Drug survival of biologics and novel immunomodulators for rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, and psoriasis - A nationwide cohort study from the DANBIO and DERMBIO registries (2022)

Table of Contents
Seminars in Arthritis and Rheumatism Abstract Objective Methods Findings Interpretation Funding Introduction Section snippets Study approvals DANBIO Statistical analysis Results Main findings Author contributions Declaration of interests Acknowledgements/funding sources References (25) Mayo Clin Proc Lancet J. Invest. Dermatol. J. Invest. Dermatol. Biologic fatigue in psoriasis J Dermatolog Treat Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris Br J Dermatol Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR) J Eur Acad Dermatol Venereol Risk of adverse events in psoriasis patients receiving classic systemic drugs and biologics in a 5-year observational study of clinical practice: 2008-2013 results of the Biobadaderm registry J Eur Acad Dermatol Venereol Treatment response and drug retention rates in 24 195 biologic-naive patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration Ann. Rheum. Dis. Comparative Effectiveness of Certolizumab Pegol, Abatacept, and Biosimilar Infliximab in Patients With Rheumatoid Arthritis Treated in Routine Care: observational Data From the Danish DANBIO Registry Emulating a Randomized Trial Arthritis Rheumatol The influence of obesity on response to tumour necrosis factor-alpha inhibitors in psoriatic arthritis: results from the DANBIO and ICEBIO registries Rheumatology Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis Rheumatology Cited by (0) Recommended articles (6)
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Seminars in Arthritis and Rheumatism

Volume 53,

April 2022

, 151979

Abstract

Objective

Drug survival is an important proxy measure for effectiveness of treatments for inflammatory diseases such as rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis. The objective of this study was to examine the real-life drug survival of biologics and novel small-molecule therapies across various disease entities such as RA, AxSpA, PsA, and psoriasis.

Methods

We performed a nationwide cohort study using the prospective nationwide registries DANBIO and DERMBIO, comprising all patients treated with biologics or novel small-molecule therapies for RA, AxSpA, PsA, and psoriasis between January 2015 through May 2021 (DANBIO) and November 2009 to November 2019 (DERMBIO). Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.

Findings

The study comprised a total of 12,089 patients (17,903 treatment series), including 5,104 RA patients (7,867 series), 2,157 AxSpA patients (3,016 series3), 2,551 PsA patients (3,313 series), and 2,577 psoriasis patients (3,707 series). In confounder-adjusted models drug survival in RA was highest for rituximab followed by baricitinib, etanercept and tocilizumab respectively. For AxSpA, drug survival was high for golimumab compared to all other drugs, followed by secukinumab and etanercept and lowest for infliximab. For PsA, tofacitinib and infliximab had the lowest drug survival compared to all other drugs. All other drugs performed almost equally well with a tendency of a somewhat higher drug survival for golimumab, followed by secukinumab and ixekizumab. For psoriasis, drug survival was generally highest for guselkumab.

Interpretation

Differing treatment responses to drugs with various modes of action across RA, AxSpA, PsA and psoriasis emphasize that although these diseases have many overlaps in their pathogenesis, there is a need for an individualized treatment approach that considers the underlying disease, patient profile, and treatment history.

Funding

None

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Introduction

Biological agents have had a profound impact on management of inflammatory joint and skin diseases, which often overlap as exemplified by rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA) and psoriasis [1]. New immunomodulating therapies (e.g., Janus Kinase [JAK] inhibitors) have been developed during the last decade. Simultaneously, indications for their use have expanded markedly.

Studies have shown that immunomodulating therapies may lose their effectiveness after long-term use [2]. The term “drug survival” is used to describe the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice[3]. Previous studies have suggested that for psoriasis, drug survival is better for the interleukin (IL)−12/23 inhibitor ustekinumab, and that this drug has a more favorable safety profile, compared with the tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab [3], [4], [5], [6]. However, real-world data on newer agents such as IL-17, IL-23 and janus kinase (JAK) inhibitors are relatively limited and of short duration and studies have predominantly focused on one inflammatory disease at a time, rather than examining performance across diseases. In inflammatory rheumatic diseases, prior research has predominantly focused on TNF inhibitors [7], [8], [9], and although several other non-TNF therapies are available, these appear so far to be relatively unstudied in a real-world setting [10,11]. Drug survival for secukinumab (an IL-17 inhibitor) appears to be similar to adalimumab (a TNF inhibitor) [10], among patients with PsA, and similar or slightly poorer among patients with AxSpA [11]. However, whether this is also the case for other IL-17 inhibitors, e.g. ixekizumab, or other novel therapies, e.g. JAK inhibitors, remains unclear.

Registry data provides a unique way to study the real-world use of medication. A fundamental limitation of clinical trials is that the included patients differ from patients seen in daily practice, and that between 1–3 out of every four patients in a normal clinical setting would be ineligible to such trials [12], [13], [14]. This emphasizes the need for more robust analyses of real-world data, to further understand the drug profile and treatment patterns. The aim of the study was therefore to examine drug survival among patients with RA, AxSpA, PsA, and psoriasis in a nationwide setting.

Section snippets

Study approvals

The study was approved by the DANBIO (ref. DANBIO-2020–09–18) and DERMBIO (ref. DERMBIO-2020–12–28) steering committees and registered at the Capital Region's inventory (Videnscenter for Dataanmeldelser, ref. P-2019–226). This constitutes the necessary legal requirements, and informed consent is not required per Danish legislation.

DANBIO

DANBIO is a nationwide registry which contains information on Danish patients with inflammatory rheumatic diseases including RA, AxSpA and PsA. Data includes exposure

Statistical analysis

Data in DANBIO and DERMBIO are created as “treatment series”, i.e., sequences of continuous treatment with the same drug. When treatment with one drug is discontinued, a new series may begin when treatment with another drug is prescribed, or if the same drugs as previously used is restarted again. In accordance with previous studies [3,[15], [16], [17]], we combined treatment series if the same drug was used in two consecutive series (i.e., no other drug was started in the meantime) and the

Results

The study comprised a total of 12,089 patients (17,903 treatment series; Table1), including 5104 RA patients (7867 series, Supplementary Table 2), 2157 AxSpA patients (3016 series, Supplementary Table 3), 2551 PsA patients (3313 series, Supplementary Table 4), and 2577 psoriasis patients (3707 series, Supplementary Table 5). The mean (SD) age at first treatment was 57.8 (13.6), 42.3 (13.1), 49 (13.1), and 45 (14.3) years, for RA, AxSpA, PsA, and psoriasis, respectively. Disease-specific time

Main findings

In this nationwide study, we provided comparative drug survival data on 12,089 patients (17,903 treatment series) treated with biologics or novel small molecule immunomodulators for either RA, AxSpA, PsA or psoriasis. In adjusted analyses, rituximab and bariticinib had the best drug survival in treatment of RA, whereas drug survival was highest for golimumab among patients with AxSpA. Golimumab and secukinumab had the highest drug survival in PsA, followed by ixekizumab. For treatment of

Author contributions

All authors had full access to all of data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Egeberg and Dreyer. Acquisition, analysis, and interpretation of data: All authors. Drafting of the manuscript: Egeberg. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Lørup, Rosenø, Aagaard, Nielsen. Obtained funding: None. Administrative, technical, or material

Declaration of interests

Dr. Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and honoraria as consultant and/or speaker from AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers

Acknowledgements/funding sources

We acknowledge the substantial contribution of the academic hospitals and private clinics and their physicians that report data to DANBIO and DERMBIO.

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