In phase 3 trials, Upadacitinib ( Rinvoq ), an oral JAK1-selective inhibitor, has been assessed as monotherapy versus Methotrexate ( SELECT-EARLY ) and in combination with Methotrexate versus Adalimumab + Methotrexate ( ADA; SELECT-COMPARE ) in rheumatoid arthritis ( RA ) patients who were Methotrexate-naïve or with inadequate responses to Methotrexate ( MTX-IR ), respectively.
In this analysis researchers have assessed individual and composite measures of disease activity in SELECT-EARLY and SELECT-COMPARE.
In SELECT-EARLY, Methotrexate-naïve patients received Upadacitinib 15 mg or 30 mg monotherapy once daily ( QD ), or Methotrexate monotherapy, for 12 weeks.
In SELECT-COMPARE, MTX-IR patients on stable background Methotrexate received Upadacitinib 15 mg QD, Placebo, or Adalimumab 40 mg every 2 weeks for 12 weeks.
For this analysis, responses at week 12 were defined as greater than or equal to 50% improvement in the 7 components of the ACR response criteria.
Among ACR50 responders, the proportions of patients with greater than or equal to 50% improvement in all 7 components of the ACR criteria was assessed.
The proportion of patients achieving TJC68=0 and SJC66=0 was also determined.
All analyses were based on observed data without imputation.
947 patients were randomized in SELECT-EARLY, and 1629 patients in SELECT-COMPARE. Mean time since rheumatoid arthritis diagnosis was 2.7 years in SELECT-EARLY ( median 6 months ) and 8.2 years in SELECT-COMPARE; mean DAS28 ( CRP ) was 5.9 and 5.8, respectively.
In SELECT-EARLY, significantly more Methotrexate-naïve patients receiving Upadacitinib 15 mg or 30 mg monotherapy achieved greater than or equal to 50% improvements in all ACR components at week 12 compared with Methotrexate.
In SELECT-COMPARE, significantly more MTX-IR patients on Upadacitinib 15 mg + Methotrexate achieved greater than or equal to 50% improvement in the ACR components vs Placebo ( all components) and Adalimubab + Methotrexate ( all components except SJC and PhGA ).
Among patients with ACR50 responses at week 12, approximately half of the Methotrexate-naïve patients on Upadacitinib 15 mg and 30 mg in SELECT-EARLY had greater than or equal to 50% improvements in all 5 remaining ACR components ( pain, PtGA, PhGA, HAQ-DI, hsCRP ) compared with 28% with Methotrexate.
Corresponding proportions in MTX-IR patients in SELECT-COMPARE were 34% for Upadacitinib 15 mg + Methotrexate, 28% for Adalimumab + Methotrexate, and 17% for PBO.
Upadacitinib treatment also significantly increased the proportions of patients achieving both TJC68=0 and SJC66=0 vs PBO or Methotrexate, and SJC66=0 vs Adalimumab + Methotrexate.
In conclusion, in Methotrexate-naïve and MTX-IR patients, treatment responses at 12 weeks occurred in significantly higher proportions of patients receiving Upadacitinib monotherapy versus Methotrexate and Upadacitinib + Methotrexate vs Placebo for all 7 components of the ACR response criteria, and for 5 of 7 ACR components for Upadacitinib + Methotrexate versus Adalimumab + Methotrexate.
Favorable outcomes with Upadacitinib treatment were evident both in composite and individual parameters. ( Xagena )
Source: European League Against Rheumatism ( EULAR ) e-Congress 2020