P0669 Safety of intravenous and subcutaneous guselkumab induction administration: Results from the GALAXI and GRAVITI studies in participants with Crohn’s Disease

Abstract Background Guselkumab (GUS) is a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. Induction with both intravenous (IV) and subcutaneous (SC) GUS was effective in phase 2/3 clinical trials of participants (pts) with moderately to severely active Crohn’s disease (CD). To characterize the safety of GUS IV and SC induction regimens, we evaluated safety data from clinical trials of GUS in CD. Methods We evaluated data from phase 2/3 CD studies with IV induction (GUS 200mg IV q4w in GALAXI 1, 2, and 3) and SC induction (GUS 400mg SCq4w in GRAVITI) to assess rates of safety events (proportions of pts with ≥1 event) during the induction period (Week 0-12). Results During the induction period, rates were not higher in either the IV or the SC groups than the respective placebo (PBO) groups for adverse events (AEs), serious AEs, or AEs leading to discontinuation (Table 1). Serious infections occurred in 1 pt in the GUS IV group and 1 pt in the GUS SC group; neither led to discontinuation of study treatment. No serious infections were reported in PBO-treated pts in either group. Of the 1376 GUS SC injections during the induction period in GRAVITI, 6 (0.4%) were associated with injection site reactions, which included pruritus, erythema, and swelling. Injection site reactions beyond the induction period with GUS SC in GALAXI and GRAVITI remained low (≤1%) and were comparable regardless of induction administration route. No cases of active tuberculosis, anaphylaxis, serum sickness reactions, major adverse cardiovascular events, or venous thromboembolism were reported during the induction period. In the IV induction group, 1 opportunistic infection (esophageal candidiasis) was reported in a PBO-treated pt and 2 were reported in GUS-treated pts (cytomegalovirus infection and esophageal candidiasis). In the SC induction group, 1 opportunistic infection of esophageal candidiasis was reported in a PBO-treated pt and 0 were reported in GUS-treated pts. One malignancy (basal cell carcinoma) not leading to discontinuation was reported in a pt in the GUS 400 mg SC group. One death was attributed to a non-suicidal (not self-inflicted) gunshot wound in a pt treated with GUS SC. Clinically significant hepatic disorders were reported in 2 pts in the GUS 200mg IV group (1 SAE and 1 AE that led to discontinuation) and 1 pt in the GUS 400mg SC group (1 AE that led to discontinuation) during the induction period. All cases were confounded by additional diagnoses or concomitant medications. Conclusion Both IV and SC induction demonstrated comparable safety results consistent with the well-characterized GUS safety profile. No new safety concerns were identified.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.