scholarly journals POS0642 THE IMPACT OF AGE ON DISCONTINUATION OF BIOLOGIC DMARDs IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 559.2-560
Author(s):  
V. Rivera Teran ◽  
S. Sicsik ◽  
D. Vega-Morales ◽  
F. Irazoque-Palazuelos ◽  
D. Miranda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Effects ◽  
Adverse Events ◽  
Cox Regression ◽  
Retention Rate ◽  
Drug Discontinuation ◽  
Discontinuation Rate ◽  
Biologic Dmards ◽  
Conventional Dmards ◽  
The Impact

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

Longterm Retention Rate and Risk Factor for Discontinuation Due to Insufficient Efficacy and Adverse Events in Japanese Patients with Rheumatoid Arthritis Receiving Etanercept Therapy

2014 ◽  
Vol 41 (8) ◽  
pp. 1583-1589 ◽  
Author(s):  
Hiroyuki Matsubara ◽  
Toshihisa Kojima ◽  
Atsushi Kaneko ◽  
Yuji Hirano ◽  
Hisato Ishikawa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factor ◽  
Adverse Events ◽  
Retention Rate ◽  
Drug Evaluation ◽  
Japanese Patients ◽  
Retention Rates ◽  
Rank Test ◽  
Drug Discontinuation ◽  
Discontinuation Rate

Objective.Assessing retention rate and risk factor for drug discontinuation is important for drug evaluation. We examined a 3-year retention rate and the risk factor for discontinuation due to insufficient efficacy (IE) and adverse events (AE) in Japanese patients with rheumatoid arthritis (RA) who are receiving etanercept (ETN).Methods.Data were collected from 588 patients treated with ETN as a first biologic from the Tsurumai Biologics Communication Registry. Baseline characteristics for the incidence of both IE and AE were analyzed using the Cox proportional-hazards regression model. Patients were divided into groups based on age and concomitant methotrexate (MTX). Drug retention rates were calculated using the Kaplan-Meier method and compared among groups using the log-rank test.Results.ETN monotherapy without concomitant MTX [MTX(–)] was significantly related to a higher incidence of discontinuation due to IE [hazard ratio (HR) = 2.226, 95% CI 1.363–3.634]. Older age and MTX(–) were significantly related to a higher incidence of discontinuation due to AE [HR = 1.040, 1.746, 95% CI 1.020–1.060, 1.103–2.763, respectively]. The MTX(–)/≥ 65 years group had the lowest retention rate (p < 0.001). The discontinuation rate due to IE was lower in the MTX(+)/< 65 years group compared to < 65 years/MTX(–), ≥ 65 years/MTX(–) group (p = 0.006, p < 0.001, respectively). The discontinuation rate due to AE was highest in the MTX(–)/≥ 65 years group (p < 0.001).Conclusion.Our findings suggest that the risk of discontinuation due to IE was high in the patients who did not use concomitant MTX and that the risk of discontinuation due to AE was high in elderly patients who did not use concomitant MTX.

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 ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Adverse Events ◽  
Retention Rate ◽  
University Hospital ◽  
Biologic Agent ◽  
Long Term Observation ◽  
The Impact ◽  
Agent Treatment

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

The impact of seropositivity on the effectiveness of biologic anti-rheumatic agents: results from a collaboration of 16 registries

Rheumatology ◽  
2020 ◽  
Author(s):  
Delphine S Courvoisier ◽  
Katarina Chatzidionysiou ◽  
Denis Mongin ◽  
Kim Lauper ◽  
Xavier Mariette ◽  
...  
Keyword(s):  
Disease Activity ◽  
Cox Regression ◽  
Activity Index ◽  
Disease Activity Index ◽  
Pooled Analysis ◽  
Diagnostic Tools ◽  
Drug Discontinuation ◽  
Biologic Dmards ◽  
Low Disease Activity ◽  
The Impact

Abstract Objectives RF and ACPA are used as diagnostic tools and their presence has been associated with clinical response to some biologic DMARDs (bDMARDs) in RA. This study compared the impact of seropositivity on drug discontinuation and effectiveness of bDMARDs in patients with RA, using head-to-head comparisons in a real-world setting. Methods We conducted a pooled analysis of 16 observational RA registries. Inclusion criteria were a diagnosis of RA, initiation of treatment with rituximab (RTX), abatacept (ABA), tocilizumab (TCZ) or TNF inhibitors (TNFis) and available information on RF and/or ACPA status. Drug discontinuation was analysed using Cox regression, including drug, seropositivity, their interaction, adjusting for concomitant and past treatments and patient and disease characteristics and accounting for country and calendar year of bDMARD initiation. Effectiveness was analysed using the Clinical Disease Activity Index evolution over time. Results Among the 27 583 eligible patients, the association of seropositivity with drug discontinuation differed across bDMARDs (P for interaction &lt;0.001). The adjusted hazard ratios for seropositive compared with seronegative patients were 1.01 (95% CI 0.95, 1.07) for TNFis, 0.89 (0.78, 1.02)] for TCZ, 0.80 (0.72, 0.88) for ABA and 0.70 (0.59, 0.84) for RTX. Adjusted differences in remission and low disease activity rates between seropositive and seronegative patients followed the same pattern, with no difference in TNFis, a small difference in TCZ, a larger difference in ABA and the largest difference in RTX (Lundex remission difference +5.9%, low disease activity difference +11.6%). Conclusion Seropositivity was associated with increased effectiveness of non-TNFi bDMARDs, especially RTX and ABA, but not TNFis.

scholarly journals POS0675 THE COMPARATIVE 3-YEAR RETENTION RATE OF TARGETED-SYNTHETIC AND BIOLOGIC DRUGS FOR RHEUMATOID ARTHRITIS: REAL-LIFE DATA FROM THE ITALIAN GISEA REGISTRY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 582.1-582
Author(s):  
E. G. Favalli ◽  
F. Iannone ◽  
E. Gremese ◽  
R. Gorla ◽  
R. Foti ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Retention Rate ◽  
Large Population ◽  
Real Life ◽  
Mechanisms Of Action ◽  
Biologic Drugs ◽  
Real Life Setting ◽  
Study Population ◽  
Targeted Drug

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

scholarly journals POS0460 ASSOCIATION OF ANTI-CITRULLINATED PROTEIN ANTIBODIES OF IgA SUBCLASSES WITH SUSTAINED REMISSION AND FLARE IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 461-461
Author(s):  
M. V. Sokolova ◽  
J. Rech ◽  
M. Hagen ◽  
G. Schett ◽  
U. Steffen (née Harre)
Keyword(s):  
Rheumatoid Arthritis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sustained Remission ◽  
Das28 Score ◽  
Effector Functions ◽  
Conventional Dmards ◽  
The Impact ◽  
Citrullinated Protein ◽  
Iga Subclasses ◽  
Over Time

Background:Understanding key mechanisms of flare development and sustained remission is one of the acute goals in modern rheumatology. Anti-citrullinated protein antibodies (ACPA) are the most abundant and specific autoantibodies in rheumatoid arthritis (RA) patients. However, the impact of ACPA of IgA isotype is poorly defined. IgA ACPA were previously shown to have a higher percentage of IgA2 in comparison to total IgA; and a correlation between IgA2% ACPA with the DAS28 score was observed in a previous study [1]. Of note, IgA1 and IgA2 were shown to exhibit different effector functions, with IgA2 being pro-inflammatory, which might be the background for its role in RA [1].Objectives:We aimed to investigate, whether IgA ACPA could be used as a predictive factor for flare development in RA; and to look further into the changes in IgA ACPA levels in patients remaining in stable remission versus patients developing flare.Methods:We analysed serum of 111 patients from a multicentre randomized controlled trial ‘RETRO’. The study observational period was 12 months. Patients in the trial had to be in stable remission (DAS28-ESR<2.6) for a minimum of 6 months and were randomized into 3 different treatment arms: continuation of treatment, tapering by 50% or a gradual tapering until discontinuation [2]. IgA ACPA concentrations were measured with an enzyme-linked immunosorbent assay on CCP2-pre-coated plates.Results:60% of patients had IgG-ACPA. IgA ACPA levels were higher among the IgG-ACPA-positive patients (median 4.7 versus 2.24 µg/ml, p<0.0001). Baseline IgA1 and 2 ACPA levels were not different between patients who had a flare later on in the study period and those remaining in remission, showing no predictive value for flare development. However, the percentage of IgA2 in ACPA was correlating with the first registered DAS28 after flare (r=0.36, p=0.046). After the 12 months study period, IgA2 ACPA as well as IgA2% ACPA decreased significantly in patients who remained in stable remission by 17.5% (median, p<0.0001) and 13.6% (p=0.0006), respectively. By contrast, there was no significant change in IgA2 ACPA levels over time in patients who developed a flare. IgA1 ACPA levels remained stable over time. Disease management strategies did not seem to influence IgA ACPA levels in a specific way, as baseline levels were similar between patients on biological and conventional DMARDs and changes in levels after 12 months did not depend on the assignment to either of the study arms.Conclusion:Neither IgA1 nor IgA2 ACPA levels were predictive of flare development or associated with treatment strategies (though rituximab, JAK-inhibitors and abatacept were not amongst treatment options). However, in patients remaining in sustained remission after 1 year a decrease in IgA2 and IgA2% ACPA was observed and IgA2% ACPA was associated with DAS28 score registered after flare. This could be an indication towards ACPA of IgA2 isotype contributing to the severity of flare, alongside other factors, and its reduction being associated with a prolonged state of remission.References:[1]Steffen U, Koeleman CA, Sokolova MV, et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun 11, 120 (2020).[2]Haschka J, Englbrecht M, Hueber AJ, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 75:45-51 (2016).Disclosure of Interests:None declared

P0582MAGNESIUM TREATMENT IN PREECLAMPSIA SHOULD BE TARGETED TO SERIC LEVELS TO AVOID TOXICITY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Afonso Santos ◽  
Eunice Cacheira ◽  
Sílvia Coelho ◽  
Paulo Telles Freitas
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Platelet Count ◽  
Adverse Effects ◽  
Adverse Events ◽  
Magnesium Sulfate ◽  
Hellp Syndrome ◽  
Fetal Death ◽  
Composite Outcome ◽  
The Impact

Abstract Background and Aims Preeclampsia is potentially serious complication of pregnacy and frequently requires admission in ICU. Management of this condition involves treatment with magnesium sulfate to prevent progression to eclampsia or even more adverse outcomes such as maternal or fetal death. However the exact dose of magnesium needed is still to be determined and few studies have analyzed the impact of this therapheutic intervention in women admitted in intensive care units, in terms of outcomes and adverse effects. Herein, we present a series of patients diagnosed with preeclampsia, including its most severe presentations with eclampsia or HELLP syndrome, admitted in an intensive care unit. Method Demographic, clinical and laboratorial data of women admitted between January-2016 and December-2018 to the Polyvalent Intensive Care Unit (ICU) of Hospital Fernando Fonseca, a tertiary Hospital in Portugal, with the diagnosis of preeclampsia, were retrospectively collected. Diagnosis of preeclampsia, HELLP syndrome and eclampsia were performed according to the ISSHP criteria (2004). Acute Kidney Injury (AKI) was defined according to the KDIGO criteria. The study was approved by the Ethical Committee of the institution. Results 42 patients were included, 52.3% (n=22) diagnosed as non-severe preeclampsia; 31% (n=13) as HELLP syndrome and 16.7% (n=7) as eclampsia. Mean age at presentation was 29.6±6.6 years old, with 52,4% (n=22) caucasian and 47.6% (n=20) black. Most patients were admitted in ICU in post-partum period, after cesarian delivery in 95.2% (n=40). Seven patients (16.7%) had a previous diagnosis of hypertension; 11.9% (n=5) were obese; none has previous chronic kidney disease. At presentation, most patients diagnosed with preeclampsia had three diagnostic criteria (28.6%, n=12), including hypertension. Renal dysfunction was found in 80.9% (n=34) of patients, with proteinuria &gt;200mg/dL in 69% (n=29) and AKI in 19% (n=8). Mean Hb of 11.1±2.1g/dL, with median platelet count of 126000/uL (IQR 72000-201500) and median LDH of 388mg/dL (IQR 240-773). Pre-partum magnesium sulfate treatment was initiated in 78.6% (n=33) of patients, but only 2.4% (n=1) had previous magnesemia levels determination. During the stay in ICU, daily levels of seric magnesium levels were obtained, with the highest median values found at day one after admission. Adverse events related to hypermagnesemia (bradipnea) occurred in 50% (n=21) of patients. In six patients (14.3%), treatment was stopped because of high levels of magnesemia or adverse events. 14.3% (n=6) progressed to eclampsia and fetal death occured also in 14.3% (n=6). Maternal deaths did not occur. By logistic binary regression we found out that weight was an independent risk factor for the development of the composite outcome of eclampsia or fetal death, when adjusted to age, race, AKI, hemoglobin, platelet count, ALT, LDH, serum albumin and proteinuria. (p=0.04). However, when Magnesium was included in the analysis, all variables lost significance. An association between SOFA and SAPS scores and the occurrence of the composite outcome has been found (p= 0.03 and p=0.019, respectively). Conclusion Most patients with preeclampsia received treatment with magnesium sulfate without previous measurement of serum levels. Bradipnea occurred in 50% of cases and treatment had to be stooped in almost 15%. Nevertheless, magnesium levels were not independently associated with the composite outcome of fetal death or eclampsia. Future studies should evaluate if a dose adjusted to a specific target of magnesium seric level could be associated with less adverse effects while still reducing the risk associated with preeclampsia.

Mixed Treatment Comparison of the Treatment Discontinuations of Biologic Disease-Modifying Antirheumatic Drugs in Adults with Rheumatoid Arthritis

2012 ◽  
Vol 46 (11) ◽  
pp. 1491-1505 ◽  
Author(s):  
Rishi J Desai ◽  
Richard A Hansen ◽  
Jaya K Rao ◽  
Tania M Wilkins ◽  
Elizabeth A Harden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Meta Analysis ◽  
Mixed Treatment Comparison ◽  
Disease Modifying Antirheumatic Drugs ◽  
Antirheumatic Drugs ◽  
Biologic Dmards ◽  
Treatment Comparison ◽  
Mixed Treatment ◽  
Disease Modifying

BACKGROUND: Introduction of biologic disease-modifying antirheumatic drugs (DMARDs) has considerably changed treatment options for rheumatoid arthritis (RA) over the past decade. Very little information is available on comparative discontinuation rates of the biologics. OBJECTIVE: To compare treatment discontinuations for 9 biologic DMARDs in adults with RA. METHODS: We searched electronic databases through May 2012 to retrieve randomized controlled trials (RCTs) of patients with RA that compared biologic DMARDs with placebo or another biologic DMARD. The primary outcome was treatment discontinuation during the blinded phase of the trials, measured as overall withdrawals, withdrawals resulting from lack of efficacy, and withdrawals resulting from adverse events. Random-effects meta-analysis estimated the effect size for individual agents, and adjusted indirect comparisons were made between biologics using mixed treatment comparisons (MTC) meta-analysis. RESULTS: Forty-four trials were included in the analysis. In comparison with placebo, biologics were less likely to be withdrawn because of lack of efficacy (OR 0.22, 95% CI 0.17 to 0.27) and more likely to be withdrawn because of an adverse event (OR 1.41, 95% CI 1.16 to 1.70). Based on the MTC, certolizumab had the most favorable overall withdrawal profile, followed by etanercept and rituximab. Certolizumab had lower relative withdrawal rates resulting from lack of efficacy than adalimumab, anakinra, and infliximab. Anakinra had higher relative withdrawal rates resulting from lack of efficacy than most other biologics. Certolizumab and infliximab had more, while etanercept had fewer, withdrawals because of adverse events than most other drugs. CONCLUSIONS: Based on MTC using data from RCTs, differences in discontinuation rates were observed, generally favoring certolizumab, etanercept, and rituximab over other biologic DMARDs. These potential differences need to be further explored in head-to-head trials or well-conducted observational studies.

scholarly journals The Use of Tocilizumab in Combination with Methotrexate in Indonesian Rheumatoid Arthritis Patients (PICTURE INA Study)

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Bambang Setyohadi ◽  
Harry Isbagio ◽  
Rachmat Gunadi Wachjudi ◽  
Joewono Soeroso ◽  
Handono Kalim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Disease Activity ◽  
Severe Disease ◽  
Inadequate Response ◽  
Das28 Score ◽  
Serious Adverse Events ◽  
Biologic Dmards ◽  
Low Disease Activity ◽  
Study Visit

Background Aim of this research is to assess the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) in Indonesian patients with moderate to severe active rheumatoid arthritis (RA) who have an inadequate response to non-biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in  Indonesian male or female patients aged ≥ 18 years old, with a diagnosis of RA for > 6 months based on ACR 1987 revised criteria with moderate to severe disease activity (DAS28 score > 3.2) after ≥ 12 weeks of non-biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous (IV), every 4 weeks for a total of 6 infusion in combination with oral MTX (10−25 mg) every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state (DAS28 < 3.2), percentage of patients achieving reduction > 1.2 point of DAS28, percentage of patients achieving remission (DAS28 < 2.6), and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100% patients reached low disease activity (DAS28 ≤ 3.2) at last study visit (week 24) and clinically significant improvement (reduction at least 1.2 units) at every visit in DAS28, both for ITT or PP patients. Remission (DAS28 < 2.6) was observed in 82.1% (ITT patients) and 93.1 % (PP patients) on last study visit. ACR20, ACR50, and ACR70 were achieved in 20%, 34%, and 34% (ITT patients), and 7%, 24%, and 62% (PP patients) on week 24. There were 3 out of 39 patients (7.69%) with adverse events (AE) and serious adverse events (SAE) that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction (30.7%), hypercholesterolemia (23.1%), followed by arthralgia (20.5%) Twelve percent of patients needed dose modification due to elevated liver enzyme (elevated ALT/SGPT level).Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non- biologic DMARD nonresponsive RA patients of PICTURE INA study.   Keywords: Rheumatoid Arthritis, Tocilizumab, DMARD, DAS28

scholarly journals Obesity reduces the real-world effectiveness of cytokine-targeted but not cell-targeted disease-modifying agents in rheumatoid arthritis

Rheumatology ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 1916-1926 ◽  
Author(s):  
Martin Schäfer ◽  
Yvette Meißner ◽  
Jörn Kekow ◽  
Sylvia Berger ◽  
Sven Remstedt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Effectiveness ◽  
Negative Impact ◽  
Daily Practice ◽  
Observation Time ◽  
Tnf Inhibitors ◽  
Biologic Dmards ◽  
Drug Effectiveness ◽  
Disease Modifying Agents ◽  
The Impact

Abstract Objectives The effectiveness of TNF inhibitors in RA has been shown to be affected by obesity. No such effect has been found for abatacept and rituximab, while for tocilizumab results are ambiguous. Additionally, it remains unresolved whether sex is an effect modifier for obesity. We investigated the impact of obesity on the drug effectiveness of conventional synthetic or biologic DMARDs, taking into account potential sex-specific differences. Methods Data from 10 593 RA patients included in the German observational cohort study Rheumatoid Arthritis: oBservation of BIologic Therapy (RABBIT) since 2009 were analysed. Patients had to have a BMI ≥18.5 kg/m2, at least one follow-up and 6 months of observation time. The influence of obesity on drug effectiveness was investigated by regression analysis, adjusting for potential confounders. Results Obesity had a negative impact on improvement in the DAS with 28 joints using ESR as an inflammation marker of –0.15 (95% CI: –0.26; –0.04) units for women receiving conventional synthetic DMARDs, –0.22 (95% CI: –0.31; –0.12) units for women receiving TNF inhibitors, –0.22 (95% CI: –0.42; –0.03) units for women receiving tocilizumab and –0.41 (95% CI: –0.74; –0.07) units for men receiving tocilizumab. Overall, no negative obesity effects on the effectiveness of rituximab and abatacept were found. Conclusion Obesity has a negative impact on the effectiveness of cytokine-targeted but not cell-targeted therapies in daily practice, affecting more outcomes and therapies in women than in men. Overall, no effects of obesity on treatment effectiveness were found for rituximab and abatacept.

Population-based patterns of palliative systemic therapy use in elderly patients with metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9547-9547
Author(s):  
Matthew Chan ◽  
Gillian Gresham ◽  
Winson Y. Cheung
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Systemic Therapy ◽  
Early Treatment ◽  
Cox Regression ◽  
Young Patients ◽  
Population Based ◽  
Patient Choice ◽  
Advanced Age ◽  
The Impact

9547 Background: Elderly cancer patients are consistently under-represented in clinical trials, which may lead to under-treatment. Our aims were to 1) determine the impact of advanced age on use of palliative systemic therapy in mCRC, 2) examine the reasons for treatment choices and 3) compare adverse events and treatment discontinuations in elderly vs young patients. Methods: All patients diagnosed with mCRC from 2006 to 2007 and referred to any 1 of 5 regional cancer centers in British Columbia, Canada were reviewed. Summary statistics were used to describe treatment patterns between elderly patients (EP; >/=70 years) and young patients (YP; <70 years). Cox regression models that adjusted for age and confounders were used to determine the effect of systemic therapy on overall survival (OS). Results: We identified 1,013 patients: median age was 67 years (range 23-93); 42% were elderly and 58% were young; 57% were men; and 66% had ECOG 0/1. Compared to YP, fewer EP were offered systemic therapy (46 vs 76%, p<0.001). Among those treated, EP were less likely than YP to be given combination chemotherapy (47 vs 81%, p<0.001) and bevacizumab (19 vs 47%, p<0.001). Most common reasons for no treatment were similar in EP and YP: patient choice (32% for both), poor ECOG (18% of EP and 16% of YP), and significant comorbidities (11% for both). Advanced age alone was also cited as a reason among EP (7%) for not receiving therapy. In the subset that was treated, risk of adverse events (24 vs 14%, p=0.24) and early treatment discontinuations (14 vs 13%, p=0.88) were comparable between EP and YP, respectively. Receipt of systemic therapy was associated with improved OS in both the elderly (HR for death 0.45, 95% CI 0.37-0.56, p<0.001) and the young (HR for death 0.43, 95% CI 0.35-0.53, p<0.001), regardless of age (p interaction of age and treatment >0.05). Conclusions: In this population-based cohort of mCRC, EP were more likely to receive no treatment, monotherapy rather than combination therapy, or a regimen without bevacizumab. In carefully selected EP, however, it appears that rate of adverse events, frequency of early treatment discontinuations, and magnitude of survival benefit from systemic therapy were comparable to YP.

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