Subscribe

Upadacitinib Is Effective in Patients with Active RA with Inadequate Response to Conventional Synthetic DMARDs

Rheumatology Practice Management December 2017 Vol 5 No 6 - ACR 2017 Conference Correspondent, Rheumatoid Arthritis

Upadacitinib is an oral selective JAK-1 inhibitor that is being clinically investigated for the treatment of patients with moderate-to-severe rheumatoid arthritis (RA). This is an analysis of the double-blind, placebo-controlled period 1 of the randomized phase 3 study that evaluated upadacitinib in patients with inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).

During the double-blind, placebo-controlled period 1 of the SELECT-NEXT study, patients were randomized 1:1:1 to receive the once-daily, extended-release formulation of upadaci­tinib at 15 mg or 30 mg, or placebo for 12 weeks. Period 2 of the study (a blinded extension for 5 years) was not included in the analysis. The 2 parallel primary efficacy end points were the proportion of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) response and Disease Activity Score 28–C-reactive protein (DAS28-CRP) low disease activity (LDA; ≤3.2) at week 12; secondary outcomes included ACR20 at week 1, 50% improvement in ACR criteria (ACR50), 70% improvement in ACR criteria (ACR70), DAS28-CRP <2.6, Clinical Disease Activity Index (CDAI)-LDA (≤10), change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), 36-Item Short Form Survey (SF-36), morning stiffness duration, and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).

Of the 661 patients who received the study drug, 618 (93.5%) completed period 1 of the study and were included in the analysis (upadacitinib 15 mg, 221; upadacitinib 30 mg, 219; placebo, 221). Baseline patient and disease characteristics were similar across the treatment arms. In terms of the 2 primary end points, a significantly higher proportion of patients treated with upadacitinib 15 mg and 30 mg once daily achieved an ACR20 response at week 12 (64% and 66%, respectively, vs 36%; P <.001) and DAS28-CRP LDA (48% and 48%, respectively, vs 17%; P <.001) compared with placebo. Notably, a significantly higher proportion of upadacitinib-treated patients achieved ACR50 (upadacitinib 15 mg, 38%; upadacitinib 30 mg, 43%; placebo, 15%) and ACR70 responses (upadacitinib 15 mg, 21%; upadacitinib 30 mg, 27%; placebo, 6%) in the 15-mg and 30-mg once-daily arms (43.4% and 26.5%, respectively) compared with placebo. Moreover, a significantly higher proportion of upadacitinib-treated patients achieved clinical remission at week 12, as assessed by DAS28-CRP <2.6 (15 mg, 31%; 30 mg, 28%; placebo, 10%; P <.001) and CDAI-LDA (15 mg, 40.3%; 30 mg, 42%; placebo, 19%; P <.001) versus placebo. Notably, significant improvements were observed by week 1 of treatment. Patients treated with upadacitinib at both doses also experienced significantly greater improvements in DAS28-CRP, HAQ-DI, SF-36, pain, Patient Global Assessment, morning stiffness, and FACIT-F versus placebo (P <.001).

Safety analysis showed a numerically higher incidence of adverse events (AEs; upadacitinib 15 mg, 56.6%; upadacitinib 30 mg, 53.9%; placebo, 48.9%) and serious AEs (upadacitinib 15 mg, 4.1%; upadacitinib 30 mg, 2.7%; placebo, 2.3%) with upadacitinib versus placebo. The most frequently reported AEs (>3%) included nasopharyngitis, upper respiratory infection, headache, cough, nausea, and diarrhea. Although the overall incidence of infection was higher in the upadacitinib 15-mg (29.0%) and 30-mg (31.5%) cohorts versus placebo (21.3%), incidence of serious infections was low (0.5% and 1.4%, respectively). Three cases of herpes zoster/varicella zoster virus infection were reported in the active arm (2 in the 30-mg cohort, 1 in the placebo cohort). In the upadacitinib cohorts, 2 malignancies, including nonmelanoma skin cancer, and 3 adjudicated cardiovascular events were reported. No deaths or cases of tuberculosis or gastrointestinal perforations were reported, and incidence of hematologic toxicities was low.

In conclusion, the study met all primary and key secondary end points to demonstrate that upadacitinib 15 mg and 30 mg once daily with background csDMARDs was associated with significant improvement in disease activity and functional outcomes in this patient population with RA and inadequate response to csDMARDs compared with placebo.

Source: Burmester GR, Kremer J, van Den Bosch F, et al. A phase 3 randomized, placebo-controlled, double-blind study of upadacitinib (ABT-494), a selective JAK-1 inhibitor, in patients with active rheumatoid arthritis with inadequate response to conventional synthetic dmards. Arthritis Rheumatol. 2017;69(suppl 10). Abstract 1904.

Related Items
Infliximab Biosimilar Only Moderately Less Expensive Than Reference Drug Under Medicare Part D
Clark Westfield
Rheumatology Practice Management October 2018 Vol 6 No 5 published on October 25, 2018 in Rheumatoid Arthritis
Efficacy and Safety of Switching from Adalimumab to Sarilumab
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Sustained Response in TARGET Study of Sarilumab + csDMARDs versus Placebo in RA Patients with Inadequate Response to TNF Inhibitors
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Highly Sensitive Cardiac Troponin I Levels in Peripheral Blood Predict CV Events in Patients with RA
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Sarilumab + csDMARDs Effective Regardless of Baseline Disease Activity in RA Patients with Inadequate Response to TNF Inhibitors
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
An Updated Integrated Safety Analysis of Baricitinib for the Treatment of Moderate-to-Severe RA
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Cost per Response for Abatacept versus Adalimumab in Patients with Seropositive, Erosive Early RA
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Sarilumab Efficacy Maintained or Improved in Previously Treated Patients with RA
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Long-Term Efficacy and Safety Results of SIRROUND-D Trial of Sirukumab in Patients with Active RA Despite DMARD Treatment
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Longer Duration of Response in MOBILITY Study with Sarilumab plus MTX in Patients with Active, Moderate-to-Severe RA
Rheumatology Practice Management December 2017 Vol 5 No 6 published on January 8, 2018 in ACR 2017 Conference Correspondent, Rheumatoid Arthritis
Last modified: January 11, 2018
  • American Health and Drug Benefits
  • Lynx CME
  • Value Based Care in Rheumatology
  • Oncology Practice Management
  • Urology Practice Management

Search