Case-Based Approach for the Management of Rheumatic Diseases - Episode 4
Transcript: Sergio Schwartzman, MD: So once this patient had had a relatively poor response to ibuprofen and importantly developed GI [gastrointestinal] toxicity to this medication, the decision was made to proceed with therapy with an anti-TNF agent for the management of this patient’s nonradiographic axial spondyloarthritis. The therapy that was chosen is the only approved medication for nonradiographic axial spondyloarthritis in the United States, and that is certolizumab.
Certolizumab is an anti-TNF agent, which is a PEGylated Fab’ fragment and in the study that was done the C-AXSPAND study.
In the C-AXSPAND study, there were only 2 treatment arms. These were patients who were treated with either placebo or certolizumab. A 400-milligram loading dose was utilized and then 200 milligrams every 2 weeks. This was a very robust study, a study in which the primary outcome was, indeed, at 52 weeks, although there were a number of other secondary outcomes that were earlier.
The majority of the patients that entered this study did not respond favorably to a nonsteroidal anti-inflammatory agent—over 80%. Some had been treated with DMARD medications, generally in the 30% range, and corticosteroids were also utilized in about 10% of the patients. Interestingly, and surprisingly—as well as, disappointingly—as many as 10% of the patients in this study had been on narcotics.
The results of this study were striking. The 52-week data, which was the primary outcome, 47% of patients achieved an ASDAS-MI [Ankylosing Spondylitis Disease Activity Score-Major improvement], which was the primary outcome, with only 7% of patients taking placebo achieved that response rate.
There were data earlier on: at 12 weeks, 35% of patients had achieved their response versus 6% of the control group. Such a low number in the control group actually testifies to the fact that this was a very well-done study with a very low placebo response rate.
The implications of the C-AXSPAND study, I think, really have hit 2 high marks. The first is that based on this study, American rheumatologists are now beginning to really understand and conceptualize the concept of nonradiographic axial spondyloarthritis, so there has been an educational component that has been met. And importantly, the fact that we have 1 therapy approved for nonradiographic axial spondyloarthritis means that we now have the capacity to treat this disease from a regulatory perspective.
There is 1 other element that I’d like to cover in terms of certolizumab—it is a unique molecule. As I mentioned previously, this is a pegylated Fab’ fragment, and the advantage of not having an Fc component to this anti-TNF agent is that it does not cross the placenta because placental transfer of antibodies does require an FC portion. So there have been studies that have looked at the transfer of anti-TNF agents across the placenta that have demonstrated that very little certolizumab actually crosses the placenta.
So 1 of the unique features of certolizumab is that in pregnancy, it does not cross the placenta, nor is it expressed in the milk of mothers who nurse their babies.
So a question that is raised is, when should certolizumab be utilized in patients with nonradiographic axial spondyloarthritis, or really across all of its indications, based on this advantage, that it does not cross the placenta? And there isn’t a uniform answer in that, but I think 1 of the issues that is frequently raised by patients is the pregnancy issue. So, both women and men are concerned about therapies during pregnancy. Technically then, though, if we can present a molecule that does not cross the placenta—even in women who are not pregnant but considering pregnancy in the future—women of childbearing age, this would be a potential benefit of this therapy for the management of non-radiographic axial spondyloarthritis and the other groups of diseases.
Transcript Edited for Clarity