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Comorbidities, older age may influence choice of abatacept
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According to a recently published study, both older age and the presence of comorbidities influence a physician’s choice of abatacept when the other choice is a tumor necrosis factor inhibitor.
“[Our] real-life study demonstrated that age, infectious risk, the number and type of comorbidities and monotherapy are the main factors influencing the choice of the biologic drug in real life, driving the choice toward [abatacept] ABA or [tocilizumab] TCZ compared to [tumor necrosis factor inhibitor] TNFi,” Sara Monti, in the Department of Rheumatology at the University of Pavia in Italy, and colleagues wrote. “The interruption of previous [biologic disease-modifying anti-rheumatic drugs] bDMARDs due to [adverse events] AE influenced the choice toward ABA.”
Monti and colleagues determined which factors influence a physician’s first-line choice or switch strategy of biologics, specifically ABA and TCZ vs. TNFi. The researchers included 1,910 patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry, which began in 2010. The researchers categorized the patient population into first-line (n = 1,264) and second-line bDMARD (n = 646).
The researchers found age was older in the ABA and TCZ groups vs. the TNFi group; methotrexate combination therapy was lower in the TCZ group. They also discovered the type of comorbidity — whether it was dyslipidemia, hypertension or pulmonary disease — and the number of these influenced the choice toward ABA.
In addition, they found TCZ was associated with second-line treatment, older age and more severe disease activity and ABA was associated with second-line treatment, older age, dyslipidemia, pulmonary disease, extra-articular manifestations and cessation of the first bDMARD due to adverse events. In the case of cessation of previous treatment due to AEs, ABA was preferred to TNFi.
“After failing a first-line TNFi, a strategy of swapping to a different [mechanism of action] MoA is usually more common,” the researchers wrote. – by Will Offit
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Stanley Cohen, MD
This manuscript describes the real-life factors that influenced treatment decisions for initial biologic use in rheumatoid arthritis (RA) patients, as well as after first biologic failure in an observational registry from eight centers in Northern Italy focusing on utilization of TNF inhibitors, tocilizumab and abatacept. There is limited randomized clinical trial evidence to suggest a difference in efficacy and safety of biologics, but data from the head-to-head trial (ATTEST) of abatacept/infliximab did suggest lower rate of serious infectious episodes (SIEs) with abatacept and data from long-term extension studies and observational registries have suggested lower SIEs with abatacept and etanercept compared to other biologics.
In this retrospective analysis, most patients initiating biologics received a TNF inhibitor similar to the worldwide experience in which initial use of non-TNF inhibitor biologics is uncommon. However, abatacept was more likely to prescribed in older patients, patients with comorbidities or history of latent tuberculosis. Tocilizumab was used more often as monotherapy. As far as second-line biologic, a switch to a second TNF inhibitor was still the most likely choice but a greater percentage of patients were treated with abatacept or tocilizumab. Patients with adverse events to initial biologics were more likely to receive abatacept, and patients with higher disease activity were more likely to receive tocilizumab.
Tocilizumab has been studied extensively as monotherapy with similar clinical results to combination therapy with methotrexate, although slightly more radiographic progression was seen with monotherapy. Tocilizumab for unclear reasons also seems to induce fewer anti-drug antibodies. Based on this data, the manufacturer of tocilizumab has aggressively marketed this treatment as monotherapy, so the finding of increased use of tocilizumab monotherapy in these clinics is not surprising.
In the ACR recommendations for RA treatment, abatacept is recommended as the biologic of choice in patients with previous SIEs — albeit the level of evidence to support this recommendation is weak. Of interest in this study, the presence of lung disease as a comorbidity resulted in more frequent utilization of abatacept than TNF inhibitors even though the randomized clinical trials suggested increased risk of adverse events and serious infectious episodes in patients with underlying chronic obstructive pulmonary disease and this information is still in the package insert as a warning. Although the evidence for better safety with abatacept is limited, physicians are generally risk adverse and will look for therapies that may be associated with less risk.
This data from these clinics provide a perspective on the clinical decision-making by rheumatologists on choice of initial biologic or second biologic. The results of this observational study are in line with the ACR and EULAR recommendations for RA treatment and it is good to see that clinical rheumatologists adhere to these recommendations. This study did not provide information on patient outcomes which would be helpful to confirm that these choices of therapies were beneficial and that information would be important to confirm the validity of the recommendations.
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