ABSTRACT
Background/Aims Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to >=1 biologic disease modifying antirheumatic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study. We aimed to evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECTPsA 2. Methods Pts were randomized to UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatmentemergent adverse events (TEAEs) were summarized for pts who received >=1 dose of study drug using visit-based cut-off at wk 104. Results A total of 641 pts received >=1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks. Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 were consistent with that reported at wk 56. Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and two with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion In PsA pts with prior inadequate response or intolerance to>=1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to two years of treatment. No new safety signals were identified in this long-term extension.
ABSTRACT
L'upadacitinib (UPA), un inhibiteur de Janus kinase (JAK) par voie orale, a démontré son efficacité et sa sécurité chez des patients atteints de rhumatisme psoriasique (RP) ayant une réponse insuffisante ou une intolérance à ≥ 1 traitement de fond biologique (bDMARD) à la S56 de l'étude de phase III SELECT-PsA 2. Évaluer l'efficacité et la tolérance de l'UPA à S104 de l'extension à long terme en cours de l'étude SELECT-PsA 2. Patients randomisés pour recevoir UPA 15 mg, UPA 30 mg ou placebo (PBO) pendant 24 semaines. Les patients sous PBO passaient ensuite à UPA15 ou UPA30. Évaluation d'efficacité à S104 des patients traités en continu par UPA en NRI (imputation en non-répondeurs) et données observées (critères binaires), ou en MMRM (modèle mixte pour mesures répétées) et données observées (critères continus). Au total, 641 patients ont reçu ≥ 1 dose d'UPA. À S104, 38,4 % de l'ensemble des patients avaient arrêté leur traitement par UPA et les taux d'arrêt les plus élevés ont été observés chez les patients randomisés dans le groupe PBO à l'inclusion (total PBO : 46,7 %). Les motifs les plus fréquents d'arrêt du traitement étaient un manque d'efficacité (UPA15 : 12,3 %, UPA30 : 8,7 %, total PBO : 21,7 %) et la survenue d'un EI (UPA15 : 10,9 %, UPA30 : 13,3 %, total PBO : 12,7 %). La proportion de patients sous UPA ayant obtenu une réponse ACR20/50/70, MDA, PASI75/90/100, et résolution des dactylites/enthésites était similaire voire améliorée à S104 de traitement versus S56 (Tableau 1). La variation moyenne par rapport à l'inclusion du HAQ-DI, de l'évaluation de la douleur par le patient et des scores BASDAI/ASDAS était plus importante avec UPA. À S104, les réponses cliniques étaient similaires sous UPA15 et UPA30. Les données de tolérance à S104 (Fig. 1) concordaient avec celles rapportées à S56. Les infections graves, zonas, affections hépatiques, anémies, neutropénies, lymphopénies et élévations des CPK restaient plus élevés sous UPA30 vs UPA15. Les taux de cancers, d'EICM et de TEV étaient similaires dans les 2 groupes UPA. 1 décès rapporté avec UPA15 (inexpliqué, manque d'informations ;la patiente ayant récemment reçu un diagnostic de cancer de l'ovaire) et 2 avec l'UPA30 (pancytopénie et pneumonie à COVID-19). Chez les patients atteints de RP ayant présenté une réponse insuffisante ou une intolérance à ≥ 1 bDMARD, les réponses cliniques se sont maintenues avec UPA15 et UPA30 jusqu'à 2 ans de traitement. Aucun nouveau signal de sécurité n'a été identifié durant cette période d'extension. (French) [ FROM AUTHOR]
ABSTRACT
Background: Upadacitinib (UPA), an oral Janus kinase (JAK) inhibitor, demonstrated efficacy and safety in patients (pts) with psoriatic arthritis (PsA) and prior inadequate response or intolerance to ≥1 biologic disease-modifying antirheu-matic drug (bDMARD) at week (wk) 56 in the phase 3 SELECT-PsA 2 study.1 Objectives: To evaluate the efficacy and safety of UPA at wk 104 from the ongoing long-term extension of SELECT-PsA 2. Methods: Pts were randomized to UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) for 24 wks;PBO pts were then switched to UPA15 or UPA30. For continuous UPA treatment groups, efficacy endpoints at wk 104 were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures (MMRM) and AO (continuous endpoints). Treatment-emergent adverse events (TEAEs) were summarized for pts who received ≥1 dose of study drug using visit-based cut-off at wk 104. Results: A total of 641 pts received ≥1 dose of study drug. At wk 104, 38.4% of all patients had discontinued study drug, with the highest discontinuation observed in patients randomized to PBO at baseline (all PBO: 46.7%). The most common reasons for discontinuation were lack of efficacy (UPA15: 12.3%, UPA30: 8.7%, all PBO: 21.7%) and adverse event (UPA15: 10.9%, UPA30: 13.3%, all PBO: 12.7%). The proportion of UPA pts that achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of dactylitis and enthesitis were generally similar, or further improved, with 104 wks of treatment vs 56 wks1 (Table 1). Similarly, mean change from baseline in HAQ-DI, patient's assessment of pain, BASDAI, and ASDAS was improved with UPA treatment. At 104 wks of therapy, clinical responses were largely similar with UPA15 and UPA30. Generally, safety data at wk 104 (Figure 1) were consistent with that reported at wk 56.1 Rates of serious infection, herpes zoster, hepatic disorder, anemia, neutropenia, lymphopenia, and CPK elevation remained numerically higher with UPA30 vs UPA15, while rates of malignancies, MACE, and VTE were similar for both UPA groups. One death was reported with UPA15 (unexplained due to lack of information;however, the patient had recently been diagnosed with ovarian cancer) and 2 with UPA30 (pancytopenia and COVID-19 pneumonia). Conclusion: In PsA pts with prior inadequate response or intolerance to ≥1 bDMARD, clinical responses were maintained with UPA15 and UPA30 up to 2 years of treatment. No new safety signals were identifed in this long-term extension.