Baricitinib: efficacy in elderly patients is not limited

Can an advanced age be the reason for withholding targeted therapies from patients with Rheumatoid Arthritis (RA)?

 "Age isn't a contraindication" for rheumatoid arthritis

Can an advanced age be the reason for withholding targeted therapies from patients with Rheumatoid Arthritis (RA)? In no case, the authors of a publication on the efficacy and safety of baricitinib in patients of different age groups believe.

RA can manifest itself at any age. However, prevalence increases with age - and usually, disease activity persists for many years. Often symptoms do not appear until after the age of 60. If older RA patients have to take medication due to comorbidities, these patients can interact with the medication used for RA therapy. Therapeutic decisions are thereby made more difficult. In addition, there is a widespread perception that drugs used to treat rheumatism are less effective in older people than in younger people, and that side effects occur more frequently and are also more severe.

For example, there is evidence from a study that older RA patients discontinue treatment with Biological Disease-Modifying Antirheumatic Drugs (bDMRDs) disproportionately frequently due to side effects. However, this is not confirmed by other studies. According to data from a further analysis, older patients receive less conventional synthetic Disease-Modifying Antirheumatic Drugs(csDMARDs) and may therefore not receive optimal treatment. However, older RA patients are reported to respond as well to methotrexate (MTX) and tumor necrosis factor (TNF) alpha inhibitors plus MTX as younger patients.

Extensive Phase III study program

The potential of RA therapy was expanded in February 2017 with the introduction of the oral selective Janus Kinase Inhibitor (JAK) baricitinib, for which data are available from an extensive Phase III trial program. These included patients with inadequate response to TNF inhibitors (RA-BEACON study), csDMARDs (RA-BUILD) or MTX (RA-BEAM), and csDMARD-naive patients (RA-BEGIN).

In the 24-week RA-BUILD study, 684 patients were randomized 1:1:1 to once daily placebo or baricitinib doses of 2mg or 4mg. In the 52-week RA-BEAM study, 1,305 patients received oral placebo randomized to 3:3:2 once daily, 4mg baricitinib p.o. once daily, or Adalimumab subcutaneous injection every two weeks. Patients in both studies had continued basic therapy with csDMARDs (including MTX).

The primary endpoint of the studies was at least a 20% improvement in symptomatology in the American College of Rheumatology score (ACR20 response) by week 12. Key secondary endpoints were ACR50/70 response, 28 joint disease activity score improvement (DAS28) associated with changes in highly sensitive C-reactive protein (hsCRP; DAS28 hsCRP response), quality of life assessed by HAQ-DI (Health Assessment Questionnaire-Disability Index), and percentage of patients achieving low disease activity (LDA) or complete remissions.

Efficacy comparable in all age groups

In the present post-hoc analysis, the RA-BUILD and RA-BEAM studies were evaluated with regard to the extent to which response and tolerability differ between patients of different age groups. Only data of the 1,989 patients who received placebo (n=716) or 4mg baricitinib (n=714) once daily were included in the pooled evaluation. They were divided into three age groups: <50 years, ≥50 to <65 years and ≥65 years. In the upper age group, 113 patients received placebo and 136 patients received 4mg baricitinib.

Measured by ACR20 response, efficacy was comparable in all three age groups - with a response rate of 69% in baricitinib among <50-year-olds, 66% in the middle age group, and 68% among ≥65-year-olds. In the secondary endpoints, patients in the upper age group also showed no worse response than younger patients.

Side effects, however, led to more frequent discontinuation of the study medication in older patients - regardless of whether they had received baricitinib or placebo. In the verum arm, the abortion rate was 8.8% among ≥65-year-olds compared with 5.6% in the middle and 2.3% in the youngest age group. The incidence of severe side effects was of the same magnitude. Severe infections with baricitinib also occurred numerically more frequently in the 65-year-old patients at ≥ with 2.9% than in the middle age group (0.6%) or in the >50-year-old patients (1.2%).

"Age is not a contraindication for targeted therapies, including baricitinib," conclude the authors of the publication. In view of comorbidities and a possible change in pharmacokinetics, however, older patients with RA should be followed particularly closely.

Fleischmann R, Alam J, Arora V, et al. Safety and efficacy of 
baricitinib in elderly patients with rheumatoid arthritis. RMD Open 2017; 3(2): e000546.