Factors affecting the selection of first- and second-line biologic therapy for the treatment of rheumatoid arthritis

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Factors affecting the selection of first- and second-line biologic therapy for the treatment of rheumatoid arthritis
Key Take-Away: 

The present study concluded that age, infectious risk, the number and type of comorbidities, and monotherapy are the main factors affecting the selection of the biologic drug in real life, encouraging the choice towards Abatacept or Tocilizumab compared to TNFi.

Numerous treatments are available for treating rheumatoid arthritis (RA) patients. Biologic DMARDs (bDMARDs) have become the first-line treatment options for those RA patients who do not respond well to conventional DMARDs (cDMARD). 

ABSTRACT: 
Background: 

Numerous treatments are available for treating rheumatoid arthritis (RA) patients. Biologic DMARDs (bDMARDs) have become the first-line treatment options for those RA patients who do not respond well to conventional DMARDs (cDMARD). Several bDMARDs has been licensed for use in rheumatoid arthritis. Among these, Tumor necrosis factor (TNFα) inhibitors are the most significant which are chosen according to different routes, the frequency of administration and unique pharmacokinetic properties. Newer agents like interleukin-6 (IL-6) receptor blocking monoclonal antibody Tocilizumab (TCZ), the T-cell co-stimulation inhibitor Abatacept (ABA), and the anti-CD20 B-cell depleting agent rituximab (RTX) have further increased the therapeutic armory to treat RA.

Despite the wide range and spectrum of bDMARD, there is still limited information known about the first and second line treatment for patients with rheumatoid arthritis. The studies have failed to provide any considerable difference amongst the different classes of bDMARDs regarding efficacy on clinical, functional, and radiographic outcomes. The selection of bDMARD solely relies on the choice of clinician and his/her personal experience.

This study aimed at resolving the issue about best treatment approach for rheumatoid patients by analyzing the factors affecting the choice of bDMARD in a large cohort of RA patients enrolled in LORHEN registry focusing on the prescription of ABA or TCZ compared to TNFis.

Rationale behind research

  • There is limited evidence available on the selection of biological DMARDs as the first-line treatment for rheumatoid arthritis patients.
  • The present study emphasized on exploring the factors affecting the choice of biological DMARDs as the best treatment option in rheumatoid arthritis patients.

Objective

To retrospectively investigate the factors affecting the selection of the first-line bDMARD or the switching strategy in patients with rheumatoid arthritis

Methods: 

 

  • Study outcomes
  • The initial measures were age, LTBI status, HBV OR HCV infections, biomarkers such as seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), DAS score, HAQ score and data regarding treatment as a monotherapy or in combination with cDMARD.
  • The other outcomes were comorbidities related to use of first line and second line bDMARD that were categorized into different organ groups like pulmonary disease, cardiovascular disease, arterial hypertension, dyslipidemia, diabetes mellitus, peripheral neuropathy, osteoporosis, autoimmune thyroid disease, other comorbidities not belonging to the previous categories.
Results: 

 

Outcomes

Baseline characterics: No significant differences were observed between the groups.

Study outcomes:

  • Mean age at the time of first bDMARD initiation and second line treatment was statistically higher for ABA vs TNFi
  • Methotrexate therapy for first line treatment was {ABA=79 (68.70%), TCZ=66 (50.11%), TNFi=655 (64.28%)} and  for second line treatment was {ABA=92 (64.34%), TCZ=53 (54.64%), TNFi=276 (67.98%)} {Figure-1}
  • Methotrexate (MTX) combination therapy was lower in the TCZ group (p = 0.02)
  • Combination therapy with MTX with a second-line bDMARD was prescribed in 54.64% of patients treated with TCZ compared to 67.98% of patients in the TNFi group (p=0.02) and 64.34% of patients on ABA (p = 0.08)

  • The type of comorbidities like dyslipidemia, hypertension, pulmonary disease and the number of comorbidities influenced the choice towards ABA (p=0.01)
  • Multinomial logistic regression demonstrated that a second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi
  • TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA.
Conclusion: 

The introduction of bDMARDs to the standard of care for RA has caused a revolutionary change in the course of the disease. According to the observations made, this is the first study that had demonstrated the influence of higher age and comorbidities on the choice of ABA and TCZ compared to TNFi in a large cohort.

Studies in the past have shown that increasing age is linked to reduced chances of receiving TNFi compared to younger patients, despite higher disease activity levels. The high prevalence of co-morbid conditions in patients with RA has been confirmed by a number of studies, among which, the Comorbidities in Rheumatoid Arthritis (COMORA) study, a large international, cross-sectional study recruiting 4586 patients, has highlighted the high prevalence of comorbidities and related risk factors in patients with RA and the need for an optimization of treatment. 

This study has demonstrated that the number and the type of comorbidity differ among the three different therapeutic agents and may influence the choice of bDMARDs treatment. The first-line biologic agent was preferably ABA vs. TCZ or TNFi in patients with concomitant comorbidities such as dyslipidemia or hypertension. This study demonstrated that in real life, ABA represents the drug of choice in case of underlying infectious risk, such as pre-treatment LTBI positive screening. However, safety data regarding ABA demonstrated that this agent is mainly associated with a lower incidence of serious infections (SI), in general, compared to other bDMARDs.

Sara Monti et al. Clinical Rheumatology (2017) 36(4):753-761

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