Change Over Time in the Pattern of Clinical Response to First-line Biologic Drugs in Patients with Rheumatoid Arthritis: Observational Data in a Real-life Setting

Background:Long-term observational data on the real-life use of JAK inhibitors (JAKis) for rheumatoid arthritis (RA) and their comparison with biological drugs are still very limited. Large population-based registries have been increasingly used to investigate the performance of targeted drugs in a real-life setting.Objectives:The aim of this study is to evaluate and compare the 3-year retention rate of JAKis, TNF inhibitors (TNFis) and biologic drugs with other mechanisms of action (OMAs) in the large cohort of RA patients included in the Italian national GISEA registry.Methods:Data of all RA patients treated with targeted synthetic or biologic drugs were prospectively collected in the Italian multicentric GISEA registry. The analysis was limited to patients who started a first- or second-line targeted drug in the period after the first JAKi was marketed in Italy (1st December 2017). The 3-year retention rate was calculated by the Kaplan-Meier method and compared between different drug classes by a log-rank test. A descriptive analysis of reasons for discontinuation was performed.Results:The study population included 1027 RA patients (79.8% females, mean age [±SD] 56.9 [±13.5] years, mean disease duration 9.8 [±9] years, mean baseline SDAI 17.5 [±11.9], ACPA positive 67.4%, RF positive 62.7%) who received JAKis (baricitinib or tofacitinib, n=297), TNFis (n=365), or OMAs (n=365) as first or second targeted drug. Main baseline characteristics of study population were overall well balanced between treatment groups. Retention rate was numerically but not statistically higher (p=0.18) in patients treated with JAKis compared with TNFis or OMAs (80.6, 78.9 and 76.4% at 1 year and 73, 56.8 and 63.8% at 3 years, respectively) (Figure 1). Drug survival was significantly higher in patients receiving concomitant methotrexate (MTX) compared with monotherapy only in TNFis (66.8 vs 47.1%, p=0.04) but not in JAKis (76.1 vs 70.1%, p=0.54) and OMAs (66.1 vs 61.9%, p=0.41) group. Therapy was discontinued in a total of 211 patients because of ineffectiveness (n=107), adverse events (n=88), or compliance/other reasons (n=16). The most frequent reason for treatment withdrawal was ineffectiveness in both JAKis (n=30 out of 56) and TNFis (n=45 out of 74) groups, whereas OMAs were discontinued more frequently because of adverse events (n=41 out of 81).Conclusion:Our data confirmed in a real-life setting a favorable 3-year retention rate of all available targeted mechanisms of action for RA therapy. As expected, concomitant MTX significantly impacted persistence on therapy of TNFis only. Discontinuations of JAKis for adverse events were infrequent overall, confirming the safety profile observed in randomized clinical trials.Figure 1.Three-year retention rate by treatment groupDisclosure of Interests:None declared

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The Use of Rheumatic Disease Comorbidity Index for Predicting Clinical Response and Retention Rate in a Cohort of Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Alpha Inhibitors

BioMed Research International ◽

10.1155/2019/6107217 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Martina Biggioggero ◽

Federica Mesina ◽

Ennio Giulio Favalli

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Response ◽

Tumor Necrosis ◽

Retention Rate ◽

First Line ◽

Necrosis Factor Alpha ◽

Comorbidity Index ◽

Factor Alpha ◽

Necrosis Factor ◽

Moderate Response

Introduction. To retrospectively evaluate the impact of comorbidities on treatment choice, 12-month clinical response, and 24-month retention rate in a cohort of patients with rheumatoid arthritis (RA) treated with a first-line tumor necrosis factor alpha inhibitor (TNFi), by using for the first time the Rheumatic Disease Comorbidity Index (RDCI). Methods. The study population was extracted from a local registry of RA patients receiving adalimumab or etanercept as first-line biologics between January 2001 and December 2013. The prevalence of comorbidities was computed, and patients were stratified according to RDCI for evaluating the role of comorbidities on TNFi choice, concomitant methotrexate, clinical response (1-year DAS28-ESR remission and low disease activity [LDA] and EULAR good-moderate response), and the 24-month retention rate. Results. 346 patients (172 adalimumab and 174 etanercept) were included. A significantly higher EULAR good/moderate response (P = 0.020) and DAS28-ESR remission (P = 0.003) were obtained according to RDCI (0, 1, 2, or ≥3). Lower RDCI (P = 0.022), male sex (P = 0.006), higher baseline DAS28-ESR (P = 0.001), ETN (P < 0.001), and concomitant methotrexate (P = 0.016) were predictors of EULAR good/moderate response. Elevated RDCI was a predictor of discontinuation of biologics (P = 0.036), whereas treatment with etanercept (P < 0.001) and methotrexate (P = 0.007) was associated with a lower risk of TNFi withdrawal. Conclusions. Multimorbidity, measured by RDCI, is a negative predictor of TNFi persistence on treatment and of achieving a good clinical response. The use of RDCI may be very useful for identifying patients with RA carrying those comorbid conditions associated with poor prognostic outcomes and for defining new treatment targets in multimorbid RA patients.

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Reliability and Change in Erosion Measurements by High-Resolution peripheral Quantitative Computed Tomography in a Longitudinal Dataset of Rheumatoid Arthritis Patients

The Journal of Rheumatology ◽

10.3899/jrheum.191391 ◽

2020 ◽

pp. jrheum.191391 ◽

Cited By ~ 1

Author(s):

Stephanie Finzel ◽

Sarah L. Manske ◽

Cheryl Barnabe ◽

Andrew J. Burghardt ◽

Hubert Marotte ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Computed Tomography ◽

High Resolution ◽

Intraclass Correlation ◽

Quantitative Computed Tomography ◽

Correlation Coefficients ◽

Peripheral Quantitative Computed Tomography ◽

Good Reliability ◽

Change Over Time ◽

Over Time

Objective The aim of this multi-reader exercise was to assess the reliability and change over time of erosion measurements in rheumatoid arthritis (RA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods HR-pQCT scans of 23 patients with RA were assessed at baseline and 12 months. Four experienced readers examined the dorsal, palmar, radial, and ulnar surfaces of the metacarpal head (MH) and phalangeal base (PB) of the 2nd and 3rd digits, blinded to time order. In total, 368 surfaces (23 patients x16 surfaces) were evaluated per time point to characterize cortical breaks as pathological (erosion) or physiological, and to quantify erosion width and depth. Reliability was evaluated by intraclass correlation coefficients (ICC), percentage agreement, and Light’s kappa; change over time was defined by means ± SD of erosion numbers and dimensions. Results ICCs for the mean measurements of width and depth of the pathological breaks ranged between 0.819 - 0.883, and 0.771 - 0.907 respectively. Most physiological cortical breaks were found at the palmar PB, whereas most pathological cortical breaks were located at the radial MH. There was a significant increase in both the numbers and the dimensions of erosions between baseline and follow-up (p=0.0001 for erosion numbers, width, and depth in axial plane, and p=0.001 for depth in perpendicular plane). Conclusion This exercise confirmed good reliability of HR-pQCT erosion measurements and their ability to detect change over time.

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Biologics registries

Oxford Textbook of Rheumatology ◽

10.1093/med/9780199642489.003.0034_update_002 ◽

2013 ◽

pp. 257-263

Author(s):

David Isenberg ◽

Angela Zink

Keyword(s):

Rheumatoid Arthritis ◽

Life Experience ◽

Real Life ◽

Cancer Development ◽

Controlled Trials ◽

Side Effect Profile ◽

Risk Of Infection ◽

Biologic Drugs ◽

Double Blind

Double-blind controlled trials undertaken over the past two decades have established the short-term effectiveness and side-effect profile of biologic drugs for patients with rheumatoid arthritis and related diseases. However, the development of biologics registers to capture ’real-life experience’ and explore long-term effectiveness and complications is equally important. In this chapter, we demonstrate how these registers have identified long-term joint benefits, a reduction in cardiovascular mortality, reassurance concerning fears about cancer development, and a balanced view of the risk of infection.

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