Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

Abstract

BACKGROUNDOne injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles.METHODSIn this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs).RESULTSFirst, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%).Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued.CONCLUSIONSTreatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity.The trial was registered under ClinicalTrials.gov identifier NCT00696878.

Is there a place for corifollitropin alfa in IVF/ICSI cycles? A systematic review and meta-analysis

“…The optimal corifollitropin dose has been calculated to be 100 mg for women with a body weight %60 kg and 150 mg for women with a body weight >60 kg (8,9) From phase II and III studies it was concluded that a single injection of corifollitropin alfa can replace the first seven injections with standard daily gonadotropins and that stimulation can be continued with daily FSH injections if the need arises (9). This makes corifollitropin alfa potentially more patient-friendly and may lead to a lower dropout rate of patients (10), if safety and effectiveness are first demonstrated. The present review summarizes the evidence from randomized controlled studies (RCTs) on effectiveness, safety, and tolerance of corifollitropin alfa and rFSH, in IVF or ICSI cycles.…”

Efficacy and safety of late-start Corifollitropin-alfa administration for controlled ovarian hyperstimulation in IVF: a cohort, case–control study

“…As far as safety is concerned, the pooled analysis of three large clinical trials (12,13,28) showed that the incidence of severe OHSS was consistent with that expected in the relatively young patient population and was similar for patients receiving CFα (1.8 %) or daily rFSH (1.3 %) (26). In a recent pilot study comparing CFα given on day 2 vs. day 4 in young expected normal responders, the proportion of patients with more than 20 follicles >11 mm diameter the day of ovulation trigger was found to be higher in the day 4 group, raising the suspect that day 4 administration could be associated with a higher risk of OHSS (4).…”

Corifollitropin alfa. Efficacy, safety and convenience for doctor and patient

“…Согласно имеющимся на сегодня данным, до 4 инъекций 15 мкг корифоллитро-пина альфа у мужчин с гипогонадотропным гипогонадиз- Первоначально вероятность иммуногенных реакций на повторные введения корифоллитропина альфа, с учетом молекулярной структуры и степени очистки, оценивалась как незначительная. Однако с целью оценки иммуноген-ности корифоллитропина альфа было проведено крупное открытое многоцентровое клиническое неконтролируе-мое исследование Trust [17]. В исследование было включе-но 30 медицинских центров.…”

“…Все образцы, кроме одного, полученного после 2-го цикла, были отрицатель-ными [17]. В последнем было выявлено значимое усиле-ние связывания (р < 0,05) в антительном тесте, истощае-мое при внесении корифоллитропина альфа и рФСГ, но не ЛГ или ХГЧ.…”

“…Тем не менее в этом образце не было выявле-но нейтрализующей активности или снижения биоактив-ности корифоллитропина альфа. Таким образом, результат не был расценен как клинически значимый [17].…”