Comparative effectiveness and safety of rituximab vs. subsequent anti TNF therapy in patients with rheumatoid arthritis with prior exposure to anti– TNF therapies

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SCIENCE
Comparative effectiveness and safety of rituximab vs. subsequent anti TNF therapy in patients with rheumatoid arthritis with prior exposure to anti– TNF therapies
Key Take-Away: 

Rituximab related treatment risk was not expected due to differential prescribing patterns favoring one agent vs. another based on adverse events (AEs) associated with the initial anti- tumor necrosis factor (TNF) therapy.

Rheumatoid arthritis (RA) is a chronic, debilitating disease characterized by persistent synovitis and systemic inflammation. RA can cause significant pain, functional disability and decreased quality of life, and increased risk of death. Nonbiologic disease-modifying antirheumatic drugs (nbDMARDs), such as methotrexate (MTX), are the first class of agents used. In patients with active RA despite nbDMARD therapy, treatment guidelines recommend either step-up to combination DMARD therapy or initiation of a biologic agent.

ABSTRACT: 
Background: 

Rheumatoid arthritis (RA) is a chronic, debilitating disease characterized by persistent synovitis and systemic inflammation. RA can cause significant pain, functional disability and decreased quality of life, and increased risk of death. Nonbiologic disease-modifying antirheumatic drugs (nbDMARDs), such as methotrexate (MTX), are the first class of agents used. In patients with active RA despite nbDMARD therapy, treatment guidelines recommend either step-up to combination DMARD therapy or initiation of a biologic agent.

The first choice of biologic therapy is typically an antitumor necrosis factor (anti–TNF) agent. AntiTNF agents have been shown to be effective in improving the signs and symptoms of RA in large randomized controlled trials (RCTs). Patients with active disease despite anti-TNF therapy can subsequently switch to either a different anti-TNF agent or a biologic agent with an alternative mechanism of action (MOA), such as rituximab. Rituximab, a chimeric monoclonal antibody that depletes CD20+ B cells, in combination with MTX has demonstrated sustained efficacy and a well-characterized, long-term safety profile in patients with RA who have had an inadequate response to anti-TNF agents.

Rationale behind research

  • There are limited data available to help physicians decide the effectiveness and safety of non biologics DMARDs and biologics DMARD.

  • Objective: To examine the effectiveness and safety of rituximab versus a subsequent anti-TNF agent in anti-TNF–experienced patients with RA using clinical practice data from the Corrona registry.

Methods: 

  • Study outcomes

    • Primary outcome: The proportion of patients in each group who achieved CDAI LDA or remission (CDAI score ≤10) at 1 year

    • Secondary outcomes: the proportion of patients who achieved modified American College of Rheumatology (mACR) 20/50/70 responses, meaningful improvement in functional status, defined as a decrease of ≥0.25 from baseline in the mHAQ score, at 1 year. New cardiovascular, infectious and cancer events were reported.

  • Time-points

    • Efficacy: Baseline upto 1 year

    • Side effects: Baseline upto 1 year

Results: 

  • Primary outcome

  • In the adjusted logistic regression models, no significant differences were found in the likelihood of achieving LDA or remission between patients in the trimmed population treated with rituximab and those treated with anti-TNF agents (1.35; 95 % CI, 0.95, 1.91)

  • In the stratified-matched population, patients who received rituximab were significantly more likely to achieve LDA or remission (1.54; 95 % CI, 1.00, 2.36)

  • Secondary outcome

  • Rituximab patients were significantly more likely than anti-TNF patients to achieve mACR20/50 and mHAQ improvement in the trimmed population and mACR20 and mHAQ in the stratified-matched population. The rate of new adverse events per 100 patient-years was similar between groups.

Conclusion: 

Patients who switched to rituximab demonstrated a greater benefit in terms of achieving LDA or remission, mACR20/50 response and improvement in physical function, compared with patients who received a subsequent anti-TNF agent.The results of this study reinforce the important observations from European studies that switching to rituximab is superior to receiving another anti-TNF agent, and expand upon these findings with a rigorous evaluation of the comparative safety of these two drug classes, consistent with the Institute of Medicine definition of comparative effectiveness. The growing number of biologic agents indicated for RA, with their myriad mechanisms of action, comparative data are especially important for rheumatologists to guide decision-making to ensure that patients are achieving the best clinical outcomes. There a greater proportion of patients on anti-TNF therapy switched biologic therapies compared to rituximab users, thereby influencing the results; there was no reason to believe that physicians used different criteria for switching.

Finally, safety profiles for the two treatment groups were similar and consistent with what has been previously reported. Future analyses are necessary to better identify which patients are likely to respond to a particular agent based on their response to prior medications.

Arthritis Research & Therapy. 2015 Sep 18; 17(1): 256
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