Riferimento bibliografico
Kawabe A, Nakano K, Kubo S, Asakawa T, Tanaka Y. Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry. Arthritis Res Ther. 2020;22(1):136.
At a glance
The effectiveness of different biological drugs (bDMARDs) for the management of Rheumatoid Arthritis (RA) varies according to the age. Through the analysis of data from the FIRST register, the present study evaluated the retention rates (i.e. persistence in therapy) 3 years after the start of therapy with various biological drugs, showing good results also in patients older than 65 years. Abatacept and tocilizumab might be better candidates for patients older than 75 years.
What is already known
bDMARDs are key options for those RA patients who do not achieve adequate disease control with the standard first line treatment. In these last few years, the use of bDMARDs is increasing in elderly people, although the optimal therapeutic strategy for the use of bDMARDs in elderly RA patients should be better elucidated. More specifically, we have few data about differences about drug effectiveness and safety across age groups.
Design and Method
The authors analyzed data from the FIRST registry, an observational registry designed to assess the effectiveness and safety of bDMARDs in patients with RA. They included in the analysis 1362 patients with RA, older than 20 years, who received a prescription for a bDMARD between Ferbruary 2011 and March 2020. bDMARDs included were: tumor necrosis factor inhibitors (TNFi) (infliximab [IFX], etanercept [ETN], adalimumab [ADA], golimumab [GLM], and certolizumab pegol [CZP]), abatacept (ABA), and tocilizumab (TCZ).
The authors performed a subgroup analysis by dividing the elderly population into age groups of 65–74 years and ≥ 75 years, to compare the effectiveness and safety of bDMARDs among these groups.
The primary outcome was the drug retention rate (duration of treatment until drug discontinuation at the physician’s judgment) in an adjusted data analysis; secondary outcomes included reasons for discontinuation and clinical effectiveness. Reasons for discontinuation were classified into: discontinuation because of remission, insufficient effect, AEs, or others.
Main results
Considering the whole population, the 3-year retention rates (RR) of TNFi, ABA, and TCZ were 43%, 51%, and 65%, respectively. The RR of TCZ was significantly higher than rates of ABA and TNFi.
By grouping for age, the authors reported that:
- In patients aged < 65 years, the 3-year RR of TNFi, ABA, and TCZ were 43%, 47%, and 69%, respectively with a RR of TCZ was significantly higher than rates of ABA and TNFi.
- In patients aged 65–74 years, 3-year RR of TNFi, ABA, and TCZ were 44%, 53%, and 60%, respectively. The retention rate of TCZ was significantly higher than that for TNFi.
- In patients aged ≥ 75 years, 3-year RR for TNFi, ABA, and TCZ were 38%, 63%, and 58%, respectively. The RR of ABA was significantly higher than that of TNFi. No statistical analysis was performed for TCZ usage data because of the small sample size.
- Overall, retention rates of TCZ were higher in patients aged < 65 and 65–74 years, and retention rates of ABA increased with age.
Reasons for the discontinuation of each bDMARD were analyzed by age:
- – In patients aged < 65 years, discontinuation because of remission was more frequent following treatment with TNFi (16.9%) and less frequent following treatment with TCZ (3.4%). The prevalence of effect insufficiency was higher following treatment with ABA (22.0%) and comparable between treatments with TNFi (14.5%) and TCZ (15.5%). AE incidence was lower following treatment with ABA (4.9%).
- In patients aged 65–74 years, discontinuation because of remission was more frequent following treatment with TNFi (10.5%) and the prevalence of effect insufficiency was lower following treatment with TCZ (8.5%). AE incidence was comparable among the three drugs.
- In patients aged ≥ 75 years, discontinuation because of remission was more frequent following treatment with TNFi (9.9%). The prevalence of effect insufficiency was comparable among the three drugs, and AE incidence was lower following treatment with TCZ (6.9%) and ABA (4.3%).
Overall, the rate of discontinuation because of remission was higher following treatment with TNFi, and AE incidence was lower following treatment with ABA in all age groups.
In all patients, the greatest improvement in disease activity measured by using the clinical disease activity index (CDAI) was observed with TNFi treatment; patients aged < 65 years showed the greatest improvement in CDAI following TNFi treatment. Conversely, in the remaining age groups, there were no significant differences in the degree of CDAI improvement following TNFi, ABA, or TCZ treatment.
Limitations
First of all the study has a retrospective design which did not allow to consider all the potential confounders and bias; however, the authors applied a sophisticated statistical method to overcome this issue. A further limitation belongs to the fact that the study is monocentric. The results of this analysis, obtained on a Japanese population can not be automatically extended to other populations. In fact, different RA course and response to treatment may be influenced by genetic background; moreover, the regulatory setting subsiding the prescription of bDMARDs differs among countries potentially afflicting the prescription profile.
What’s new
The present study suggests that the impact of different therapeutical strategies on RA clinical course may be influenced by the age of the patient. Indeed, RR, effectiveness and safety vary among age groups. Thus, age might be an additional clinical parameter to evaluate when allocating a patient to a specific bDMARD.