OBJECTIVE: The adalimumab biosimilars FKB327 and GP2017 were approved for the therapy of patients with inflammatory bowel disease (IBD). Relatively few prospective studies with biosimilar adalimumab in patients with IBD have been published. The aim of this prospective observational study was to evaluate the effectiveness and safety of the biosimilar adalimumab. MATERIAL AND METHODS: Adalimumab biosimilars FKB327 (Hulio®) and GP2017 (Hyrimoz®) were indicated to 50 naive patients in terms of biological therapy with Crohn's disease (CD) or ulcerative colitis (UC). Effectiveness of therapy was evaluated via the Crohn's Disease Activity Index [CDAI] or the Mayo Scoring System [MSS] in patients with CD or UC, respectively, before and after 12 weeks. Additional goals were to evaluate weight changes, laboratory tests and complications or adverse events of this therapy. RESULTS: In CD patients, remission (CDAI <150) was achieved in 73.5% of cases, partial response (≥70-point decrease in CDAI score from baseline) in 11.8%, no response in 11.8% and 2.9% patients discontinued therapy. In UC patients, remission (total score on partial Mayo index ≤2 points) was achieved only in 18.8% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 43.8%, no response in 25.0% and 12.5% patients discontinued therapy. There were statistically significant improvements in CDAI, MSS, haemoglobin, fecal calprotectin, albumin and CRP serum levels after 12 weeks of therapy. Seven adverse events were identified, three of which resulted in therapy being discontinued. CONCLUSIONS: This prospective observational study proved the effectiveness of the adalimumab biosimilars FKB327 and GP2017 in IBD.

• MeSH
• adalimumab škodlivé účinky   MeSH
• biosimilární léčivé přípravky * škodlivé účinky   MeSH
• Crohnova nemoc * MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• indukce remise MeSH
• lidé MeSH
• prospektivní studie MeSH
• ulcerózní kolitida * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

Úvod: Idiopatické střevní záněty (IBD – inflammatory bowel disease) jsou onemocněním převážně mladého a fertilního věku, kdy i značná část pacientek otěhotní v průběhu nemoci. Jako nejdůležitější faktor zdárného průběhu těhotenství je klidová fáze nemoci, které dosáhneme často intenzivní protizánětlivou léčbou. Vedolizumab (VDZ) a ustekinumab (UST) jsou nové monoklonální protilátky s rozdílným mechanizmem účinku. VDZ je protilátka proti a4ß7 integrinovému receptoru, UST proti interleukinu 12/23 a obě v posledních letech rozšířily spektrum biologické léčby IBD. Cíle: Prezentace výsledků multicentrické observační studie. Primárním cílem našeho sledování bylo posoudit bezpečnost VDZ a UST na průběh gravidity, vývoj plodu a novorozence. Sekundárním cílem bylo zhodnocení transplacentárního přenosu léků prostřednictvím analýzy hladin léků v pupečníkové krvi a žilní krvi matky. Metodika: Multicentrická retrospektivně-prospektivní observační studie. Demografické údaje, informace o charakteru IBD v průběhu těhotenství a detaily terapie byly získávány z preformovaného dotazníku, údaje o porodu a stavu novorozence byly doplněny z porodnické dokumentace. Ke stanovení míry transplacentárního přenosu byly měřeny hladiny VDZ a UST z odběrů pupečníkové krve a žilní krve matky v době porodu pomocí metody ELISA. Výsledky: Od března 2019 do září 2021 bylo do studie zařazeno celkem 85 dokončených gravidit u 79 pacientek z 15 center biologické léčby IBD v České republice, z nichž 36 bylo léčeno VDZ (s mediánem věku žen 32 let) a 49 UST (s mediánem věku žen 30,5 let). Ve skupině s VDZ došlo k porodům živých dětí u 32 gravidit (88,9 %), zaznamenány byly dva časné spontánní aborty a dvě instrumentálně přerušená těhotenství (4; 11,1 %). Celkem 31 dětí (93,9 %) bylo porozeno v termínu, medián porodních hmotností byl 3 097,5 g. V linii s UST bylo porozeno 39 živých dětí (79,6 %), devět těhotenství skončilo časným spontánním abortem a jedno bylo instrumentálně přerušeno (10; 20,4 %). Celkem 38 dětí (97,4 %) bylo narozeno v termínu s mediánem porodních hmotností 3 265 g. Farmakokinetické parametry byly sledovány u 44 párů novorozenec-matka (21 VDZ, 23 UST). Medián hladin VDZ v žilní krvi matky byl 7,2 mg/l, v pupečníkové krvi novorozence 4,7 mg/l (poměr hladin v pupečníku / u matky 0,66), u UST byl medián hladin u matky 4,7 mg/l a novorozence 7,9 mg/l (poměr hladin v pupečníku / u matky 1,65). Závěr: Námi prezentované výsledky pacientek léčených pro IBD a exponovaných v průběhu gravidity minimálně jedné dávce biologické léčby UST nebo VDZ jsou v souladu s dříve publikovanými údaji a potvrzují příznivý bezpečností profil nových biologik v graviditě. Vzhledem ke stále limitovaným počtům zařazených pacientek bude potřeba do budoucna ještě dalšího sledování.

Background: Inflammatory bowel disease (IBD) is mostly diagnosed in young women of fertile age, and a significant number of patients become pregnant while they have the disease. The remission of the illness, which is often achieved by intensive anti inflammatory treatment, has been found to be the most important factor of a successful pregnancy. Vedolizumab (VDZ) and ustekinumab (UST) are newer types of monoclonal antibodies with different mechanisms of effect when compared to anti-TNF treatment. VDZ is a monoclonal antibody against the a4b7 integrin receptor, and UST against interleukin 12/23; both have expanded the spectrum of the biological treatment of IBD in recent years. Aims: To present the results of a multicentre observational study. The primary aim was to assess the safety of vedolizumab and ustekinumab for pregnancy, foetal development and the neonatal outcome. The secondary aim was to measure the drug concentration in maternal and cord blood at the time of delivery. Methods: It was a multicentre, retrospective-prospective observational study. Data on patients’ demographics, clinical characteristics and pregnancy were collected by the treating physician using a predefined questionnaire, data on newborn outcome were obtained from medical documentation. The ELISA method was used to measure the VDZ and UST concentrations. Results: The study took place in 15 IBD clinical centres in the Czech Republic. 79 women with 85 completed pregnancies were included in the study, and they were exposed to VDZ or UST during pregnancy. 36 women were treated with vedolizumab (median age 32 years) and 49 with ustekinumab (median age 30.5 years). In the group with VDZ, live births occurred with 32 women (88.9%), and there were two early spontaneous abortions up to the eighth week of gestation in addition to two instrumentally aborted pregnancies (4, 11.1%). 31 children (93.9%) in the group with VDZ were born at term with a median birth weight of 3,097.5 grams. In the ustekinumab group, 39 women (79.6%) had live births, there were nine early abortions and one instrumentally aborted pregnancy (10, 20.4%). 38 (97.4%) children were born at term with a median birth weight of 3,265 grams. The drug levels of VDZ and UST at birth were measured in 44 neonate-mother pairs (21 VDZ, 23 UST). The median level of VDZ in maternal venous blood was 7.2 mg/l, and in cord blood it was 4.7 mg/l (infant / maternal ratio 0.66). With UST, the median maternal level was 4.7 mg/l, and in neonates it was 7.9 mg/l (infant / maternal ratio 1.65). Conclusion: The results found in a group of women that were being treated for IBD and were exposed to at least one dose of biologic treatment with UST or VDZ during pregnancy are consistent with previously published evidence showing no adverse events, and they confirm the safety profile of new biologics in pregnancy. Due to the still limited number of enrolled patients, further studies are needed on the outcomes of pregnancies with new biologics drugs.

• Klíčová slova
• vedolizumab,
• MeSH
• biologická terapie MeSH
• dospělí MeSH
• humanizované monoklonální protilátky farmakokinetika   terapeutické užití   MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• klinické zkoušky jako téma MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• maternofetální výměna látek MeSH
• mladý dospělý MeSH
• těhotenství * účinky léků   MeSH
• ustekinumab farmakokinetika   terapeutické užití   MeSH
• výsledek těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství * účinky léků   MeSH
• ženské pohlaví MeSH

BACKGROUND AND AIMS: Evidence on the safety of newer biologics during pregnancy is limited. We aimed to assess the safety of ustekinumab and vedolizumab treatment during gestation on pregnancy and infant outcome. Furthermore, we evaluated the placental transfer of these agents. METHODS: We performed a prospective, multicentre, observational study in consecutive women with inflammatory bowel disease exposed to ustekinumab or vedolizumab 2 months prior to conception or during pregnancy. Pregnancy, neonatal, and infant outcomes were evaluated and compared with the anti-tumour necrosis factor [TNF]-exposed control group. Drug levels were assessed in maternal and cord blood at delivery. RESULTS: We included 54 and 39 pregnancies exposed to ustekinumab and vedolizumab, respectively. In the ustekinumab group, 43 [79.9%] resulted in live births, and 11 [20.4%] led to spontaneous abortion. Thirty-five [89.7%] pregnancies on vedolizumab ended in a live birth, two [5.1%] in spontaneous, and two [5.1%] in therapeutic abortion. No significant difference in pregnancy outcome between either the vedolizumab or the ustekinumab group and controls was observed [p >0.05]. Similarly, there was no negative safety signal in the postnatal outcome of exposed children regarding growth, psychomotor development, and risk of allergy/atopy or infectious complications. The median infant-to-maternal ratio of ustekinumab levels was 1.67 and it was 0.59 in vedolizumab. CONCLUSIONS: Use of ustekinumab and vedolizumab in pregnancy seems to be safe, with favuorable pregnancy and postnatal infant outcomes. Placental transfer differed between these two drugs, with ustekinumab having similar and vedolizumab having inverse infant-to-maternal ratio of drug levels compared with anti-TNF preparations.

• MeSH
• gastrointestinální látky škodlivé účinky   terapeutické užití   MeSH
• humanizované monoklonální protilátky * škodlivé účinky   terapeutické užití   MeSH
• idiopatické střevní záněty * farmakoterapie   MeSH
• inhibitory TNF škodlivé účinky   terapeutické užití   MeSH
• kojenec MeSH
• lidé MeSH
• matka - expozice noxám MeSH
• novorozenec MeSH
• placenta MeSH
• prospektivní studie MeSH
• těhotenství MeSH
• ustekinumab * škodlivé účinky   terapeutické užití   MeSH
• výsledek těhotenství MeSH
• výsledek terapie MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Background: Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease. Methods: Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery. Results: Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p = 0.001). Conclusion: Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor (TNF) agents.

• Publikační typ
• časopisecké články MeSH