In many countries, biologics have become the basis for the treatment of a number of immune-mediated diseases, including Crohn's disease, rheumatoid arthritis and psoriasis. Influencing the key components of the immune system, these drugs significantly improve the treatment results of these diseases, effectively control their course and improve the quality of life for patients. At the same time, suppressing certain parts of the immune system leads to the fact that patients are at risk of developing a whole list of serious opportunistic infections; therefore, clinicians should always carefully consider the benefit-risk balance of using this medication before prescribing biological preparations for autoimmune diseases. drug groups.

Tumor necrosis factor alpha (TNF-α, tumor necrosis factor - TNF) is a pro-inflammatory cytokine synthesized by monocytes and macrophages, responsible for many important infection response mechanisms. TNF-α plays a key pathogenic role in the development of autoimmune processes. Currently, there are several TNF-α inhibitors / antagonists on the pharmaceutical market - these are infliximab (remicade, Janssen company), etanercept (Enbrel, Pfizer companies), adalimumab (Humira, AbbVie company), certolizumab pegol (Simzia, company UCB Pharma), golimumab (Simponi, company Janssen). Despite slightly different mechanisms of action, all of these drugs inhibit the binding of TNF-α to this cytokine receptor, thereby preventing the development of pathological inflammation, which underlies the autoimmune processes.

In addition to TNF-α inhibitors, other options for the biological treatment of rheumatoid arthritis and other immuno-mediated diseases are available. Anakinra (Kineret, Sobi), a drug that is a direct cytokine antagonist (interleukin-1), has a mechanism of action similar to TNF-α inhibitors. Abatacept (Orencia, Bristol-Myers Squibb) and rituximab (Rituxan, Genentech / Biogen Idec) work differently - they are included in the cascade of inflammatory responses. Abatacept prevents activation of T cells and rituximab inhibits B cells by specifically binding to the CD20 transmembrane antigen.

According to a meta-analysis that compared the above drugs with a placebo, there was no statistically significant increase in the risk of developing serious infectious complications. However, patients who received high doses of any of the three biological preparations listed above had a higher incidence of infections, and this increase was only statistically significant with anakinra. In addition, when using anakinra at any dose, the greatest risk of developing infections has been noted.

In a recent Cochrane meta-analysis, similar data were obtained that anakinra increases the risk of developing serious infectious complications compared to abatacept and rituximab. In addition, during this meta-analysis, the risk of infections in the context of the use of other TNF-α inhibitors, as well as the interleukin-6 antagonist tocilizumab (Actemra, Genentech ) was compared to placebo (see table). In this meta-analysis, serious infectious complications were defined as infections requiring hospitalization and / or intravenous antimicrobial treatment.

TNF-α plays an important role in protecting against active tuberculosis by activating phagocytosis and killing mycobacteria. In addition, with regard to latent tuberculosis, the growth of mycobacteria is limited by the intracellular granuloma, which is also mainly regulated by TNF-α. Thus, it is expected that the suppression of this cytokine leads to a decrease in the protective properties of the human body compared to active tuberculosis and also increases the risk of latent tuberculosis infection.

Cases of virus reactivation or an increase in the existing viral load with the use of biological preparations have been described, and this is particularly true for viral hepatitis B in patients receiving rituximab, which is most likely associated with role of presenting B-cell antigen. Reactivation of the hepatitis B virus is also possible in patients receiving TNF-α inhibitors, since the functions of TNF-α are to stimulate cell-mediated viral destruction T, and virus replication occurs with the use of TNF-α inhibitors.

Endemic fungal infections, such as histoplasmosis, blastomycosis and coccidioidomycosis, can occur during treatment with TNF-α inhibitors. The mechanisms of development of these infectious complications are similar to those of tuberculosis, namely the suppression of granuloma formation caused by a violation of the cell-mediated immune response. Although screening and possible treatment for mycobacterial and viral infections is recommended before and during treatment with biological drugs, screening for fungal infections is not systematic. In addition, most endemic fungal infections are newly developed, they first appear on the background of treatment with biological drugs and are not the result of the activation of a latent infection.

Other infections can also occur during treatment with biological agents, including those caused by intracellular pathogens such as Legionella pneumophila, Listeria monocytogenes and protozoa of the genus Leishmania. Infections caused by salmonella and viruses, including the herpes zoster virus, have also been reported during treatment with TNF-α inhibitors.

In conclusion, it should be noted that there are few data regarding the assessment of the risks of developing infectious complications during treatment, and they differ between studies. Basically, all chronic infections (e.g., hepatitis B or C virus infection, mycobacterium tuberculosis, latent tuberculosis and other conditions) are exclusion criteria when patients are included in a clinical trial, and there are therefore specific information describing the risk of reactivation of the infection when using most biological preparations simply does not. However, general recommendations for the use of all biological preparations include mandatory screening for relevant infections and, if necessary, the appointment of treatment before using biological agents.