Background Rheumatoid Arthritis is the commonest inflammatory arthritis. Improved understanding of its pathogenesis has led to targeted therapies like TNF inhibitors. With more emphasis on personalised treatment of RA, a better understanding of factors that affect response to treatments is paramount. Obesity has important pharmacokinetic effects on drugs like TNF Inhibitors, while adipose tissue and adipocytokines play an important role in immunomodulation in Rheumatoid Arthritis.1
Objectives In this study, we aim to determine whether Body Mass Index affects the clinical response to anti-TNF drugs in RA patients, and whether there is a difference in clinical response to Infliximab versus other subcutaneously administered anti-TNF drugs in Obese RA patients.
Methods In this retrospective study, we included 145 RA patients on different anti-TNF drugs. Baseline data on demographics, BMI, Rheumatoid Factor (RF), Anti-CCP antibodies (ACPA), DAS28 score, Hospital Anxiety and Depression Scores(HADS), and Health Assessment Questionnaire (HAQ) was collected. A DAS responder status allocated to those with a change in DAS score of 1.2 or above after 6 months of treatment. DAS response was studied for Infliximab group versus the other subcutaneous anti-TNF group. Pearson’s chi-squared test and logistic regression analysis was used for statistical analysis and to build a prediction model of factors associated with response to anti-TNF drugs in RA.
Results We found a poorer response to Infliximab at 6 months in clinically obese RA patients, compared to non-obese individuals in the same group (p value=0.036). However there was no statistical difference in the response rates in the two BMI groups in other anti-TNF group. Multivariate analysis showed that a higher baseline DAS28 score was associated with better DAS response at 6 months (OR= 3.53, p=0.001). Higher baseline Depression score was associated with a poorer response to anti-TNF drugs at 6 months (OR= 0.79, p value= 0.001).
Conclusions Our study provides evidence that high BMI is associated with poorer response to Infliximab at 6 months in RA patients, which is consistent with other recently published data2,3. Higher baseline DAS28 score is associated with better response while high baseline depression score is associated poorer response to anti-TNF drugs at 6 months. The poorer response to Infliximab in clinically obese patients is still poorly understood but may be due to altered pharmacokinetics with increased clearance, greater production of human anti-chimeric antibodies and immunomodulatory role of adipose tissue. However, further studies are required to studythis in larger prospective cohorts with trough drug levels and antibody levels measured in non-responders.
Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nature reviews Immunology. 2006;6(10):772-83. Epub 2006/09/26.
Gremese E, Carletto A, Padovan M, Atzeni F, Raffeiner B, Giardina AR, et al. Obesity reduces the response rate to anti TNFα in rheumatoid arthritis. an approach to a personalized medicine. Arthritis Care & Research. 2012:n/a-n/a.
Klaasen R, Wijbrandts CA, Gerlag DM, Tak PP. Body mass index and clinical response to infliximab in rheumatoid arthritis. Arthritis & Rheumatism.63(2):359-64.
Disclosure of Interest None Declared