Patients with Rheumatoid Arthritis (RA) have a higher prevalence of comorbidities, compared to the general population. The presence of such comorbidities has been directly associated with an increased disease activity. However, little is known about the impact of comorbidities in the therapeutic response and in the retention rate.
Objectives
a) To evaluate the effect of comorbidities on the first biologic disease-modifying antirheumatic drug (bDMARD) effectiveness in patients with RA after 2 years of follow-up, and b) to determine the influence of such comorbidities on the first bDMARD retention rate.
Methods
The study population consisted of patients with a diagnosis of RA and exposed to a first bDMARDs, included in BIOBADASER. BIOBADASER is a prospective, large national drug safety registry of patients with rheumatic diseases exposed to b- or tsDMARDs. Patients were classified in two groups at baseline according to the Charlson Comorbidity index (CCI) score: <3 and ≥3. Patients achieving remission (DAS28<2.6) at 1 and 2-years timepoints after the anti-TNF initiation were compared between the two groups using chi-square test. The absolute DAS28 score over time was compared between both groups of patients using a linear regression model adjusted for sex and age, and considering the follow-up visit as covariate. Finally, the first bDMARD retention rate was compared between patients <3 and ≥3 using Log-Rank test and Kaplan-Meier curve.
Results
A total of 1253 patients initiating bDMARD were included (76.6% female and mean age 56 years at the beginning of therapy). Overall, 107 (9%) patients had a CCI ≥3, being diabetes the most frequent comorbidity (5.0%). No differences were found in DAS28<2.6 between patients with CCI<3 and CCI≥3 after 1 year of follow-up (48.2% vs. 44.2%, p-value=0.457), nor after 2 years (50.8% vs. 40.7%, p-value=0.135). The linear regression model showed significant higher scores in DAS28 over the two years in patients with a CCI ≥3 after adjusting for age and sex (beta coefficient 0.27, 95%CI: 0.02-0.51; p-value=0.034). Finally, no differences in the bDMARD retention rate were found between both groups (median 2.6 years [IQR: 1.5-4.1] in CCI<3 vs. 2.1 years [IQR: 0.6-3.7] in CCI≥3; log rank test p-value 0.467) (Figure 1).
Conclusion
These data suggest that a higher CCI in patients with RA is associated with greater DAS28 scores during the first two years after bDMARD initiation, although no differences in remission status were found. In addition, a slightly shorter retention rate was found in patients with CCI≥3, although the difference was non-significant. These results suggest a lower probability of disease activity control in patients with comorbidities after the initiation of bDMARD.
Abstract Aim To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors. Methods Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab >6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). Results Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0–73.9) at year 1% and 37.7% (95% CI: 33.3–42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p < 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first‐line therapy (hazard ratio [HR] for discontinuation 1.52 for second‐ and 1.79 for third/later‐line vs. first‐line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation. Conclusion Based on this retrospective analysis of the BIOBADASER registry, nearly two‐fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.
Psoriasis and psoriatic arthritis (PsA) are described as associated with more frequency of risk factors and cardiovascular events.
Objectives
To determine the prevalence of risk factors and cardiovascular events in a cohort of patients with PsA treated with biological therapy and its correlation with gender.
Methods
We included all PsA patients (met CASPAR criteria) following treatment with bDMARDs (reference population 2.055.000). We obtained data of high blood pressure, hyperlipidemia, hyperuricemia, type 2 diabetes mellitus, obesity (BMI ≥30), non-infectious liver disease, ischaemic cardiopathy, myocardial infarction, ischaemic stroke or transient ischaemic attack. For this analysis included gender, age, disease duration, current bDMARDs with or without current co-medication with csDMARDs and HLA-B27 status. Continuous variables were reported as mean ±standard deviation. Categorical variables were reported as percentages and frequencies. All analyses were performed using SPSS software. Differences were considered statistically significant if p<0.05 (two-tailed).
Results
Data were obtained from 598 PsA patients who have been treated with bDMARDs. Three-hundred and twenty-five (54.3%) patients were men, mean age was 53.3±12.6 years (men 53.3±12.9 and women 53.2±12.3, p=0.943) and disease duration of PsA was 12.4±8.7 years. No differences were seen for disease duration of PsA, nail disease, dactylitis, uveitis or HLA-B27. The prevalence of high blood pressure, hyperlipidemia, hyperuricemia, type 2 diabetes mellitus, obesity, non-infectious liver disease, ischaemic cardiopathy, myocardial infarction (MI) and ischaemic stroke/transient ischaemic attack (IS) was 36.0%, 43.6%, 16.0%, 12.5%, 26.3%, 12.5%, 5.5%, 3.8% and 1.3%, respectively. Men had most prevalence of type 2 diabetes mellitus, hyperuricemia, non-infectious liver disease, ischaemic cardiopathy, myocardial infarction and brain stroke event (see table 1). Patients with MI or IS had more prevalence of CV risk factors.
Conclusions
Type 2 diabetes mellitus, hyperuricemia, non-infectious liver disease, ischaemic cardiopathy, myocardial infarction and brain stroke event were more prevalent in men than in women with PsA. Male gender had correlation with the prevalence of cardiovascular events or their risk factors.
Reference
[1] Husted JA, et al. Cardiovascular and other comorbidities in patients with psoriatic arthritis: A comparison with patients with psoriasis. Arthritis Care Res (Hoboken)2011Dec;63(12):1729–35.
Acknowledgements
The authors are grateful for the support of the members of the Galician Society of Rheumatology (SOGARE)
To evaluate adherence to treatment in a cohort of patients with rheumatoid arthritis in Spain and to identify potential predictors of adherence.An observational, cross-sectional, multicenter study in outpatient clinics of Rheumatology Departments from 41 centers was conducted. A validated Spanish version of the compliance questionnaire in Rheumatology was used to measure adherence in a cohort of patients with rheumatoid arthritis, representative of the Spanish population. Univariate and multivariate analyses were performed to detect predictors of adherence.A total of 859 patients were recruited. An adherence rate of 79% was established. No differences were detected in adherence in patients receiving biologic disease-modifying antirheumatic drugs compared to conventional disease-modifying antirheumatic drugs, in patients receiving intravenous therapies compared to other routes of administration and in patients treated in specific day hospitals compared to polyvalent day hospitals. The number of drugs and cohabitation were independent predictors of adherence.An inexpensive and useful method was used to measure adherence in Spanish population. The adherence rate in rheumatoid arthritis is still suboptimal. Simpler, more convenient dosing regimens may improve compliance. Increased knowledge of compliance in patients with rheumatoid arthritis and the identification of possible predictors of adherence will allow to develop effective intervention strategies.
To assess the impact of 'patient's minus evaluator's global assessment of disease activity' (ΔPEG) at treatment initiation on retention and remission rates of TNF inhibitors (TNFi) in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients across Europe.Real-life data from PsA and axSpA patients starting their first TNFi from 11 countries in the European Spondyloarthritis Research Collaboration Network were pooled. Retention rates were compared by Kaplan-Meier analyses with log-rank test and by Cox regression, and remission rates by χ2 test and by logistic regression across quartiles of baseline ΔPEG, separately in female and male PsA and axSpA patients.We included 14 868 spondyloarthritis (5855 PsA, 9013 axSpA) patients. Baseline ΔPEG was negatively associated with 6/12/24-months' TNFi retention rates in female and male PsA and axSpA patients (P <0.001), with 6/12/24-months' BASDAI < 2 (P ≤0.002) and ASDAS < 1.3 (P ≤0.005) in axSpA patients, and with DAS28CRP(4)<2.6 (P ≤0.04) and DAPSA28 ≤ 4 (P ≤0.01), but not DAS28CRP(3)<2.6 (P ≥0.13) in PsA patients, with few exceptions on remission rates. Retention and remission rates were overall lower in female than male patients.High baseline patient's compared with evaluator's global assessment was associated with lower 6/12/24-months' remission as well as retention rates of first TNFi in both PsA and axSpA patients. These results highlight the importance of discordance between patient's and evaluator's perspective on disease outcomes.
There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries.Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses.A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (<2/2-4/>4 years), and varied significantly across the European registries.In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.
Background: Previous studies have suggested similar effectiveness, but longer treatment retention, for tumor necrosis factor inhibitors (TNFi), when used in combination with a conventional synthetic disease modifying anti-rheumatic drug (csDMARD) in psoriatic arthritis (PsA). Objectives: To describe patients with PsA initiating a first TNFi as monotherapy compared to combination therapy, and to explore 1-year treatment retention of TNFi in the two groups. Methods: Patients with PsA starting a first TNFi (2006-2017) were identified in biologics registers of 13 European countries, and data were pooled for analysis. Co-medication with csDMARD was determined at TNFi start. Because of large inter-country variation in TNFi retention, countries were split into two strata, depending on each country’s 1-year retention rate for TNFi being above (stratum A) or below (stratum B) the average 1-year retention rate. TNFi treatment retention was compared through Kaplan-Meier curves; the proportion remaining on the TNFi at one year; and hazard ratios (HR) during the first year: (i) crude; adjusted for (ii) country-strata, and (iii) country-strata, sex, age, calendar year, DAS28 and disease duration. In model (iii) only registers contributing >1000 patients or <33% missing data for DAS28 were included. Results: A total of 14778 patients with PsA starting a first TNFi were included. Baseline disease activity was similar within stratum B, but higher for the combination treatment group in stratum A (table 1). Table 1. Baseline characteristics Country strata Stratum A Stratum B TNFi monotherapy N=2120 TNFi/csDMARD combination N=2128 TNFi monotherapy N=3369 TNFi/csDMARD combination N=7161 Females 52% 51% 53% 51% Age, years 49.7 (12.2) 48.7 (11.8) 48.8 (13.0) 48.9 (12.2) Disease duration, yrs 6.4 (7.0) 6.8 (6.8) 5.9 (7.5) 5.9 (7.1) Tender joints 28 5.5 (6.3) 8.0 (6.3) 5.6 (6.0) 5.6 (5.7) Swollen joints 28 2.8 (4.3) 5.6 (5.0) 3.0 (3.8) 3.3 (3.8) VAS pain 54 (29) 62 (24) 59 (23) 56 (24) DAPSA-28 24.6 (18.6) 36.2 (17.6) 27.3 (15.6) 27.2 (15.2) DAS28 (CRP) 3.5 (1.4) 4.7 (1.3) 4.0 (1.2) 4.0 (1.1) Concomitant csDMARD Methotrexate - 76% - 79% Sulfasalazine - 15% - 15% Other csDMARD - 49% - 25% Numbers are means (sd) unless otherwise stated. The Kaplan-Meier curves for the treatment groups were similar within each stratum (fig 1), as were the proportions remaining on TNFi after one year, stratum A: monotherapy 86% (95%CI: 85-88) vs. combination 86% (84-87), stratum B: 71% (69-72) vs. 73% (72-74). The HRs for TNFi discontinuation (ref=TNFi monotherapy) were: (i) 1.06 (0.98-1.13), (ii) 0.94 (0.87-1.01), (iii) 0.89 (0.83-0.96), including 13078 patients (9 countries) for model (iii). Conclusion: In this exploratory study no benefit in TNFi retention was observed for csDMARD combination therapy in crude analyses, while in adjusted analyses an 11% lower risk of TNFi discontinuation was found. These preliminary results offer limited support for use of combination therapy in PsA. Further analyses will explore to what extent the results are affected by inter-country heterogeneity and differences between TNFi. Acknowledgments: UL and DDG contributed equally. Novartis Pharma AG and IQVIA support the EuroSpA collaboration. Disclosure of Interests: Ulf Lindström: None declared, Daniela Di Giuseppe: None declared, Bénédicte Delcoigne: None declared, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Burkhard Moeller: None declared, Manuel Pombo-Suarez Consultant of: Janssen, Lilly, MSD and Sanofi., Speakers bureau: Janssen, Lilly, MSD and Sanofi., Carlos Sánchez-Piedra: None declared, Kari Eklund Consultant of: Celgene, Lilly, Speakers bureau: Pfizer, Roche, Heikki Relas Grant/research support from: Abbvie., Consultant of: Abbvie, Celgene, and Pfizer., Speakers bureau: Abbvie, Celgene, and Pfizer., Björn Gudbjornsson Speakers bureau: Novartis and Amgen, Thorvardur Love: None declared, Gareth T. Jones Grant/research support from: Pfizer, AbbVie, UCB, Celgene and GSK., Adrian Ciurea Consultant of: Consulting and/or speaking fees from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Novartis and Pfizer., Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Ruxandra Ionescu Consultant of: Consulting fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Speakers bureau: Consulting and speaker fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Lucie Nekvindova: None declared, Jakub Zavada Speakers bureau: Abbvie, UCB, Sanofi, Elli-Lilly, Novartis, Zentiva, Accord, Nuh Atas: None declared, Servet Yolbaş: None declared, Karen Fagerli: None declared, Brigitte Michelsen Grant/research support from: Research support from Novartis, Consultant of: Consulting fees Novartis, Ziga Rotar Consultant of: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Speakers bureau: Speaker and consulting fees from Abbvie, Amgen, Biogen, Eli Lilly, Medis, MSD, Novartis, Pfizer, Roche, Sanofi., Matija Tomsic: None declared, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Pedro Ávila-Ribeiro Grant/research support from: Novartis, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Mikkel Ǿstergaard Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Merck, and Novartis, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Michael Nissen Grant/research support from: Abbvie, Consultant of: Novartis, Lilly, Abbvie, Celgene and Pfizer, Speakers bureau: Novartis, Lilly, Abbvie, Celgene and Pfizer
Luis Cea-Calvo, is employed by MSD España, Madrid, Spain. The rest of the authors declared no conflicts of interest. The data base used for this study is not publicly available. If you need additional information, please address the corresponding author.
