Insensitivity versus poor response to tumour necrosis factor inhibitors in rheumatoid arthritis: a retrospective cohort study

Abstract

Background: With advancement in the treatment options of rheumatoid arthritis (RA), optimising the outcomes of difficult-to-treat patients has become increasingly important in clinical practice. In particular, insensitivity to first-line biologic disease-modifying anti-rheumatic drugs (bDMARD) is becoming a significant problem because it may decrease the treatment adherence of patients. This study aimed to compare RA patients with an insensitivity and those with a poor response to initial treatment with tumour necrosis factor inhibitors (TNFis), which are the most frequently used bDMARDs. Methods: This is a retrospective cohort study using clinical data from the FIRST registry. bDMARD-naïve RA patients treated with tumour necrosis factor inhibitors (TNFis) from August 2003 to May 2019 were included and categorised into three groups: TNFi insensitivity, poor response to TNFis and controls. TNFi insensitivity was defined as follows: (1) discontinuation of TNFi treatment within 22 weeks due to lack of any response, or (2) an increase in the disease activity score in 28 joints-C-reactive protein (DAS28-CRP) of > 0.6 at week 22 compared with week 0. Among the remaining patients, those with a DAS28-CRP > 2.6 at week 22 were categorised in the poor response group. Results: Of the included patients, 94 were classified in the insensitivity, 604 in the poor response and 915 in the control. A higher DAS28-CRP before treatment was a risk factor for a poor response but not for insensitivity. In contrast, dose escalation of infliximab decreased the risk of a poor response but not that of insensitivity. Conclusions: In future research, poor and insensitivity to bDMARDs should be assessed separately to fully elucidate the aetiology of, and risk factors for, bDMARD refractoriness.

Similarity of Response to Biologics Between Elderly-onset Rheumatoid Arthritis (EORA) and Non-EORA Elderly Patients: From the FIRST Registry

“…The latent class analyses also revealed that about one tenth of patients in both the EORA and non-EORA elderly groups showed little response to a b/tsDMARD (Group 3 in Figure 4). This is compatible with our previous study that demonstrated that a difference might exist between insensitivity and poor response to TNFis among b/tsDMARD-naïve patients (21). The results of the present study further suggest that the same might be true for patients treated with other b/tsDMARDs and for patients who are not naïve to b/tsDMARDs.…”

“…We have previously reported that different patterns of treatment response might exist among b/tsDMARD-naïve RA patients treated with TNFis (21). Therefore, we hypothesized that a similar pattern might be observed among the present patients.…”

Metabolomics in rheumatoid arthritis: Advances and review

“…A large proportion of patients show a poor response to DMARDs or biological agents (94,95). Drug treatment can alter serum metabolite levels in RA (96)(97)(98)(99).…”

Preferable Outcome of Janus Kinase Inhibitors For a Group of Difficult-to-Treat Rheumatoid Arthritis Patients: From The FIRST Registry

“…The FIRST registry is a multi-institutional cohort of RA patients treated with b/tsDMARDs, established by the University of Occupational and Environmental Health, Japan and its multiple a liated hospitals. Detail of the cohort is available in other articles [5][6][7][8][9]. In this registry, all registered RA patients were enrolled in a long-term observational study at the point of new or switch-prescription of b/tsDMARDs.…”