Case-Based Review

Rheumatoid Arthritis: Therapeutic Strategies After Inadequate Response to Initial TNF Inhibitor Therapy

Journal of Clinical Outcomes Management. 2019 July;26(4):181-192

References

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How common is discontinuation of the first TNFi?

Several studies have reported that the prevalence of primary failure, secondary failure, and intolerance to TNFis ranges from 30% to 40%.^3-6 Female sex,⁷ concurrent prednisone use,⁸ high disease activity scores,^6,8,9 and the absence of treatment with low-dose methotrexate^7,8 have all been shown to be negative predictors of bDMARD retention and response.¹⁰

Are there any factors that predict TNFi failure?

There are no specific parameters to accurately predict responses to TNFI therapy.¹¹ Several clinical and molecular biomarkers in synovium (initial TNF levels, macrophages, T cells)¹² and peripheral blood (serum myeloid-related protein 8 and 14 complex levels,¹³prealbumin, platelet factor 4, and S100A12)¹⁴ have been described as predictors of clinical response to TNFis, but their utility in clinical practice has not been established and the use of these markers has not yet been incorporated into clinical guidelines.

How is disease activity measured in patients with RA?

In 2010 an international expert consensus panel published treatment recommendations for RA that emphasized a T2T strategy of individualizing and escalating treatment to achieve the lowest disease activity or remission. In clinical practice, numerous tools are available to measure RA disease activity. Herein, we mention several that are most commonly used in clinical practice.

DAS28 combines single activity measures into an overall continuous measure of disease activity and has been endorsed by both the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR). It includes a 28-swollen joint count (SJC), 28-tender joint count (TJC), erythrocyte sedimentation rate (ESR; can also be calculated using C-reactive protein [CRP]), and a patient global assessment (PtGA). The cut-offs used for DAS28 interpretation are as follows: remission (< 2.6), low (≥ 2.6 but ≤ 3.2), moderate (> 3.2 but ≤ 5.1), or high (> 5.1).¹⁵ Some of the difficulties in using DAS28 in daily clinical practice include the need for a lab value and the time needed to perform the joint counts. Note also that due to the inclusion of ESR, which is influenced by age and other factors, DAS28 may underestimate remission in the elderly.

Another measure of RA disease activity is the Simplified Disease Activity Index (SDAI), which includes 28 SJC, 28 TJC, PtGA, provider global assessment (PrGA), and CRP in mg/dL. The level of disease activity using the SDAI is interpreted as: remission (SDAI ≤ 3.3), low (≥ 3.4 but ≤ 11), moderate (> 11 but ≤ 26), or high (> 26). The advantage of the SDAI is that a calculator or computer is not required for calculations. Another measure, the Clinical Disease Activity Index (CDAI), includes a 28 SJC, 28 TJC, PtGA, and PrGA. Because a laboratory value is not needed to calculate the CDAI, it is well-suited for use in clinical practice. When using the CDAI, the level of disease activity can be defined as remission (CDAI ≤ 2.8), low (> 2.8 but ≤ 10), moderate (> 10 but ≤ 22), or high (> 22). Again, as with the SDAI, a calculator or computer is not needed for calculations.