PracticeUpdate: Cardiology - Winter 2018

EXPERT OPINION 19

which you can imagine lights are going off in the pharmaceutical companies around the world to follow that up. And if you think about it, canakinumab is the only anti-can- cer therapy that I can think of that not only doesn’t cause cardiovascular harm but actually can provide cardiovascular bene- fit. So this large-scale trial, CANTOS, gave us not only a win for science and a win for our patients but also opened a new win- dow on a potential way to mitigate the risk of cancer. Dr. Caudle: That’s very exciting. Finally, you published recently a paper entitled, Tam- ing Immune and Inflammatory Responses to Treat Atherosclerosis. Can you expand on how the immune system can affect atherosclerosis and the clinical implica- tions of this finding ? Dr. Libby: I spoke to you earlier about those unwelcome invaders to the artery wall – the leukocytes – and canakinumab, the anti-A1 beta therapy really targets an arm of our inflammatory and immune host defense responses, known as innate immu- nity. Innate immunity is pretty blunt but it’s very fast. We don’t have to wait to mobilize it. The particular paper that you are talking about was commenting on an intriguing article about not attacking innate immunity but the other arm of the immune response, adaptive immunity. Adaptive immunity is much more precise and finely tuned than the innate response and it’s the kind of immunity that’s mediated by T lymphocytes and by B lymphocytes by cellular immunity or humoral immunity. And there’s a very strong school of thought that the adaptive immunity may be one of the evildoers in the long, smoldering pro- cess of inflammation of the artery wall. And people are working on ways to target the adaptive arm of the immune response in addition to the innate arm, which we attacked in CANTOS. So this idea of inflam- mation immunity has probably got legs and we won’t…we’re just at the first chapter; we’re just at the beginning of an exciting era when we are learning more about the mechanisms of immune and inflammatory response in cardiovascular disease and finding ways in which we may be able to help our patients by harnessing that knowl- edge.

" There’s a very strong school of thought that the adaptive immunity may be one of the evildoers in the long, smoldering process of inflammation of the artery wall. And people are working on ways to target the adaptive arm of the immune response in addition to the innate arm, which we attacked in CANTOS. "

shown in the JUPITER trial and now in sec- ondary prevention with the canakinumab study but, you know, as my lifelong scien- tific mentor Dr. Bromwell says, ‘there is no free lunch’. So, with this potent anti-inflammatory inter- vention, we did pay a price. We had an increase that was small, but statistically sig- nificant, in fatal infections or sepsis. That was counterbalanced by a remarkable reduction in death due to lung cancer. As a matter of fact, at the highest dose of canaki- numab there was a 77% reduction in deaths due to lung cancer in our trial. Why lung can- cer? Because there is quite an intersection in Venn diagrams between atherosclerosis and lung cancer. With smoking, bronchitis can raise the C-reactive protein. So, we selected for a population that was enriched in people who were at risk for developing lung cancer.

You couldn’t get in the study if you had known cancer, except for basal cell cancer of the skin. So, on the one hand, we paid a price with infection, but I believe that we have enough information from the study with almost 7,000 people treated with this agent to learn what kind of infections and who’s at risk. So I think we’ll be able to mit- igate some of that risk while we won’t be able to eliminate it. I would say that our col- leagues in rheumatology over the last 50 years using anti-inflammatory biologicals have learned how to manage the infec- tion issue quite ably. But also our patients felt better. Their symptoms of arthritis went down, both of osteoarthritis and rheumatoid arthritis and gout fell by more than a half so the anti-inflammatory measure made the patients feel good. And it reduced their cardiovascular risk and it also limited cancer…this is exploratory finding but one

Dr. Caudle is a board- certified Family Medicine physician and Assistant Professor in the Department of Family Medicine at Rowan University-School of Osteopathic Medicine in Stratford, New Jersey.

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VOL. 3 • NO. 3 • 2018