Colchicine in association for phase 3 treatment
The CS influences the patients state of health and it makes the clinical
picture severe. At this stage it is evident that the most important
therapeutic strategy to be implemented is to slow down or block the
uncontrolled inflammatory response.
Antiviral treatments continue to be important even if we remember that
now there is still a big confusion in terms of the greatest effects that
this class of drugs can have. However, since CS has proved to be common
in phase 3, anti-inflammatory therapy can help prevent further
complications, multi-organ dysfunction and patient death.
As we know, there is a variety of anti-inflammatory drugs, including
non-steroidal anti-inflammatory drugs, glucocorticoids,
immunomodulators.
The use of glucocorticoids is still a matter of discussion, in
particular the doses to be used and the time when can be used. In
contrast, the use of cytokine inhibitors such as tocilizumab (IL-6
inhibitor) or anakinra (IL-1 receptor antagonist) has shown good
efficacy, and several studies are underway to test them. However, as
with glucocorticoids, there are still many open questions, when to use
immunomodulators, what doses, to which patients? Only valid clinical
trial protocols can answer these questions. All these questions are
still the subject of intense debate and an uncommon answer in scientific
opinion. The main concern, of course, is that immunomodulatory drugs can
delay the elimination of the virus by the immune system and, worse
still, increase the risk of secondary infections, especially of the
respiratory tract. The biological agents that have shown good efficacy,
and for which several trials are underway, are the inhibitors IL-6
tocilizumab and sarilumab, which are indicated for the treatment of
rheumatoid arthritis. In addition, on August 30, 2017, Tocilizumab was
approved in the United States for life-threatening cytokine release
syndrome caused by chimeric T cell antigen receptor immunotherapy
(CAR-T), and studies are now underway to evaluate its efficacy in the
treatment of FMF and pericarditis, just like colchicine. At this stage
3, it may be useful to administer colchicine (0.5 mg once or twice
daily), in monotherapy or in combination with IL6 inhibitors to control
CS. The advantage of colchicine over IL-6 inhibitors is that it acts
upstream of the cytokine cascade and not only on one cytokine in
particular, it also appears to have a higher safety profile than
immunomodulants and glucocorticoids. In addition, in the most critical
phase a combination of colchicine and IL-6 inhibitors could be
considered, which could show a pharmacological synergism, as shown in
Figure 2. At this stage we could also consider a triple therapy
hydroxychloroquine colchicine and IL-6 inhibitors to block the
inflammatory cascade on multiple points.