Safety and effectiveness of baricitinib for rheumatoid arthritis in Japanese clinical practice: 24-week results of all-case post-marketing surveillance

Abstract

Objectives To assess safety and effectiveness of baricitinib treatment for rheumatoid arthritis (RA) in real-world clinical practice. Methods This ongoing all-case post-marketing surveillance study (starting September 2017) includes all patients with RA treated with baricitinib in Japan. Safety and effectiveness (disease activity) were assessed for 24 weeks. Results Safety analyses to February 2021 included 4731 patients (initial baricitinib dose: 4 mg/day, n=3058; 2 mg/day, n=1661; other, n=12); 1059 (22.38%) were ≥75 years, and 3362 (71.06%) previously received biologic therapy. Overall observational period was 1863.14 patient-years; 1174 (24.82%) patients discontinued baricitinib before Week 24, mostly for lack of effectiveness (n=478; 10.10%). Adverse events occurred in 1271 (26.87%) patients (serious: 203 [4.29%]; death: 18 [0.38%]). The incidence of herpes zoster, hepatic function disorder, and serious infection was 3.09%, 2.77%, and 1.90%, respectively. Malignancy occurred in 17 patients (0.36%) and major adverse cardiovascular events in seven patients (0.15%). Among patients with effectiveness data, at least 26.57% (Boolean) achieved remission at Week 24. Conclusions This large nationwide surveillance study evaluated the safety and effectiveness of 24 weeks of baricitinib for RA in real-world clinical practice. Continued surveillance of long-term safety is ongoing.

The RA-BE-REAL Multinational, Prospective, Observational Study in Patients with Rheumatoid Arthritis Receiving Baricitinib, Targeted Synthetic, or Biologic Disease-Modifying Therapies: a 6-Month Interim Analysis

“…This retention rate is aligned with rates reported by real-world studies conducted in Japan. The 6-month retention rate was 86.5% in a Japanese multicenter registry in 113 patients with RA, more than half of whom were previously treated with tsDMARDs [ 18 ], and 75.4% in a post-marketing surveillance study that included 4731 patients with RA treated with baricitinib [ 29 ].…”

A Review of Baricitinib: The Efficacy and Safety in Rheumatic Diseases

“…Looking at the frequency of adverse events in real-world data, adverse events were found to have occurred in 26.87%, whereas serious adverse events occurred in 4.29% of patients during a 24-week follow-up in the Japanese cohort (n=4731). In this cohort, where 54% of the patients were 65 years and older, the frequency of serious infection and HZ were 1.90% and 3.09%, respectively (13). In a database study from Italy, it was observed that within 1 year, 13% of patients discontinued treatment due to side effects and it was emphasized that the frequency of discontinuation due to side effects was higher, especially in elderly patients and in the bDMARD-resistant patient group [hazard ratio (HR) 1.03, 95% CI 1.01-1.06; p=0.008 and HR 1.93 95% CI 1.01-3.67; p=0.045, respectively] (12).…”

“…Additionally, elevated alanine aminotransferase and aspartate aminotransferase levels were detected in 1.9% and 1.3% of baricitinib monotherapy recipients, respectively, and it was reported that these elevations in liver function tests were transient in most cases (2,7). However, hepatic dysfunction with a rate of 2.77% during the 24-week follow-up was also reported in a Japanese cohort (13). During the 24-week follow-up in the RA-BEACON study, side effects were reported in 64% of the placebo group, 71% of the baricitinib 2 mg group, and 77% of the baricitinib 4 mg group.…”

“…It was also reported that 24% of patients discontinued treatment due to ineffectiveness and 13% due to side effects, and that the risk of discontinuation due to ineffectiveness was lower in patients with rheumatoid factor and cyclic citrullinated peptide positivity or bDMARD-naïve patients (12). With real-world data from Japan (n=4731), it was observed that 24.8% of patients stopped taking the drug before week 24 and the reason for discontinuation in most of the cases (10.1%) were reported to be ineffectiveness (13). In a 9.3-year study comparing baricitinib treatment as monotherapy or along with MTX, there was no difference in drug continuation at week 96 between monotherapy (62%) or MTX combination (56%).…”

“…Of the 85 deaths, 22.4% were related to cardiovascular events, 22.4% to infection, 22.4% to malignancy, and 15% to respiratory problems, irrespective of dosage (16). In the Japanese cohort of 4731 patients, mortality was reported to be 0.38% (13). Major cardiovascular events (MACE) were similar in frequency to placebo, and no data baricitinib aggravated heart failure (2).…”