High-quality evidence shows that alemtuzumab, natalizumab and ocrelizumab present the highest efficacy among DMTs, and other meta-analyses are required regarding adverse events frequency, to better understand the safety of therapies. Based on efficacy profile, guidelines should consider a three-category classification (i.e. high, intermediate and low efficacy).

This chapter aims to describe and review the main important cytokines types (notably interferons), including their biological activities, functions and structures. As a high number of molecules are available, synthesis of the most important cytokines, including tumor factor necrosis, interferons and interleukins will be presented. Here we also describe the relationships between those cytokines with some autoimmune diseases that are promoted by them.

The real-world data showed that the effectiveness of pegvisomant is not as high as reported in interventional studies. Acromegaly appears to be better controlled when pegvisomant is used as a monotherapy. No serious adverse events were associated with the use of pegvisomant; however, given the high cost of this drug, further studies are required.

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SummaryWhat is known and objective: Antifungal prophylaxis is an option to reduce the incidence of invasive fungal infection (IFI) in haematological patients. To date, no network meta-analysis (NMA) of high-quality evidence (double-blind randomized controlled trials) has been performed on this subject. This systematic review and NMA aimed to evaluate the safety and efficacy of different antifungal agents used for prophylaxis of IFI in patients with haematological disorders. Methods:A systematic review was performed according to PRISMA and Cochrane recommendations. The search for articles was conducted on PubMed, Scopus and the Web of Science. We searched for double-blind randomized clinical trials comparing antifungal agents for IFI prophylaxis head-to-head vs placebo in patients with any blood cancer. Network meta-analyses were conducted using Addis version 1.16.6.Evaluation of the quality of included RCTs was also performed.Results: Twenty-five trials were included in the qualitative and quantitative analyses.Posaconazole stood out as the best IFI prophylaxis option and for avoiding IFI-related mortality. For the incidence of candidiasis outcome, the azoles were superior to placebo. Voriconazole and posaconazole were, respectively, the first and second best options. For the incidence of aspergillosis outcome, the probability rank suggested that voriconazole followed by liposomal amphotericin B is, possibly, the best choice.The quality of studies was considered good, with a mean Jadad score of 4.0. What is new and conclusion:The results of our work support prophylaxis with antifungal agents as reducing the risk of IFI in haematological patients. Overall, the secondgeneration azoles were found to be the best option for preventing IFI in this population. K E Y W O R D Santifungal agents, haematologic diseases, invasive fungal infections, network meta-analysis | WHAT IS KNOWN AND OBJECTIVEInvasive fungal infections (IFIs) represent a leading cause of morbidity and mortality in immunocompromised patients, especially those with haematologic malignancies, undergoing haematopoietic stem cell transplantation or with human immunodeficiency virus infection.

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Despite their overall favourable safety profile, tyrosine kinase inhibitors (TKIs) are related to severe adverse events including haematological toxicities such as anaemia, leucopenia, neutropenia and thrombocytopenia. We designed a systematic review and network meta-analysis of randomised controlled trials to compare safety among TKIs (bosutinib, dasatinib, imatinib, nilotinib, ponatinib and radotinib) used by patients diagnosed with chronic myeloid leukaemia. Methods: We obtained data from the PubMed, Scopus, Web of Science, and SciELO databases. The Bayesian approach was used for direct and indirect comparisons, and the treatments were ranked by the surface under the cumulative ranking curve (SUCRA). Results: Seventeen studies were included in the network meta-analysis. Our data show that dasatinib was generally considered worse than the other TKIs, with SUCRA values for 140 mg dasatinib of 90.3% for anaemia, 87.4% for leucopenia, 90.6% for neutropenia and 97.2% for thrombocytopenia. In addition, nilotinib was shown to be safer, with SUCRA values for 600 and 800 mg doses of 21.9 and 35.8% for anaemia, 23.8 and 14.6% for leucopenia, 33.0 and 17.7% for neutropenia, and 28.7 and 32.6% for thrombocytopenia, respectively. Conclusion: Dasatinib appeared as the least safe drug for chronic myeloid leukaemia, probably because it binds to multiple key kinase targets, being more prone to cause serious haematological adverse events. Nilotinib demonstrated a safer profile, mostly due to its selective binding capacity. KEYWORDS chronic myeloid leukaemia, drug-related side effects and adverse reactions, network meta-analysis, tyrosine kinase inhibitors 1 | INTRODUCTION Tyrosine kinase inhibitors (TKIs) represent a milestone in chronic myeloid leukaemia (CML) treatment. Although these drugs are effective and have an overall favourable safety profile with mild to moderate adverse events (AEs), they can also cause severe events including haematological AEs, such as anaemia, leucopenia, neutropenia and thrombocytopenia, which occur due to myelosuppression. Moreover, The authors confirm that the PI for this paper is Roberto Pontarolo and that he had responsibility for this review.

In order to choose the best treatment option, it is necessary to consider the patients' conditions and characteristics. In conclusion, the use of IFN-free therapies meets the high expectations created by clinical trials, including patients in special clinical conditions.