The Use of Biotechnological Drugs in Pediatrics on the Example of Monoclonal Antibodies: Clinical Pharmacology View

The article reviews monoclonal antibodies, its structure, classifications, pharmacodynamics, pharmacokinetics, and adverse effects. There are examples for each section. Approaches to the research and criteria for drug selection in paediatrics are discussed in detail: the role of clinical trials, extrapolation and pharmacometrics. It has been shown that the differences in the pharmacokinetics of monoclonal antibodies between adults and children present due to the age-related characteristics of various physiological processes. The authors analyse such parameters as absorption, bioavailability, distribution, and elimination. The role of monoclonal antibodies immunogenicity in the structure of adverse effects in children is fully presented. Pharmacometrics is reviewed in the form of modelling and simulation in monoclonal antibodies dosing in paediatrics. It is important to consider the growth and development as “moving targets" in pediatrics regardless the principle of monoclonal antibodies dosage in children. The conclusions were made, and the guidelines were prepared based on the article results.

Safety and Impact of Anti-COVID-19 Vaccines in Psoriatic Patients Treated with Biologics: A Real Life Experience

Since all clinical trials conducted during the development of anti-COVID-19 vaccines have adopted among the exclusion criteria the presence of immunodepression or immunomodulating therapy, to date, the effects of vaccination against the new coronavirus 2 in people under such conditions have yet to be clearly defined. The primary objective of the study is to assess the safety of treatment with biotechnological drugs in patients suffering from moderate–severe psoriasis and subjected to the prophylactic vaccination against SARS-Cov-2. Additionally, the secondary objective of the research is to investigate the existence of a possible impact of anti-COVID-19 vaccination on the natural chronic-relapsing course and the severity of the psoriatic disease. The study included 436 patients with moderate–severe psoriasis, both male and female, in treatment with biologics. The data were collected using the direct interview method. A reduction of 74.13% of average Psoriasis Area Severity Index (PASI )compared to baseline (T0) was found in all subjects; this does not differ significantly from the group that underwent vaccination (73.4%). Moreover; at the end of the study, neither mild nor severe adverse events (ADR) were observed among them. In conclusion, biotechnological drugs used in the management of patients with moderate–severe psoriasis demonstrate a high safety profile also in subjects immunized against SARS-Cov-2.

SARS-CoV-2 Infection in Spondyloarthritis Patients Treated With Biotechnological Drugs: A Study on Serology

ObjectiveSerology could help to define the real extent of SARS-CoV-2 diffusion, especially in individuals considered at higher risk of COVID-19, such as spondyloarthritis (SpA) patients undergoing immunosuppressant. Our aim was to detect, by serology, previous SARS-CoV-2 contact in SpA, compared to health care workers (HCW), and healthy controls.MethodsSera from consecutive patients affected by SpA undergoing cytokine-targeted therapy, HCW and healthy controls from 2015 were analysed through chemiluminescent analytical system for the presence of IgG and IgM anti-SARS-CoV-2. Positive patients (IgM or IgG, or both) additionally underwent real-time Polymerase-Chain-Reaction (RT-PCR) to test for active infection. Serology was repeated at 3-months in SpA. Data across 3 groups were compared by Kruskal Wallis/Chi-square, and between 2 groups by Wilcoxon rank test/Chi-Square. P ≤ 0.05 were considered significant.Results200 SpA, 95 HCW and 101 controls were recruited. Positive serology was found in 25(12.5%) SpA, 8(8.4%) HCW, 0(0%) controls (p=0.001). SpA patients with positive serology more frequently reported COVID-19-like symptoms than those with negative serology (20% vs. 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, non severe. No HCW reported symptoms or had positive RT-PCR. In SpA patients, at 3 months, mean IgM titres decreased from 2.76 ± 2.93 to 2.38 ± 2.95 (p=0.001), while IgG titres from 0.89 ± 3.25 to 0.31 ± 0.87 (p=ns).ConclusionsSerology revealed that exposure to SARS-CoV-2 in SpA patients and HCW was higher than expected based on reported symptoms. In SpA, anti-cytokine therapy could act as a protective factor for a severe disease course. However, a seroconversion was not observed at 3-months.

Efficacy of gluten-free diet in patients with rheumatoid arthritis

Recent research has increasingly shown that depending on the foods we eat, gut flora may be affected by an inflammatory or anti-inflammatory response, thus playing an important role in inflammatory autoimmune diseases, such as rheumatoid arthritis or gastroenterological disorders. Gluten seems to be a glycoprotein with a clinically relevant inflammatory effect. Several observational studies and anecdotal cases reported a correlation between gluten and various diseases, including autoimmune diseases, such as rheumatoid arthritis. This study aimed to evaluate whether gluten-free diet could be effective in controlling inflammation and ongoing rheumatoid arthritis symptoms. We report 4 cases of patients with long-standing rheumatoid arthritis with no response to several conventional and biotechnological drugs, treated with a gluten-free diet concurrently with the drug therapy. Our patients presented different degrees of response to the diet, in terms of disease remission and improvement of symptoms. Our cases confirm that a gluten-free diet may improve symptoms of rheumatoid arthritis, even in patients resistant to conventional drug therapies.

Anti-cyclic-citrullinated-protein-antibodies in psoriatic arthritis patients: how autoimmune dysregulation could affect clinical characteristics, retention rate of methotrexate monotherapy and first line biotechnological drug survival. A single center retrospective study.

Aim: Occasional findings of anti-cyclic-citrullinated-protein-antibodies (anti-CCP) were rarely observed in psoriatic arthritis (PsA). The aim of our study is to evaluate whether the presence of anti-CCP can determine different clinical subsets and influence methotrexate monotherapy survival, and biotechnological drug retention rate. Methods: We conducted a retrospective study on PsA patients. All patients were required to fulfill the CASPAR criteria for PsA, and to present juxta-articular osteo-proliferative signs at X-ray. The exclusion criteria were age less than 18 years old, satisfaction of rheumatoid arthritis classification criteria, and seropositivity for rheumatoid factor. Clinical characteristics, anti-CCP titer, drug survival and comorbidities information were recorded for each patient. Statistical significance was set at p ⩽ 0.05. Results: Of 407 patients with PsA screened 113 were recruited. Twelve patients were anti-CCP positive. Methotrexate monotherapy survival was shorter in patients with anti-CCP (150 ± 48.3 weeks versus 535.3 ± 65.3 weeks; p = 0.026) [discontinuation risk hazard ratio (HR) = 2.389, 95% confidence interval (CI) 1.043, 5.473; p = 0.039] than those without. Significant shorter survival of first-line biotechnological drugs (b-DMARDs) was observed in the anti-CCP positive group than in that without (102.05 ± 24.4 weeks versus 271.6 ± 41.7 weeks; p = 0.005) with higher discontinuation risk (HR = 3.230, 95% CI 1.299, 8.028; p = 0.012). A significant higher rate of multi-failure (more than second-line b-DMARDs) was found in anti-CCP positive patients than in those without (50% versus 14%, p = 0.035). Conclusion: Anti-CCP in PsA could be suggestive of more severe disease, with worse drug survival of both methotrexate monotherapy and first-line b-DMARDs, and higher chance to be b-DMARDs multi-failure. So, they can be considered for more intensive clinical management of these patients.