VIDEO: Relationship between anemia, quality of life in patients with CKD

Editor’s note: This is a previously posted video, and the below is an automatically generated transcript to be used for informational purposes. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

It's a fairly complex relationship. There are a number of observational studies that show fairly consistently, that when you use the KDQOL, the kidney disease quality of life instrument to assess quality of life in patients with chronic kidney disease, their quality of life, primarily in the physical component scores decreases as the hemoglobin goes down. And again, this is fairly consistent across most studies. The emotional component is much more variable. There's probably a little more depression among patients who are anemic, but a lot of the other emotional sub-scores don't seem to be affected. So it's one thing to say, based on observational studies, that low hemoglobin levels are associated with poor quality of life, especially from the physical side. It's another thing to say that treatment of that anemia necessarily improves quality of life. And that has really been the challenge for ESAs over the 31 years since they were first approved by the FDA.

Now in the phase three clinical trials of ESA, there was in fact, the quality of life instrument that was administered pretreatment. So when the patients had their baseline hemoglobin of seven or eight, which was not atypical among dialysis patients in the 1980s before we had ESAs, and they were treated with ESAs, and they got their hemoglobin levels up to 10 or so. And there was no controversy, the quality of life was improved on almost every dimension. Okay, so you say, oh aha. You know, quality of lives improve with ESAs, why isn't that in the label? And I should point out that as of now, there is no quality of life claim in the label for any of the ESAs. And the reason for that is because the FDA changed the rules in then mid 2000s, and basically said, you can't use a pre and post treatment instrument because it may be biased. The patients know that they've gotten the treatment and therefore they may just say they feel better because they expect that the treatment should make them feel better, and not necessarily that there was an objective change in the way they feel. So, no more pre-post instruments. From the mid 2000s on, you had to do a placebo controlled trial.

Well, at that point it was too late to do a placebo controlled trial, and nobody was willing to put patients who have severe anemia on placebo since the standard of care became treatment with ESAs to a hemoglobin of 10 or 11 or 10 to 12. So we've lost the opportunity to convincingly demonstrate with a placebo controlled trial, an improvement of quality of life with the ESAs. However, we do have another chance with this new class of agents that have stabilizers. And as it turns out, several of the phase three clinical trials in non dialysis patients with chronic kidney disease are using placebo controls, and are going to have quality of life instruments associated with those studies. So we will finally have the opportunity to see, based on all of the FDA's requirements, whether or not these newer agents do in fact lead to an improvement in quality of life, as they raise the hemoglobin as compared to placebo double blind controlled patients because the patients will not know whether they got the active drug or not. So that is really going to eliminate the bias that would have otherwise occurred in a pre-post trial. And hopefully, once we have those data, we will be able to see for sure whether or not the improvement in hemoglobin with these newer agents does in fact lead to an improvement in quality of life.