Further analysis of the data from the mice studies, however, showed that the efficacy of blocking OX40L may be limited to a specific small window of time. Together with other data showing enhanced expression of OX40L primarily in patients undergoing asthma exacerbations and a correlation with severe asthma, according to Dr. Croft, this suggests that trials of the efficacy of anti-OX40L therapy should target patients with severe asthma as the main endpoint.
However, he emphasized that blocking one molecule may not work well in many complex diseases and that the temporal understanding of when to deliver treatment for optimal outcome as suggested in the mice studies is too simplistic for human disease.
As such, he pointed to data that show a possible crossover effect of several molecules in the TNF family when working together. For example, a model of asthma showed no therapeutic benefit when only blocking OX40L but significant activity when blocking both OX40L and CD30L. Dr. Croft suggested that this paradigm is likely to translate to other inflammatory and autoimmune diseases where combination therapy may be needed to gain significant therapeutic benefits.
Mary Beth Nierengarten is a freelance medical journalist based in St. Paul, Minn.
Second Chance
If you missed this session, it’s not too late. Catch it on SessionSelect.
References
- Richard AC, Ferdinand JR, Meylan F, et al. The TNF-family cytokine TL1A: From lymphocyte costimulator to disease co-conspirator. J Leukoc Biol. 2015;98:333–345.
- Gauvreau GM, Boulet LP, Cockcroft DW, et al. OX40L blockade and allergen-induced airway responses in subjects with mild asthma. Clin Exp Allergy. 2014;44(1):29–37.
