.
The authors listed several limitations to their study. They noted that most clinical trials separate results for patients with and without lupus nephritis, but observational studies tend to include both categories of patients. Thus, it was difficult to compare exposure-response relationships across studies. In addition, they said pediatric studies most often involved children who were at or near adolescence, meaning the results may not be generalizable to younger children with SLE.
Despite those limitations, and others, the investigators said their findings should be encouraging because they suggest that adults and children with SLE and lupus nephritis have largely similar responses to therapy.
“Accordingly, adult SLE data should be leveraged to guide the pediatric drug development program and identify areas with residual uncertainty of a drug’s effectiveness or safety in children,” they wrote.
However, they added the caveat that the limits of efficacy extrapolation will vary, and thus the ability to use adult data to curtail clinical trial requirements for pediatric patients will need to be adjusted on a drug-by-drug basis, “depending in part on the drug’s mechanism of action and the similarity in disease manifestations between children and adults.”
Balevic SJ, Niu J, Chen J, et al. Extrapolation of adult efficacy data to pediatric systemic lupus erythematosus. J Clin Pharmacol. Published online August 15, 2022. doi:10.1002/jcph.2139