scholarly journals AB0256 BARICITINIB (BARI) VERSUS BIOLOGICS IMPACT ON STEROID TAPERING IN RHEUMATOID ARTHRITIS (RA)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1154-1155
Author(s):  
L. Cometi ◽  
C. Bruni ◽  
L. Tofani ◽  
G. Tesei ◽  
F. Nacci ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Randomized Clinical Trials ◽  
Functional Disability ◽  
Disease Duration ◽  
Kinase Inhibitor ◽  
Real Life ◽  
Janus Kinase ◽  
Functional Improvement ◽  
Research Support

Background:Biologic and target synthetic disease modifying anti-rheumatic drugs (bDMARDs and tcDMARDs) are recommended to control RA disease activity, pain and steroid use. Following randomized clinical trials (RCTs) and their post-hoc analyses, the Janus Kinase Inhibitor tsDMARDs BARI was superior to reference bDMARD Adalimumab in reducing disease activity, pain and functional disability. In addition, BARI monotherapy also determined more significant pain reduction and functional improvement when compared to Tocilizumab monotherapy (3).Objectives:to confirm RCT results in a real-life clinical setting, with focus on disease activity, pain, functional disability and steroid tapering, when comparing BARI to bDMARDs for the treatment of active RA.Methods:RA patients starting BARI or a bDMARD for active RA were retrospectively evaluated from June 2019 to June 2020. Disease activity (DAS28CRP, SDAI, CDAI), pain visual analogic scale (pain_VAS), functional disability (HAQ) assessments and mean prednisone dosage (pred_dose) were collected at baseline (BL), 3 months (3M) and 6 months (6M) after BARI/bDMARD initiation. The changes of the outcome measures were evaluated between BL-3M, 3M-6M and BL-6M, as well as between BARI and bDMARDs groups. Finally, we assessed the variables associated with prednisone tapering in the whole population.Results:90 out of 100 RA patients evaluated (baseline: age 57±12 years, disease duration 131±100 months, DAS28PCR 4.8±1.0, pain_VAS 61±23 mm, prednisone dose 5.5±5.3 mg) were eligible for the study; 49 received BARI and 41 bDMARDs (17 abatacept, 12 TNF inhibitors, 11 tocilizumab, 1 rituximab). At BL, the two groups did not differ statistically in terms of age, sex, disease duration, disease activity, pain_VAS, previous bDMARD failure or ts/bDMARD naive, concomitant conventional synthetic DMARDs treatment, pred_dose. Both BARI and bDMARDs determined a significant reduction in activity scales and HAQ when comparing BL-3M and BL-6M, with only pain_VAS and pred_dose showing a significant decrease in the 3M-6M interval. When comparing the two groups, BARI showed a significantly higher reduction of pred_dose (-3.2±5.1 vs -1.7±3.7 mg at BL-3M, and -4.1±5.3 vs -1.9±4.6 mg at BL-6M), which was not significant after adjusting for BL pred_dose. No other difference was seen when the two groups, including the numerically higher reduction of pain_VAS in the BARI group (-29±28 vs -20±27 mm at BL-3M and -35±25 vs -30±28 mm at BL-6M comparison). The analysis of the predictors for steroid tapering (Δmean_pred) in the two intervals, showed that BL DAS28PCR, DAS28PCR BL-3M change and BL pred_dose were associated with BL-3M Δmean_pred, while 3M pain_VAS and 3M pred_dose were associated with 3M-6M Δmean_pred.Conclusion:Although limited by the small samples and the retrospective nature, our real-life comparison shows similar efficacy of BARI and bDMARDs in terms of disease activity control, functional disability and pain. In addition, the treatment with BARI or bDMARD did not influence the steroid tapering, which was driven mostly by its initial dose, disease activity and pain. Larger real-life multi-center studies are warranted to confirm our results.References:[1]Taylor PC et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662.[2]Fautrel B et al. Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM. J Clin Med. 2019 Sep 5;8(9):1394.[3]Fautrel B et al. Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment withDisclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Fondazione Italiana Ricerca sull’Artrite (FIRA), Gruppo Italiano lotta alla Sclerodermia (GILS), New Horizon Fellowship, European Scleroderma Trials and Research (EUSTAR) group, Foundation for Research in Rheumatology (FOREUM)., Lorenzo Tofani: None declared, Giulia Tesei: None declared, Francesca Nacci: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Marco Matucci-Cerinic Speakers bureau: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Consultant of: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Grant/research support from: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly,

AB0179 BEYOND DISEASE ACTIVITY, PAIN, “TIME” AND “TIMING” ACCOUNT FOR DISABILITY IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS FROM A REAL-LIFE COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1389-1389
Author(s):  
H. Assunção ◽  
A. R. Prata ◽  
M. Luis ◽  
L. Brites ◽  
J. Dinis de Freitas ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Disease Duration ◽  
Univariate Analysis ◽  
Real Life ◽  
Severe Disability ◽  
Self Perception ◽  
Modifiable Factors ◽  
Time To Diagnosis

Background:Patients with rheumatoid arthritis (RA) suffer from joint pain, stiffness and fatigue and are therefore limited in their physical activities. Since functional disability is a major determinant of quality of life in patients with RA, an optimized approach should focus on the maintenance of functional ability.Objectives:To evaluate self-reported disability in RA patients and to identify its influencing clinical and demographic factors in a real-life cohort of patients with RA.Methods:Cross-sectional study of consecutive patients with RA fulfilling the ACR/EULAR 2010 and/or ACR 1987 RA classification criteria, followed in a Portuguese tertiary care centre. Variables collected included socio-demographic and clinical variables (disease duration; time from symptoms onset to diagnosis, classified as short (≤ 2 years) and long (> 2 years); time of diagnosis, categorised as <2000, 2000-2009, ≥2010); DAS28-CRP-3V and its individual components; pain assessed through visual analogue scale (0-100 mm) and self-perception of anxiety/ depression through EQ5D dimension 5. Disability was assessed through Health Assessment Questionnaire (HAQ) score and categorised as none-to-mild (<1) or moderate-to-severe (1-3). Comparison between groups was assessed through chi-square or T-student test, as adequate. Variables with p<0.1 and others clinically relevant in the researcher’s perspective were included in a multivariable logistic regression model. Previously to the analysis, all the assumptions were verified. Given the implementation of new strategies regarding diagnosis and treatment of RA in the last decade, a subgroup analysis was performed for patients with diagnosis performed after 2010).Results:A total of 251 patients were included (78.9% female, aged 62.0±12.1 years, disease duration 16.7±11.2 years), with a mean DAS28-CRP-3V of 2.24 ±0.87, with 65.3% being in remission or low disease activity. The mean HAQ score was 1.2±0.8. Over half of the patients (56.2%) reported moderate-to-severe disability. In the univariate analysis, moderate-to-severe disability was more frequent in female patients (60.6% vs 39.6%, p<0,006), in patients with moderate-to-severe self-perception of anxiety/depressive symptoms (67.2% vs 44.2%, p<0.001) and in patients with diagnosis before the year 2000, 2000-2009 than ≥2010 (71.4% vs 63.1% vs 36.7%; p< 0.001). In addition, patients with moderate-to-severe disability tended to be older (65.05 vs 57.98, p<0,001), to have longer disease duration (20.07 vs 12.39, p <0.001), to report more pain (VAS 58.08 vs 28.62, p<0.001) and to have higher disease activity (2.48 vs 1.95, p=0.001). In the multivariable analysis, pain (OR=1.04; 95%CI 1.03-1.06, p<0.001), disease activity (OR=1.51; 95%CI 1.01-2.26, p=0.049), and time of diagnosis (OR=0.553, 95%CI 0.38 -0.81, p=0.002) remained as independent factors associated with moderate-to-severe disability (R2: 0.40, p<0,001). In the subgroup of patients diagnosed after 2010, a longer time to diagnosis (>2 years) (OR=7.97, 95%CI 1.88-34.06; p=0.005) and pain (OR=1.05, 95%CI 1.03-1.08; p<0,001) remained as independent factors (R2= 0.44, p=<0.001).Conclusion:Functional disability remains a major problem in our patients with RA, despite clinical remission. Beyond non-modifiable factors, disease activity and pain are associated with higher disability. Moreover, in the subgroup of patients diagnosed after 2010 a long time to diagnosis was the major predictor of disability. However, a large variance of the reported functional disability remains unexplained. Hence, other factors should be properly evaluated in our patients in order to achieve a more holistic approach aiming at reducing functional disability.Disclosure of Interests:Helena Assunção: None declared, Ana Rita Prata: None declared, Mariana Luis: None declared, Luisa Brites: None declared, João Dinis de Freitas: None declared, Flavio Costa: None declared, Stefanie Silva: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Catia Duarte: None declared

scholarly journals Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts

2019 ◽  
Vol 8 (10) ◽  
pp. 1548 ◽  
Author(s):  
Mueller ◽  
Hasler ◽  
Popp ◽  
Mattow ◽  
Durmisi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Randomized Clinical Trials ◽  
Liver Enzymes ◽  
Real Life ◽  
Gastrointestinal Symptoms ◽  
Janus Kinase ◽  
Secondary Outcome ◽  
Low Disease Activity

: Introduction: Tofacitinib is an oral JAK inhibitor indicated for the treatment of rheumatoid arthritis (RA). The efficacy and safety of tofacitinib have been shown in several randomized clinical trials. The study presented here aimed to assess the clinical tolerability and effectiveness of tofacitinib among RA patients in real life. Methods: Consecutive patients between January 2015 and April 2017 with RA who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 criteria were included in a prospectively designed analysis of retrospective data. Patients were initiated on tofacitinib 5 mg bid. The primary objective was to analyze the safety of tofacitinib in a real-life cohort. Safety was assessed by the reasons to stop tofacitinib during follow up and changes of liver enzymes, hemoglobin, and creatinine. The secondary outcome was to analyze the frequency of and time to achieve low disease activity (LDA) and remission as defined by 28 joint count disease activity score (DAS28). Results: A total of 144 patients were treated with tofacitinib. A total of 84.9% of patients were pre-exposed to at least one biological agent. The average DAS28 at the initiation of tofacitinib was 4.43. A total of 50.0% of patients were positive for rheumatoid factor and 49.0% for ACPA. The mean follow up was 1.22 years (range 10d–3.7a) after initiation of tofacitinib treatment. A total of 94 (64.4%) patients remained on tofacitinib during follow-up. The average time to stop tofacitinib was 190.0 days. Reasons to stop tofacitinib were: insufficient response (n = 23), gastrointestinal symptoms (n = 18), infection (n = 5), myalgia (n = 2), remission (n = 2), headache (n = 2), cough, blue finger syndrome, intolerance, heartburn, psoriasis, and increased liver enzymes (all n = 1). Increased alanine amino transferase (ALAT) or aspartate amino transferase (ASAT) > 2× upper limit of normal (ULN) were detected in 3.3% and 4.4% of patients, respectively. Hemoglobin decrease of >10% was detected in 15.1% of the patients and decreased lymphocytes <500/μL in 3.4%. An increase of creatinine >20% was detected in 9.4% of patients. A total of 62.9% and 50.0% of the patients achieved low disease activity (LDA) or remission after a median of 319 and 645 days, respectively. These rates were significantly higher in patients naïve to biologic agents as compared to patients pre-exposed to biologics (LDA: naïve 100% 92 d, pre-exposed 57.0% 434 d, p ≤ 0.001; remission: naïve 86.7% 132 d, pre-exposed 44.1%, 692 d, p = 0.001). Conclusions: Tofacitinib is a safe and effective treatment option for patients with RA. Tofacitinib may induce high rates of LDA and remission in patients with active disease, even after the use of one or more biologics, though the rate appeared higher in patients naïve to biologics. Tofacitinib may be a valuable option in a treat-to-target approach. Our data demonstrate that Janus kinase (JAK) inhibitors are safe and efficacious in real life patients.

scholarly journals AB0330 HIGH REMISSION RATES IN RA – REAL LIFE DATA FROM BARITICINIB

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1463.2-1464
Author(s):  
S. Bayat ◽  
K. Tascilar ◽  
V. Kaufmann ◽  
A. Kleyer ◽  
D. Simon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cox Regression ◽  
Real Life ◽  
Inadequate Response ◽  
Research Support ◽  
Das 28 ◽  
Patient Reported ◽  
One Year

Background:Recent developments of targeted treatments such as targeted synthetic DMARDs (tsDMARDs) increase the chances of a sustained low disease activity (LDA) or remission state for patients suffering rheumatoid arthritis (RA). tsDMARDs such as baricitinib, an oral inhibitor of the Janus Kinases (JAK1/JAK2) was recently approved for the treatment of RA with an inadequate response to conventional (cDMARD) and biological (bDMARD) therapy. (1, 2).Objectives:Aim of this study is to analyze the effect of baricitinb on disease activity (DAS28, LDA) in patients with RA in real life, to analyze drug persistance and associate these effects with various baseline characteristics.Methods:All RA patients were seen in our outpatient clinic. If a patient was switched to a baricitinib due to medical reasons, these patients were included in our prospective, observational study which started in April 2017. Clinical scores (SJC/TJC 76/78), composite scores (DAS28), PROs (HAQ-DI; RAID; FACIT), safety parameters (not reported in this abstract) as well as laboratory biomarkers were collected at each visit every three months. Linear mixed effects models for repeated measurements were used to analyze the time course of disease activity, patient reported outcomes and laboratory results. We estimated the probabilities of continued baricitinib treatment and the probabilities of LDA and remission by DAS-28 as well as Boolean remission up to one year using survival analysis and explored their association with disease characteristics using multivariable Cox regression. All patients gave informed consent. The study is approved by the local ethics.Results:95 patients were included and 85 analyzed with available follow-up data until November 2019. Demographics are shown in table 1. Mean follow-up duration after starting baricitinib was 49.3 (28.9) weeks. 51 patients (60%) were on monotherapy. Baricitinib survival (95%CI) was 82% (73% to 91%) at one year. Cumulative number (%probability, 95%CI) of patients that attained DAS-28 LDA at least once up to one year was 67 (92%, 80% to 97%) and the number of patients attaining DAS-28 and Boolean remission were 31 (50%, 34% to 61%) and 12(20%, 9% to 30%) respectively. Median time to DAS-28 LDA was 16 weeks (Figure 1). Cox regression analyses did not show any sufficiently precise association of remission or LDA with age, gender, seropositivity, disease duration, concomitant DMARD use and number of previous bDMARDs. Increasing number of previous bDMARDs was associated with poor baricitinib survival (HR=1.5, 95%CI 1.1 to 2.2) while this association was not robust to adjustment for baseline disease activity. Favorable changes were observed in tender and swollen joint counts, pain-VAS, patient and physician disease assessment scores, RAID, FACIT and the acute phase response.Conclusion:In this prospective observational study, we observed high rates of LDA and DAS-28 remission and significant improvements in disease activity and patient reported outcome measurements over time.References:[1]Keystone EC, Taylor PC, Drescher E, Schlichting DE, Beattie SD, Berclaz PY, et al. Safety and efficacy of baricitinib at 24 weeks in patients with rheumatoid arthritis who have had an inadequate response to methotrexate. Annals of the rheumatic diseases. 2015 Feb;74(2):333-40.[2]Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. The New England journal of medicine. 2016 Mar 31;374(13):1243-52.Figure 1.Cumulative probability of low disease activity or remission under treatment with baricitinib.Disclosure of Interests:Sara Bayat Speakers bureau: Novartis, Koray Tascilar: None declared, Veronica Kaufmann: None declared, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Johannes Knitza Grant/research support from: Research Grant: Novartis, Fabian Hartmann: None declared, Susanne Adam: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

scholarly journals SAT0039 ADAPTIVE DEEP LEARNING FOR THE PREDICTION OF INDIVIDUAL DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 950.1-950
Author(s):  
M. Hügle ◽  
G. Kalweit ◽  
U. Walker ◽  
A. Finckh ◽  
R. Muller ◽  
...  
Keyword(s):  
Neural Network ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Deep Neural Networks ◽  
Disease Duration ◽  
Research Support ◽  
Disease Characteristics ◽  
Individual Disease ◽  
Active Disease ◽  
Research Grant

Background:Rheumatoid arthritis (RA) lacks reliable biomarkers that predict disease evolution on an individual basis, potentially leading to over- and undertreatment. Deep neural networks learn from former experiences on a large scale and can be used to predict future events as a potential tool for personalized clinical assistance.Objectives:To investigate deep learning for the prediction of individual disease activity in RA.Methods:Demographic and disease characteristics from over 9500 patients with 65.000 visits from the Swiss Quality Management (SCQM) database were used to train and evaluate an adaptive recurrent neural network (AdaptiveNet). Patient and disease characteristics along with clinical and patient reported outcomes, laboratory values and medication were used as input features. DAS28-BSR was used to predict active disease and future numeric individual disease activity by classification and regression, respectively.Results:AdaptiveNet predicted active disease defined as DAS28-BSR>2.6 at the next visit, with an overall accuracy of 75.6% and a sensitivity and specificity of 84.2% and 61.5%, respectively. Apart from DAS28-BSR, the most influential characteristics to predict disease activity were joint pain, disease duration, age and medication. Longer disease duration, age >50 or antibody positivity marginally improved prediction performance. Regression allowed forecasting individual DAS28-BSR values with a mean squared error of 0.9.Conclusion:Deep neural networks have the capacity to predict individual disease outcome in RA. Low specificity remains challenging and might benefit from alternative input data or outcome targets.References:[1] Hügle M, Kalweit G, Hügle T, Boedecker J. A Dynamic Deep Neural Network For Multimodal Clinical Data Analysis. Be Publ Stud Comput Intell Springer Verl. 2020.Figure 1.Examples of true disease activity and corresponding predictions of AdaptiveNet by regression analysis. Predictions are made step to step from the current to next visit.Disclosure of Interests:Maria Hügle Paid instructor for: Lilly, Gabriel Kalweit: None declared, Ulrich Walker Grant/research support from: Ulrich Walker has received an unrestricted research grant from Abbvie, Consultant of: Ulrich Walker has act as a consultant for Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, Sanofi, and ThermoFisher, Paid instructor for: Abbvie, Novartis, and Roche, Speakers bureau: Abbvie, Actelion, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, and ThermoFisher, Axel Finckh Grant/research support from: Pfizer: Unrestricted research grant, Eli-Lilly: Unrestricted research grant, Consultant of: Sanofi, AB2BIO, Abbvie, Pfizer, MSD, Speakers bureau: Sanofi, Pfizer, Roche, Thermo Fisher Scientific, Rudiger Muller Consultant of: AbbVie, Nordic, Sandoz, Almut Scherer: None declared, Joschka Boedecker: None declared, Thomas Hügle Grant/research support from: Abbvie, Novartis, Consultant of: Abbvie, Pfizer, Novartis, Roche, Lilly, BMS

scholarly journals AB0337 TOFACITINIB MONOTHERAPY OR COMBINED WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS SHOW SIMILAR RETENTION OVER FOUR YEARS. REPORT FROM RHUMADATA ®

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1467.1-1467
Author(s):  
D. Choquette ◽  
L. Bessette ◽  
L. Choquette Sauvageau ◽  
I. Ferdinand ◽  
B. Haraoui ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Real World ◽  
Treatment Initiation ◽  
Retention Rate ◽  
Janus Kinase ◽  
P Value ◽  
Research Support ◽  
Medication Discontinuation ◽  
Kaplan Meier

Background:Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2].Objectives:To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA).Methods:Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts.Results:Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318).Conclusion:Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX.References:[1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012.[2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9].Rheumatol Ther. 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4.Disclosure of Interests:Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme,UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared

scholarly journals Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2020-218412
Author(s):  
Roy M Fleischmann ◽  
Ricardo Blanco ◽  
Stephen Hall ◽  
Glen T D Thomson ◽  
Filip E Van den Bosch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Kinase Inhibitor ◽  
Activity Index ◽  
Disease Activity Index ◽  
Initial Therapy ◽  
Janus Kinase ◽  
Treat To Target ◽  
Efficacy And Safety ◽  
Insufficient Response

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

scholarly journals Long-term effectiveness and safety of infliximab, golimumab and golimumab-IV in rheumatoid arthritis patients from a Canadian prospective observational registry

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Proton Rahman ◽  
Philip Baer ◽  
Ed Keystone ◽  
Denis Choquette ◽  
Carter Thorne ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Events ◽  
Disease Activity ◽  
Randomized Clinical Trials ◽  
Disease Duration ◽  
Routine Care ◽  
Treatment Modalities ◽  
The Mean ◽  
Over Time

Abstract Background Long-term clinical registries are essential tools to evaluate new therapies in a patient population that differs from those in randomized clinical trials. The objectives are to describe the profile of rheumatoid arthritis (RA) patients treated with anti-TNF agents in Canadian routine care. Methods RA patients eligible for treatment with Infliximab (IFX), golimumab (GLM) or intravenous golimumab (GLM-IV) as per their respective Canadian product monographs were enrolled into the BioTRAC registry between 2002 and 2017. Study visits occurred at baseline and every 6 months thereafter. Effectiveness was assessed by changes in disease activity. Safety was evaluated by the incidence of adverse events (AEs) and drug survival. Results Of the 890 IFX-, 530 GLM- and 157 GLM-IV-treated patients, the proportion of females ranged from 77.0–86.6%, the mean ages from 55.8–57.7 and the mean disease duration from 6.5–8.6 years. A significant decrease in baseline disease duration and disease activity parameters (DAS, TJC, SJC, HAQ, AM stiffness, MDGA, PtGA, CRP, ESR) was observed over time. Treatment with IFX, GLM- and GLM-IV significantly improved all disease parameters over time. The incidence of AEs was 105, 113 and 82.6 /100 PYs and the incidence of SAEs was 11.7, 11.2 and 4.68 /100 PYs for IFX, GLM- and GLM-IV-treated patients, respectively. Conclusion Differences in baseline characteristics between patients treated with an anti-TNFs over time shows the evolution of treatment modalities over time. All treatments significantly reduced disease activity and improved functionality in a similar fashion. The incidence of adverse events was consistent with the safety profiles of IFX and GLM. Trial registration ClinicalTrials.gov Identifier: NCT00741793 (Retrospectively registered on August 26, 2008).

THU0201 LONG-TERM SAFETY AND EFFECTIVENESS OF UPADACITINIB OR ADALIMUMAB IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS AT 72 WEEKS FROM THE SELECT-COMPARE STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 323-323
Author(s):  
R. Fleischmann ◽  
I. H. Song ◽  
J. Enejosa ◽  
E. Mysler ◽  
L. Bessette ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Activity Index ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Research Support ◽  
Hepatic Disorder ◽  
Compare Study

Background:In the SELECT-COMPARE study in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), upadacitinib (UPA), a Janus Kinase (JAK) 1-selective inhibitor, showed significant improvements in treatment of signs and symptoms when compared to placebo (PBO) and adalimumab (ADA) up to 48 weeks.1Objectives:To report safety and efficacy of UPA vs ADA up to 72 weeks in patients with RA from the ongoing long-term extension (LTE) of SELECT-COMPARE.Methods:Patients were randomized to once daily (QD) UPA 15 mg, PBO, or ADA 40 mg every other week, with all patients continuing background MTX. The study was double-blind for 48 weeks. Between Weeks 14-26, patients were rescued (from PBO to UPA, UPA to ADA, or ADA to UPA) if there was <20% improvement in tender/swollen joint count at Weeks 14/18/22 or if Clinical Disease Activity Index (CDAI) was >10 at Week 26; all PBO patients who were not rescued were switched to UPA at Week 26. Patients continued UPA or ADA in a blinded manner until the last patient completed the Week 48 visit; patients received open-label treatment thereafter. Study visits occurred at Week 60, 72, and every 12 weeks thereafter. Treatment-emergent adverse events (TEAEs) per 100 patient years (PY) were summarized up to December 26, 2018. Efficacy was analyzed by randomized group.Results:In total, 651, 651 and 327 patients were randomized at baseline to receive UPA, PBO, and ADA, respectively. Subsequently, 252 patients were switched from UPA to ADA, 159 were switched from ADA to UPA, and all PBO patients were switched to UPA. 1403 patients entered the LTE at Week 48 (UPA: 1091 [565 switched from PBO; 66 rescued from ADA; 460 on continued UPA]; ADA: 312 [110 rescued from UPA; 202 on continued ADA]). The cumulative exposures were 1396.7 and 515.1 PYs for UPA and ADA, respectively. UPA + MTX was generally well-tolerated as assessed by the frequency of AEs, including serious AEs, AEs leading to discontinuation of study drug, and AEs of special interest ([AESIs] including serious and opportunistic infections, malignancy, adjudicated major adverse cardiac events or venous thromboembolism; Figure 1). The event rates of AESIs were generally comparable between UPA + MTX and ADA + MTX, except for herpes zoster, lymphopenia, hepatic disorder, and CPK elevation, which were numerically higher with UPA + MTX. At both Weeks 60 and 72, significantly greater proportions of patient receiving UPA + MTX achieved ACR20/50/70 (P ≤.01/.001/.001), low disease activity (P ≤.001) and remission (P ≤.001) compared to those receiving ADA + MTX; Figure 2). Similarly, improvements in pain and function were significantly greater in the UPA vs ADA group through Week 72 (P ≤.01).Conclusion:The safety profile for UPA + MTX was consistent with that reported previously and with the integrated Phase 3 safety analysis.1,2UPA + MTX maintained significantly higher levels of clinical response, including remission compared to ADA + MTX through Week 72.References:[1]Fleischmann R, et al.Annals of the Rheumatic Diseases.2019;78:744-745.[2]Cohen SB, et al. Thu0167.Annals of the Rheumatic Diseases. 2019;78:357.Disclosure of Interests: :Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jeffrey Enejosa Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Eduardo Mysler Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer., Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Roche, Eli Lilly, Novartis, Janssen, Sanofi, and Pfizer, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Andrew Ostor Consultant of: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Speakers bureau: MSD, Pfizer, Lilly, Abbvie, Novartis, Roche, Gilead and BMS, Jerzy Swierkot Grant/research support from: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Consultant of: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Speakers bureau: AbbVie, Sandoz, Pfizer, Roche, BMS, UCB, MSD, Accord, Janssen, Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

SAT0555 MUSCULOSKELETAL ULTRASOUND IN MONITORING RESPONSE TO JAKi IN RHEUMATOID ARTHRITIS PATIENTS: RESULTS FROM A LONGITUDINAL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1235-1236
Author(s):  
E. Cipriano ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
C. Garufi ◽  
I. Duca ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Longitudinal Study ◽  
Disease Activity ◽  
Power Doppler ◽  
Real Life ◽  
Research Support ◽  
Prospective Longitudinal Study ◽  
Inflammatory Score ◽  
Inflammatory Status ◽  
Prospective Longitudinal

Background:Therapeutic approach of rheumatoid arthritis (RA) patients has been enriched by the introduction of small molecules. In particular Jak inhibitors (JAKi), baricitinib and tofacitinib, demonstrated their efficacy in patients naïve or resistant to biological treatments in randomized controlled trials. Moreover, these drugs seem to be able to prevent radiographic progression. To date few data are available from the real life context. Ultrasonographic (US) assessment has became a valid imaging tool in the management of RA patients in clinical practice, allowing the evaluation of joint inflammatory status. Together with clinimetric assessment, US could provide a comprehensive assessment of drug response.Objectives:In the present study we aimed at assessing the early response to JAKi treatment by using musculoskeletal US.Methods:In this prospective longitudinal study, we collected data about all consecutive active RA patients starting treatment with JAKi. RA was diagnosed according to the 2010 ACR/EULAR criteria. At each visit, clinical and laboratory data were collected in a standardized and computerized form, including demographics, past medical history, co-morbidities, previous and concomitant treatments. According with study protocol, all patients underwent clinical and US assessment at the following time-points: baseline (T0), 4 weeks (T1) and 12 weeks (T2). Clinical evaluation included tender and swollen joint counts (0-28), patients global health assessment. C-reactive protein (CRP) levels were registered and disease activity was calculated by disease activity score (DAS) in 28 joints by using CRP (DAS28-CRP). A systematic multiplanar grey-scale and power Doppler (pD) US examination was performed by using MyLab Eight Exp Machine (Esaote, Florence, Italy) at level of 22 joints (bilateral I-V metacarpophalangeal, I-V proximal interphalangeal, wrist). According with OMERACT definitions (1) we assessed the presence of synovial effusion, hypertrophy and pD, that were scored according to a semi-quantitative scale (0-3). A total US inflammatory score (0-198) was obtained by their sum.Results:We enrolled 91 patients [F/M 77/14; median age 60.0 years (IQR 15.5); median disease duration 144 months (IQR 126)]. Of these patients, 54 (59.3%) were treated by baricitinib and the remaining 37 by tofacitinib. At baseline we found a median US inflammatory score of 20 (IQR 18.7) and a median DAS28-CRP of 5.0 (IQR 1.56). US assessment demonstrated significant reduction in the median values of inflammatory score already at T1 [median 13 (IQR 14.7), p<0.0001], that was maintained at T2 [median 10 (IQR 11), p<0.0001]. These results are represented in figure 1. Similar to US inflammatory score, a significant reduction was registered for DAS28-CRP median values [T1 3.5 (IQR 1.73), p<0.0001; T2 3.3 (IQR 1.8), p<0.0001]. No significant differences were found when subgrouping patients according with different JAKi drug, in terms US and clinimetric assessment.Conclusion:In the present study, specifically designed to evaluate the US-detected efficacy of JAKi in RA patients, we demonstrated in a real life setting a significant, early and sustained improvement of inflammatory joint status.References:[1]Wakefield et al, J Rheumatol 2005Disclosure of Interests:enrica cipriano: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Cristina Garufi: None declared, Ilaria Duca: None declared, Silvia Mancuso: None declared, cristiano alessandri Grant/research support from: Pfizer, Manuela Di Franco: None declared, Roberta Priori: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Carlo Perricone: None declared, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi

scholarly journals Comparative Analyses of Serological Biomarkers and Disease Characteristics between Elderly-onset and Younger-onset Rheumatoid Arthritis

2021 ◽  
Vol 16 (1) ◽  
pp. 237-245
Author(s):  
Rajalingham Sakthiswary ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Disease Duration ◽  
Severe Disease ◽  
Age At Onset ◽  
Health Assessment ◽  
Joint Damage ◽  
Study Data ◽  
Elderly Onset

The onset of rheumatoid arthritis (RA) may occur any time after the age of 16 years. The purpose of this study was to compare the clinical and serological differences between elderly onset RA (EORA); which is begins at the age of 60 and above, with younger onset RA (YORA). A total of 69 EORA and 82 YORA female patients were enrolled in this study. Data on medications, disease duration, age at onset, disease activity at onset and laboratory parameters were collected by reviewing the medical records. All patients had their blood samples taken for serum anticyclic citrulinated peptide (anti-CCP), IgA rheumatoid factor (RF), IgM RF and IgG RF. Besides, the subjects were assessed for their radiographic joint damage based on Modified Sharp Score (MSS) and functional disability based on the Health Assessment Questionnaire-disability Index (HAQ-DI) scores. Despite comparable disease duration and frequency of seropositivity, the YORA group had significantly higher disease activity at onset of the disease (p=0.009). In keeping with this finding, the YORA group had more severe joint damage based on radiographic assessment (MSS scores of 17.49+19.04 versus 10.04+12.79). The YORA group had significantly higher levels of IgA RF and anti-CCP with p-values of 0.035 and 0.002, respectively. Our findings suggest that YORA is associated with more severe disease, worse radiographic joint damage and higher levels of anti-CCP and IgA RF.

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