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Seminars in Arthritis and Rheumatism
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.
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.
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.
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.
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 . 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 . 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. 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 , , , . 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 , , , 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) , among patients with PsA, and similar or slightly poorer among patients with AxSpA . 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 , , . 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.
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 is a nationwide registry which contains information on Danish patients with inflammatory rheumatic diseases including RA, AxSpA and PsA. Data includes exposure
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,, , ], 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
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
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
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
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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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
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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
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Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis
Research articleVariations in Takayasu arteritis characteristics in a cohort of patients with different racial backgrounds
Seminars in Arthritis and Rheumatism, Volume 53, 2022, Article 151971
We aimed to describe differences in disease characteristics and outcomes in Takayasu arteritis (TA) patients with different racial backgrounds.
This was a retrospective cohort study consisting of TA patients seen at specialty vasculitis clinics from five academic hospitals across Canada. Disease features, treatments and outcomes were compared between White and non-White patients.See AlsoAbstracts zum 40. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh) - PDF Free DownloadL5-S1 Disc Bulge, Slip Disc, Stenosis & SpondylolisthesisBest Golf Grips For Arthritic Hands in 2022
The cohort included 113 patients, of which 51 were White. Over 50% of the non-White patients were Asian. Compared to non-White patients, White patients had higher CRP and ESR at diagnosis (33.6mg/l versus 9.4mg/l, p=0.033; and 51mm/h versus 24mm/h, p=0.047; respectively), and were less likely to have baseline cardiovascular comorbidities including dyslipidemia (11.8% versus 29%, p=0.037). There were no significant differences between racial groups for other disease characteristics or outcomes.
Patient race did not appear to play a significant role in determining disease characteristics and outcomes when comparing TA patients from various racial backgrounds living in the same country.
Research articleComment on "Macrophage activation syndrome in pediatric Sjögren's syndrome”
Seminars in Arthritis and Rheumatism, Volume 53, 2022, Article 151976
Research articleImpact of the number of comorbidities on the outcome measures and on the retention rate of the first anti-TNF in patients with Ankylosing Spondylitis. Two-year follow-up in REGISPONSER-AS
Seminars in Arthritis and Rheumatism, Volume 52, 2022, Article 151938
To evaluate the impact of the number of comorbidities on the outcome measures after two years of follow-up in patients with Ankylosing Spondylitis (AS) and to determine whether the number of comorbidities influences the retention rate of the first anti-TNF.
This was an observational and prospective study conducted during 2 years of follow-up in the REGISPONSER-AS registry. The patients were divided into three groups according to the number of comorbidities at baseline (0, 1 or ≥2). Linear regression models adjusted for disease duration, age, sex and smoking were constructed to evaluate the association between the number of comorbidities and the Patient Reported Outcomes (PRO) scores. The impact of the number of comorbidities on PROs over two years of follow-up was evaluated using mixed models for repeated measures adjusted for disease duration, age, sex and smoking. Finally, the retention rate of the first anti-TNF antibody across the three groups was evaluated using a log-rank test.
Patients with two or more comorbidities showed higher scores at baseline and during the two years of follow-up for the Global VAS, BASDAI, ASDAS, and BASFI and worse scores for the physical component of the SF12. A higher probability of discontinuation of the first anti-TNF was found in patients with 2 or more comorbidities compared with the patients in the other groups (38.2% vs. 26.6% vs. 25.4% for ≥2 comorbidities, 0 and 1 comorbidity, respectively), although these differences were not significant (log-rank test: p-value=0.180).
In patients with AS, the presence of 2 or more comorbidities was associated with worse scores on the outcome measures test after two years of follow-up and a greater tendency of discontinuation for the first anti-TNF.
Research articleMacrophage activation syndrome in pediatric Sjögren's syndrome
Seminars in Arthritis and Rheumatism, Volume 53, 2022, Article 151977
Research articleChange in calcinosis over 1 year using the scleroderma clinical trials consortium radiologic scoring system for calcinosis of the hands in patients with systemic sclerosis
Seminars in Arthritis and Rheumatism, Volume 53, 2022, Article 151980
Calcinosis cutis is a debilitating complication of systemic sclerosis (SSc). We previously developed a radiographic scoring system to assess severity of calcinosis affecting the hands in patients with SSc. We sought to further validate our radiographic scoring system to assess for change over 1 year and to identify factors associated with improvement or progression.
Baseline and 1-year antero-posterior hand radiographs were obtained in 39 SSc patients with calcinosis prospectively enrolled at 6 centers within the US, Canada, Mexico and Australia. Two readers (one radiologist and one rheumatologist) scored all radiographs using the calcinosis scoring system and a 5-point Likert scale (1=A lot better, 2=A little better, 3=No change, 4=A little worse, 5=A lot worse) on follow-up. By maximizing the Kappa coefficient of agreement between grouped Likert scale (better/no change/worse) and the percentage of change of calcinosis in the radiographic scoring system, we defined progressive calcinosis as >25% increase in score from baseline at 1-year, stable calcinosis as change in score between -25% to 25%, and improvement of calcinosis as decrease in score by >25%. Nineteen SSc patients from an independent cohort were used for validation.
Inter-rater reliability of the calcinosis scoring system was high with intra-class correlation coefficient of 0.93 (0.89–0.95). The median percentage of change from baseline to 1 year was 12.8% (range -89.3 to 290.2%). Sixteen patients (41%) experienced progression of calcinosis over 1 year; 18 (46%) remained stable; and 5 (13%) had improvement. Patients with progressive calcinosis had lower T-score on bone densitometry (-3.3vs -1.7, p=0.044) and higher prevalence of loss of digital pulp on physical exam (56% vs 22%, p=0.027), with a trend towards lower baseline modified Rodnan skin score (mRSS) (3.8vs. 5.9, p=0.057), than patients who did not progress. Patients who experienced improvement in calcinosis had lower prevalence of digital pitting scars (20% vs 71%, p=0.047) than patients whose calcinosis did not improve. In multivariable analysis, loss of digital pulp remained a predictor of calcinosis progression (OR 5.8, p=0.023, CI 1.27 - 26.36). In the validation cohort, 2 (11%) patients improved, 10 (53%) remained stable, and 7 (37%) progressed.
We confirmed the excellent inter-rater reliability of our radiographic calcinosis scoring system and demonstrated its usefulness to detect change over time. Approximately 40% of patients experienced progression of calcinosis over 1 year. Loss of digital pulp was predictive of progressive calcinosis providing further evidence that digital ischemia contributes to the progression of calcinosis.
Research articleProspective multicentre study of experience in real-world clinical practice in monitoring reported outcome measures (PROMs) of patient with a diagnosis of psoriatic and/or spondyloarthritis and initiating treatment with secukinumab
Reumatología Clínica (English Edition), Volume 18, Issue 1, 2022, pp. 25-29
To analyse the effect of secukinumab on self-reported variables of patients diagnosed with psoriatic arthritis and/or ankylosing spondylitis in relation to their health status, pain, fatigue, sleep and quality of life.
A six-month, observational, longitudinal, prospective, multicentre study was conducted with 39 patients who initiated treatment with secukinumab as therapy for psoriatic arthritis and/or spondylitis. The main variables were changes in patient-reported measures and they were evaluated by means of the questionnaires: FACIT-fatigue, Insomnia Severity Index, EuroQol-3L-5D and PsAQoL. In addition, depending on the type of disease (peripheral psoriasis or spondyloarthritis) the DAS28 with ESR or the BASDAI were calculated, respectively.
Levels of fatigue, moderate and severe insomnia significantly reduced after 6 months of treatment with secukinumab. At the same time, patient-reported quality of life increased significantly (P = .006). Data on pain and discomfort also show significant improvement after the treatment.
Patients with psoriatic arthritis and/or ankylosing spondylitis who start treatment with secukinumab show improvement at 6 months in all effect sizes of the treatment, particularly in sleep, fatigue and quality of life. Furthermore, patient-reported outcome measures are of additional clinical value and allow more accurate and closer assessment of their real status of health and well-being.
Analizar el efecto del secukinumab sobre las variables propias reportadas por el paciente diagnosticado de artritis psoriásica y/o espondilitis anquilosante en relación con su estado de salud, dolor, fatiga, sueño y calidad de vida.
Se realizó un estudio observacional, longitudinal, prospectivo y multicéntrico a 6 meses con 39 pacientes que iniciaron tratamiento con secukinumab para la terapia de artritis psoriásica y/o espondilitis. Las variables principales fueron los cambios en las medidas reportadas por el paciente, evaluándolas por medio de los cuestionarios FACIT-fatiga, Índice de Gravedad del Insomnio, EuroQol-3L-5D y PsAQoL. Adicionalmente, y dependiendo del tipo de enfermedad (psoriásica periférica o espondiloartritis), se recogió el DAS28 con velocidad o el BASDAI, respectivamente.
Los niveles de fatiga, insomnio moderado y grave presentan una reducción significativa tras el tratamiento de 6 meses con secukinumab. Al mismo tiempo, la calidad de vida reportada por el paciente aumenta notablemente (p = 0,006). Los datos referentes al dolor y a la incomodidad también presentan una notable mejoría tras el tratamiento.
Los pacientes de artritis psoriásica y/o espondilitis anquilosante que inician tratamiento con secukinumab presentan mejoría a los 6 meses en todos los tamaños del efecto del tratamiento, particularmente en el sueño, la fatiga y la calidad de vida. Además, las medidas de desenlace reportadas por los pacientes son un valor clínico adicional y permiten realizar una valoración más exacta y aproximada de su estado real de salud y bienestar.
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