scholarly journals AB0233 REASONS AND RISK FACTOR FOR DISCONTINUATION OF BIOLOGIC AGENTS FOR RHEUMATOID ARTHRITIS PATIENTS IN LONG-TERM OBSERVATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1142.3-1143
Author(s):  
K. Terabe ◽  
N. Takahashi ◽  
S. Asai ◽  
Y. Hirano ◽  
Y. Kanayama ◽  
...  

Background:Rheumatoid arthritis (RA) patients who failed a first biologic agent due to any reasons have the option of switching to a second one along with the strategy of biologic agent treatment. Patients go over switching to the next one at failing their biologic agent. On the other hand, there are some patients who discontinue any biologic agent treatment due to various reasons such as tolerability concern, complications, economic issue, remission and so on1 2. The impact of this concern has been less studied.Objectives:The objective of this study was to investigate the reasons and the risk factors for discontinuation any biologic agent in RA patients.Methods:To Include patients who are observed long-term, patients who underwent biologic agent treatment between 2003 and 2007 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group) were enrolled. 570 patients who were confirmed continuation or discontinuation of biologic agent treatment were enrolled. The last observation was September 2017. We analyzed the retention rate of biologic agent treatment and the reasons for discontinuation. To identify the risks for discontinuation, baseline demographics were compared between the continuing group and the disc continuing group using cox hazard regression analysis.Results:In total 570 patients, the average duration of treatment with biologics was 6.6±3.3 (years) and total patient-year was 3739 in this study. 458 patients were administered biologics continuously, 112 patients were withdrawn. Table 1 showed the demographic data in total patients. The retention rate was 96.0% (discontinuation n=23) at least 1 year from starting biologics treatment, 92.6% (n=42) at 3 years, 88.2% (n=67) at 5 years, 84.4% (n=89) at 7 years, 81.1% (n=108) at 10 years. In 112 patients who discontinued, the reasons were adverse events in 74 patients, lack of effectiveness in 11 patients, others in 27 patients. Comparison of incidence for discontinuation using cumulative hazard function, the reason of adverse events was significantly higher than others reasons (Figure 1). To identify the risks of discontinuation, we analyzed by multivariable Cox proportional hazard modeling in patients who discontinued treatment due to adverse events, the risk factors (hazard ratio: HR, confidence interval: CI) were over 3 of Steinblocker class (HR 1.85 [1.02-2.04]), age (HR:1.07 [1.04-1.10]) and Non-concomitant with methotrexate (HR 1.90 [1.08-3.33]) (Figure 2).Table 1.Age (years)56.1 ± 13.4Gender n (% male)110 (19%) n (% female)460 (81%)Disease duration (years)11.1 ± 9.8stage 1,2104 (19%) 3,4455 (81%)class 1,2336 (60%) 3,4225 (40%)Methotrexate use, no (%)400 (70%)Glucocorticoid use, no (%)262 (47%)Rheumatoid Factor, no (%)287 (65%)anti CCP antibody, no (%)137 (87%)Conclusion:The most common reason for discontinuation was adverse events in long term observation. The risk factors for discontinuation were class, age, and non-concomitant MTX. These results suggested that comorbidity has a significant impact on continuation rates because there are some reasons of non-concomitant MTX in addition to relate with age and the activities of daily living.References:[1]Marussa B, et al. j.clin thera. 2011; 33(7): 901-913[2]Alejandro S, et al. Rheumatol. 2016; 55(3): 523-34Disclosure of Interests:KENYA TERABE: None declared, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Yasuhide Kanayama: None declared, Toshihisa Kojima Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Consultant of: AbbVie, Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 559.2-560
Author(s):  
V. Rivera Teran ◽  
S. Sicsik ◽  
D. Vega-Morales ◽  
F. Irazoque-Palazuelos ◽  
D. Miranda ◽  
...  

Background:Rheumatoid arthritis (RA) is the most common autoimmune disease. Older patients treated with biologic DMARDs (bDMARDs) are at a significantly greater risk of adverse effects (AEs) [1]. However, the rate of drug discontinuation because of adverse effects caused by bDMARDs has not differed in elderly compared to younger patients in different registries.Objectives:Determine if drug discontinuation of bDMARDs differs by age in patients with rheumatoid arthritis in the Mexican Adverse Events Registry (BIOBADAMEX).Methods:BIOBADAMEX is a Mexican ongoing cohort of patients using bDMARDs since 2016. In this analysis we included all patients with diagnosis of RA with at least two assessments. Survival on bDMARDs was estimated using Kaplan-Meier analysis. Predictors of discontinuation, including age older than median age in the sample were investigated by Cox regression analyses.Results:Among 743 patients in the registry, 497 had RA diagnosis, from which, 214 had at least two assessments. At baseline, patients had a median (IQR) age of 53.4 (45-61) years old, median disease duration of 10.7 (6-17) months and median DAS28 of 4.7 (3-6). Conventional DMARDS were used by 185 (87%) patients and 94 (44%) patients used corticosteroids. Comorbidities were present in 194 (91%). The most common bDMARDs received at baseline were abatacept 59 (27%), tocilizumab 45(21%), adalimumab 31 (15%) and certolizumab 30 (14%). At the time of analysis, the median bDMARDs treatment duration was 21.0(13-34) months, 128 (59%) had discontinued treatment, 66 for inefficacy, 32 for adverse events and 30 for others. Fig 1 shows discontinuation rate curves in patients younger and older than median age. Cox proportional-hazards demonstrated no significant differences regarding age older than median age (HR 1.1, 95% CI 0.8-1.4, p=0.7), female sex (HR 1.2, 95% CI 0.7-1.9, p=0.44), use of corticosteroids (HR 1.2, 95% CI 0.9-1.6, p=0.20), comorbidities (HR 0.9, 95% 0.6-1.5, p=0.78), DAS28 (HR 0.9, 95% 0.9-1.1, p=0.93) or other factors.Figure 1.Discontinuation rate curves in patients younger and older than median age (< 53.4 and >=53.4 years old)Conclusion:This analysis did not show a role of age on discontinuation of bDMARDs in Mexican RA patients. Further longitudinal analyses will be performed including more patients to assess retention rate of bDMARDs and identify predictive variables of discontinuation in Mexican population.References:[1]Akter R, et al. Can Geriatr J. 2020 May 1;23(2):184-189.[2]Ikari Y, et al. Medicine (Baltimore). 2020 Dec 24;99(52):e23861.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 545-546
Author(s):  
D. Bertrand ◽  
N. Pype ◽  
T. Conings ◽  
D. De Cock ◽  
S. Pazmino ◽  
...  

Background:Rituximab is known as an efficacious drug for the treatment of Rheumatoid Arthritis (RA). The recommended administration schedule consist of 2 infusions of 1000 mg with a 2-week interval. In Belgium an on-flare retreatment strategy is followed, making evaluation of effectiveness over time challenging. Moreover the patient’s view on this strategy is unclear.Objectives:To explore long-term effectiveness and safety of rituximab in daily clinical practice in patients with RA.Methods:Data of patients diagnosed with RA and treated with rituximab in a tertiary university hospital were retrospectively collected. For every cycle, clinical data were recorded at the time of the first and second infusion, the 16-week visit and the visit on which the treating rheumatologist decided to prescribe a new cycle. Data on demographics, previous RA treatment, disease activity, patient-reported outcomes, adverse events related to rituximab, dose and number of cycles were collected from 01/01/2006 until 01/12/2019 or until discontinuation of rituximab. The visit on which rituximab was prescribed for the first time was considered as the baseline visit. The data were analysed descriptively.Results:Data of 66 patients with RA were collected. The median (IQR) age was 57.0 (47.0-65.0) years at baseline and 56% (37/66) were female. Most patients were seropositive (RF 91% and ACPA 92%), and had erosive (71%) or nodular disease (53%). The median (IQR) disease duration was 12.5 (4.0-18.3) years. In total, 94% of the patients had failed at least one other biological Disease-modifying Antirheumatic Drug (bDMARD) before starting rituximab. Overall, patients received a median (IQR) of 3 (2-7) cycles of rituximab. Seven of the 66 patients (11%) discontinued rituximab and changed to another bDMARD after a median (IQR) of 1 (1-6) cycles and 11% were treated with a lower dose than 2x1000mg. The median (IQR) interval between the first 2 cycles was 7.0 (6.0-10.0) months, after which this increased to up to one year (interval between cycle 2-3: 10.0 (7.0-13.0) months, cycle 3-4: 12.0 (7.3-15.5) months). The overall median (IQR) follow-up time was 45.5 (14.8-82.3) months. The efficacy of rituximab remained after repeated cycles: after every treatment with rituximab, a reduction in disease activity based on the disease activity score in 28 joints (DAS28) could be noticed (figure 1A). The evolution in patients’ (PaGH) and physicians’ global health (PhGH) assessment followed the same pattern as the DAS28-score (Figure 1B). High PaGH-scores could be noticed at every start of a new rituximab cycle. The proportion of patients with a PaGH-score above 20 ranged from 84% - 100%, 74% - 100% and 66% - 86% at the first infusion, second infusion and week 16 visits, respectively. Rituximab was considered to be well-tolerated. In total, 23 adverse events in 12 patients were recorded and none of them were serious.Conclusion:Rituximab can be considered a highly efficacious drug for RA treatment in daily practice. There were no major side effects and there was an increasing treatment interval over time. However, a healthy survivor effect should be kept in mind when interpreting the results. It should be noted that with the on-flare retreatment strategy, every new rituximab cycle was preceded by a rise in PaGH-scores, which reflects a state of impaired wellbeing reported by patients. This should be further studied with qualitative methods and in a randomized trial setting comparing on-flare with fixed-interval retreatment to evaluate optimal effectiveness.Figure 1.Evolution in median - interquartile range disease activity (DAS28CRP) (A) and patients’ (PaGH) and physicians’ global health (PhGH) (B) over the different rituximab cycles. The disease activity, PaGH and PhGH were measured at baseline, the time of the first and second infusion, W16 and the visit on which a new rituximab cycle was prescribed. The dotted lines represent a DAS28CRP-score of 2.6 (remission cut-off) and 3.2 (low disease activity cut-off). C: cycle; W: week; VAS: visual analogue scale.Disclosure of Interests:None declared


2017 ◽  
Vol 76 (9) ◽  
pp. 1583-1590 ◽  
Author(s):  
Y Meissner ◽  
A Richter ◽  
B Manger ◽  
HP Tony ◽  
E Wilden ◽  
...  

ObjectiveIn the general population, the incidence of stroke is increased following other serious events and hospitalisation. We investigated the impact of serious adverse events on the risk of stroke in patients with rheumatoid arthritis (RA), taking risk factors and treatment into account.MethodsUsing data of the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) with 12354 patients with RA, incidence rates (IRs) and risk factors for stroke were investigated using multi-state and Cox proportional hazard models. In addition, in a nested case–control study, all patients with stroke were matched 1:2 to patients with identical baseline risk profile and analysed using a shared frailty model.ResultsDuring follow-up, 166 strokes were reported. The overall IR was 3.2/1000 patient-years (PY) (95% CI 2.7 to 3.7). It was higher after a serious adverse event (IR: 9.0 (7.3 to 11.0)), particularly within 30 days after the event (IR: 94.9 (72.6 to 121.9)). The adjusted Cox model showed increased risks of age per 5 years (HR: 1.4 (1.3 to 1.5)), hyperlipoproteinaemia (HR: 1.6 (1.0 to 2.5)) and smoking (HR: 1.9 (1.3 to 2.6)). The risk decreased with better physical function (HR: 0.9 (0.8 to 0.96)). In the case–control study, 163 patients were matched to 326 controls. Major risk factors for stroke were untreated cardiovascular disease (HR: 3.3 (1.5 to 7.2)) and serious infections (HR:4.4 (1.6 to 12.5)) or other serious adverse events (HR: 2.6 (1.4 to 4.8)).ConclusionsIncident adverse events, in particular serious infections, and insufficient treatment of cardiovascular diseases are independent drivers of the risk of stroke. Physicians should be aware that patients who experience a serious event are at increased risk of subsequent stroke.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
E. G. Favalli ◽  
F. Iannone ◽  
E. Gremese ◽  
R. Gorla ◽  
R. Foti ◽  
...  

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


Author(s):  
Simo S. A. Miettinen ◽  
Hannu J. A. Miettinen ◽  
Jussi Jalkanen ◽  
Antti Joukainen ◽  
Heikki Kröger

Abstract Introduction This retrospective study investigated the long-term follow-up results of medial opening wedge high tibial osteotomy (MOWHTO) with a pre-countered non-locking steel plate implant (Puddu plate = PP) used for medial knee osteoarthrosis (OA) treatment. Materials and methods Consecutive 70 MOWHTOs (66 patients) were performed between 01.01.2004 and 31.12.2008 with the mean follow-up time of 11.4 (SD 4.5; range 1.2–16.1) years. The Kaplan–Meier survival analysis was used to evaluate the cumulative survival of the implant in terms of age (< 50 years old and ≥ 50 years old) and gender. Adverse events were studied and Cox regression analysis was used to evaluate risk factors [age, gender, body mass index (BMI), preoperative mechanical axis, severity of OA, use of bone grafting or substitution and undercorrection of mechanical axis from varus to valgus] for revisions. Results The estimates for the cumulative survival with no need for TKA after MOWHTO were 86% at 5 years, 67% at 10 years and 58% at 16.1 years (SE 0.6, CI 95% 11.1–13.5). A total of 33/70 (47%) adverse events occurred and 38/70 (54%) knees required some revision surgery during the follow-up. Cox regression did not show any statistically significant risk factors for revision. Conclusions The PP has feasible MOWHTO results with a cumulative survival of 67% at 10 years with no need for conversion to TKA. Many adverse events occurred and revision rate due to any reason was high. Age or gender did not have statistically significant differences in terms of survival.


2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Gorica G. Ristić ◽  
Vesna Subota ◽  
Dejana Stanisavljević ◽  
Danilo Vojvodić ◽  
Arsen D. Ristić ◽  
...  

Abstract Objective To explore glucose metabolism in rheumatoid arthritis (RA) and its association with insulin resistance (IR) risk factors and disease activity indicators, including matrix metalloproteinase-3 (MMP3). Methods This single-center study included 127 non-diabetic subjects: 90 RA patients and 37 matched controls. IR-related risk factors, disease activity (DAS28-ESR/CRP), concentrations of inflammation markers, MMP3, glucose, specific insulin, and C-peptide (a marker of β-cell secretion) were determined. Homeostasis Model Assessment was used to establish insulin resistance (HOMA2-IR) and sensitivity (HOMA2-%S). Associations of HOMA2 indices with IR-related risk factors, inflammation markers, and RA activity were tested using multiple regression analyses. Results RA patients had significantly increased HOMA2-IR index than controls. In the RA group, multivariate analysis revealed DAS28-ESR, DAS28-CRP, tender joint counts, patient’s global assessment, and MMP3 level as significant positive predictors for HOMA2-IR (β = 0.206, P = 0.014; β = 0.192, P = 0.009; β = 0.121, P = 0.005; β = 0.148, P = 0.007; β = 0.075, P = 0.025, respectively), and reciprocal negative for HOMA2-%S index. According to the value of the coefficient of determination (R2), DAS28-ESR ≥ 5.1 has the largest proportion of variation in both HOMA2-IR indices. DAS28-ESR ≥ 5.1 and ESR were independent predictors for increased C-peptide concentration (β = 0.090, P = 0.022; β = 0.133, P = 0.022). Despite comparability regarding all IR-related risk factors, patients with DAS28-ESR ≥ 5.1 had higher HOMA2-IR than controls [1.7 (1.2–2.5) vs. 1.2 (0.8–1.4), P = 0.000]. There was no difference between patients with DAS28-ESR < 5.1 and controls [1.3 (0.9–1.9) vs. 1.2 (0.8–1.4), P = 0.375]. Conclusions RA activity is an independent risk factor for impaired glucose metabolism. DAS28-ESR ≥ 5.1 was the main contributor to this metabolic disturbance, followed by MMP3 concentration, outweighing the impact of classic IR-related risk factors.


2017 ◽  
Vol 77 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Cynthia S Crowson ◽  
Silvia Rollefstad ◽  
Eirik Ikdahl ◽  
George D Kitas ◽  
Piet L C M van Riel ◽  
...  

ObjectivesPatients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA.MethodsIn 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions.Results5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics).ConclusionsIn a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sheng-Fu Liu ◽  
Chih-Kuo Lee ◽  
Kuan-Chih Huang ◽  
Lian-Yu Lin ◽  
Mu-Yang Hsieh ◽  
...  

Objectives: Rheumatoid arthritis (RA) is an independent nontraditional risk factor for incidence of myocardial infarction (MI) and post-MI outcome is impaired in the RA population. Use of beta-blockers improves the long-term survival after MI in the general population while the protective effect of beta-blockers in RA patients is not clear. We investigate the impact of beta-blockers on the long-term outcome of MI among RA patients.Methods: We identified RA subjects from the registries for catastrophic illness and myocardial infarction from 2003 to 2013. The enrolled subjects were divided into three groups according to the prescription of beta-blockers (non-user, non-selective, and β1-selective beta-blockers). The primary endpoint was all-cause mortality. We adjusted clinical variables and utilized propensity scores to balance confounding bias. Cox proportional hazards regression models were used to estimate the incidence of mortality in different groups.Results: A total of 1,292 RA patients with myocardial infarction were enrolled, where 424 (32.8%), 281 (21.7%), and 587 (45.5%) subjects used non-user, non-selective, and β1-selective beta-blockers, respectively. Use of beta-blockers was associated with lower risk of all-cause mortality after adjustment with comorbidities, medications (adjusted hazard ratio [HR] 0.871; 95% confidence interval [CI] 0.727–0.978), and propensity score (HR 0.882; 95% CI 0.724–0.982). Compared with β1-selective beta-blockers, treatment with non-selective beta-blockers (HR 0.856; 95% CI 0.702–0.984) was significantly related to lower risk of mortality. The protective effect of non-selective beta-blockers remained in different subgroups including sex and different anti-inflammatory drugs.Conclusion: Use of beta-blockers improved prognosis in post-MI patients with RA. Treatment with non-selective beta-blockers was significantly associated with reduced risk of mortality in RA patients after MI rather than β1-selective beta-blockers.


Sign in / Sign up

Export Citation Format

Share Document