scholarly journals Real-world comparative effectiveness and safety of tofacitinib and baricitinib in patients with rheumatoid arthritis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Naoki Iwamoto ◽  
Shuntaro Sato ◽  
Shota Kurushima ◽  
Toru Michitsuji ◽  
Shinya Nishihata ◽  
...  

Abstract Objective To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. Methods A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. Results The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, −0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. Conclusions Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.

2021 ◽  
Author(s):  
Naoki Iwamoto ◽  
Shuntaro Sato ◽  
Shota Kurushima ◽  
Toru Michitsuji ◽  
Shinya Nishihata ◽  
...  

Abstract Objective: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting.Methods: A total of 242 patients with RA who were treated with tofacitinib (n=161) or baricitinib (n=81) were enrolled. To avoid confounding, we performed propensity score matching based on multiple baseline characteristic variables, and then 80 baricitinib-treated patients and 57 tofacitinib-treated patients were extracted for direct comparison. Their clinical disease activity and AEs were evaluated for 24 weeks. Results: The mean DAS28-ESR change from baseline to 24 weeks were 1.60 (tofacitinib) and 1.46 (baricitinib). There was no significant difference in the clinical response between two groups. The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in both groups, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was also associated. Conclusions: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, the influence of clinical characteristics on the treatment response differed. Direct comparison provides useful information to optimal use of JAK inhibitors in real-world settings.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 581.3-581
Author(s):  
N. Iwamoto ◽  
T. Suzuki ◽  
A. Okada ◽  
K. Fujikawa ◽  
T. Aramaki ◽  
...  

Background:Tofacitinib is a non-selective first-generation JAK inhibitor and baricitinib was approved for the treatment of Rheumatoid arthritis several years after approve of tofacitinib. Randomized controlled trials have shown good treatment response for RA in these two drugs. However, the evaluation of these two drugs in real-world setting have been rarely reported, moreover, until now, no published data of a direct comparison among JAK inhibitors in RA have been available.Objectives:To compare the efficacy and safety of the JAK inhibitors tofacitinib and baricitinib in patients with rheumatoid arthritis (RA) by using propensity score matching in a real-world setting.Methods:A total of 242 patients with RA who were treated with tofacitinib (n=161) or baricitinib (n=81) were enrolled. To avoid confounding, we performed propensity score matching based on multiple baseline characteristic variables, and then 80 baricitinib-treated patients and 57 tofacitinib-treated patients were extracted for the direct comparison. A mixed effect model with a repeated measures analysis of variance (ANOVA) was performed to ascertain whether there were significant differences in clinical efficacy between the two treatment groups during the treatment period.Finally, We evaluated the predictive factor of clinical responses by performing univariate and multivariable logistic regression analyses.Results:The mean delta disease activity scores (DAS)28-ESR from baseline to 6 months were −1.60 (tofacitinib) and −1.46 (baricitinib). The remission rate defined by the DAS28-ESR at 24 weeks were 21.1% (tofacitinib) and 25.0% (baricitinib). There was no significant difference in the clinical response between the baricitinib-treated and tofacitinib-treated groups. Although there was no significant difference, the concomitant use of methotrexate (MTX) showed better clinical efficacy in the cases of baricitinib treatment as compared with in the case of tofacitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response differed. The concomitant use of oral steroid was independently associated with the achievement of DAS-low disease activity in both groups, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used and the DAS28-ESR at the time of initiation were associated with DAS-low disease activity.Conclusion:This study indicate that tofacitinib and baricitinib had comparable efficacies and safety profiles in a real-world setting. However, the influence of clinical characteristics on the treatment response differed between these two drugs. Direct comparison between two JAK inhibitors provide useful information to optimal use of JAK inhibitors in real-world settings.Disclosure of Interests:None declared


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Ulu ◽  
F. Demir ◽  
T. Coşkuner ◽  
Ş. Çağlayan ◽  
B. Sözeri

Background:The TNF-α inhibitor adalimumab is a biological disease modifying anti-rheumatic drug (bDMARD) that has been used in different rheumatic diseases with a resistant course. ABP-501 is a biosimilar product (BP) of adalimumab, recently approved by the FDA and EMA. To our knowledge, there is no study assess the efficacy and safety of these two molecules on pediatric patients.Objectives:We aimed to compare the efficacy and safety of the original and biosimilar adalimumab (ABP-501) molecules in childhood rheumatic diseases.Methods:This non-interventional, retrospective, single-centre analysis carried out in Umraniye Training and Resrach Hospital, Pediatric Rheumatology Clinic, Istanbul, Turkey. The study group consisted of patients who were followed due to chronic rheumatic disease between January 1, 2016 and June 1, 2020, and received reference or biosimilar adalimumab therapy for at least three months. Demographic and clinical data of patients were collected at baseline, 3rd, 6th, and 12th months of treatment. Disease activity assessment was made with JADAS-27 in JIA patients, with SUN criteria in uveitis patients, and with Behçet’s Disease Activity Index in BD patients. Efficacy and safety of treatments were compared between reference and biosimilar adalimumab groups.Results:A total of 89 patients (65 with original and 24 with biosimilar molecule) treated with adalimumab, were included in the study. There were 45 female and 44 male in the study, and the median age at the initiation of the adalimumab was 166 months (min-max: 36-231). Of the 89 patients evaluated, the primary diagnoses of 62 were juvenile idiopathic arthritis, 13 were idiopathic uveitis, eight were Behçet’s disease, three were Blau syndrome, two were chronic recurrent multifocal osteomyelitis and one was Vogt-Koyanagi-Harada syndrome. 63 of the patients were biologic-naïve, and 13 were switched from etanercept, 11 from infliximab, and two from other bDMARDs. The median exposure time of adalimumab was 16 months (min-max:3-70) in RP and 14.5 months (min-max: 3-23) in BP. All patients had active disease before treatment. In the group treated with RP, inactive disease was achieved in 60%, 76.6% and 87.2% of the patients at the 3rd, 6th and 12th months, respectively. Also, inactive disease was achieved in 62.5%, 78.2% and 78.2% of the patients at the 3rd, 6th and 12th months in the group treated with BP, respectively. There was no statistically significant difference in efficacy between the groups at the 3rd, 6th and 12th months (p=0.83, 0.07 and 0.32). Serious adverse events were seen in one patient in each groups (lymphoma in RP group, tuberculous meningitis in BP group). Non-serious adverse events were observed in eight patients (12.3%) in the RP group and in two patients (8.3%) in the BP group, without statistically significant difference between groups (p=0.86).Conclusion:No significant difference was observed between the biosimilar adalimumab ABP-501 and RP adalimumab in terms of efficacy and safety.References:[1]Renton, William D et al. Pediatr Rheumatol Online J. 2019;17(1):67.[2]Lovell DJ, Ruperto N, Goodman S, et al. N Engl J Med. 2008;359(8):810-820.[3]Kingsbury, Daniel J et al. Clin Rheumatol 2014;33(10):1433-41.Disclosure of Interests:None declared


2018 ◽  
Vol 2018 ◽  
pp. 1-14
Author(s):  
Weihao Chen ◽  
Yurong Wang ◽  
Qiuer Liang ◽  
Yunfei Cai ◽  
Xudong Chen ◽  
...  

Objectives. To evaluate the efficacy and safety of Aidi injection (ADI) combined with transcatheter arterial chemoembolization (TACE) for primary hepatic carcinoma (PHCC). Methods. We conducted a literature search in EMBASE, PubMed, CENTRAL, MEDLINE, CNKI, Wanfang, and VIP databases from the earliest possible year to April 2018. Randomized controlled trials (RCTs) involving ADI combined with TACE versus TACE alone for patients with PHCC were included. The Cochrane Risk of Bias tool was applied for quality assessment. Results. 22 studies involving 1611 participants were included. The clinical response rate (RR = 1.28, 95% CI: 1.17-1.40; P < 0.00001), KPS score (RR = 1.78, 95% CI: 1.59-2.00; P < 0.00001), survival rate (RR = 1.27, 95% CI: 1.16-1.39; P < 0.00001), immune function (MD = 1.24, 95% CI: 0.98-1.51; P < 0.00001), and adverse effects (RR = 0.62, 95% CI: 0.57-0.68; P < 0.00001) of ADI plus TACE showed significant difference when compared with TACE alone. Conclusions. ADI combined with TACE in the treatment of PHCC improved the clinical response rate and safety compared to TACE alone. However, due to poor methodological quality of many of the included RCTs, more rigorously designed and large-scale RCTs are warranted to examine this beneficial effect in the future.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 458.1-458
Author(s):  
R. Yokochi ◽  
H. Tamai ◽  
T. Kido ◽  
Y. Yagyu ◽  
D. Waki ◽  
...  

Background:Several previous observational studies have suggested that patients with anti-Ro/SSA antibody-positive rheumatoid arthritis (RA) may respond poorly to treatment, including tumor necrosis factor inhibitors1. However, its influence on methotrexate (MTX) treatment, which is the anchor drug of treat-to-target strategy in RA treatment, remains unclear.Objectives:We compared the clinical response to MTX in both anti-Ro/SSA antibody-positive and -negative patients with MTX-naiive RA and investigated the reasons for the difference in response.Methods:We recruited 210 consecutive patients with RA who were newly started on MTX in this retrospective cohort study. The effect of the presence of anti-Ro/SSA antibodies on achieving low disease activity (LDA) of DAS28-CRP at six months after initiating MTX was investigated by using logistic regression analysis. CDAI, SDAI, concomitant using DMARDs and painkillers, patient’s and evaluator’s VAS, tender joint counts, and swollen joint counts at six months were also compared between the anti-Ro/SSA-positive patients and -negative patients. Missing data were imputed by using multiple imputations before multivariate analysis.Results:32 anti-Ro/SSA antibody-positive patients and 178 anti-Ro/SSA antibody-negative patients were included. The rate of achieving DAS28-LDA at six months was significantly lower in the anti-Ro/SSA antibody-positive patients than those in the anti-Ro/SSA antibody-negative patients (56.2% versus 75.8%, P=0.03). in the logistic regression analysis, the presence of anti-Ro/SSA antibodies was an independent negative predictor for achieving DAS-28-LDA at six months (OR:0.431, 95%CI: 0.190-0.978, P=0.044) (Table1). Anti-Ro/SSA antibody-positive patients had significantly higher patient’s VAS at six months (median [IQR]: 22 [15-41] vs 19 [5-30], P=0.038), and prescribed NSAIDs (37.5% vs 18.0%, P=0.018). CDAI and SDAI after six months were not significantly different between the group.Conclusion:The presence of anti-Ro/SSA antibodies might be one of the predictive factors for the insufficient response to treat to target strategy in RA treatment. Residual pain was suspected as one of the mechanisms contributing to the lesser clinical response of MTX in anti-Ro antibody-positive RA.References:[1]Ran Matsudaira wt al. J Rheumatol 2011;38(11):2346-54Table 1.Logistic regression analysis for the rate of achieving DAS28 low disease activity at six months.Risk factor Odds ratio95%CIP valueAge at onset0.9930.968-1.0180.586Sex (woman)0.6430.300-1.3840.258RF-positive1.9620.853-4.5110.112ACPA-positive0.5520.225-1.3510.192Anti-Ro/SSA antibody-positive0.4310.190-0.9780.044Disclosure of Interests:None declared


2021 ◽  
pp. jrheum.201135
Author(s):  
Sae Ochi ◽  
Fumitaka Mizoguchi ◽  
Kazuhisa Nakano ◽  
Yoshiya Tanaka

Objective Increasing numbers of patients are developing rheumatoid arthritis (RA) at an older age, and optimal treatment of elderly-onset RA (EORA) patients is attracting greater attention. This study aimed to analyze the efficacy and safety of biological/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) in EORA and non-EORA elderly patients. Methods A cohort of RA patients treated with b/tsDMARDs were retrospectively analyzed. Among patients who were ≥60 years old, those who developed RA after age 60 years were categorized as EORA, while others were categorized as non-EORA elderly. Disease activity were compared between the EORA and non-EORA elderly groups. Results In total, 1,040 patients were categorized as EORA and 710 as non-EORA elderly. There were not significant differences in characteristics at baseline between the two groups. The proportion of patients with low and high disease activity was comparable at week 2, 22 and 54 between in the EORA and the non-EORA elderly group. There was not significant difference in reasons of the discontinuation of b/tsDMARDs between the two groups. Elderly onset did not affect changes in CDAI and HAQ-DI as well as reasons of the discontinuation between the two groups. The trajectory analysis on CDAI-responses to b/tsDMARDs for 54 weeks identified three response patterns. The proportions of patients categorized into each group and CDAI-response trajectories to b/tsDMARDs were very similar between EORA and non-EORA elderly patients. Conclusion CDAI response patterns to b/tsDMARDs and hazard ratio of adverse events were similar between EORA and non-EORA elderly patients.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Stefan Siebert ◽  
Elisa Gremese ◽  
Paul Bergmans ◽  
Kurt de Vlam ◽  
Beatriz Joven-Ibáñez ◽  
...  

Abstract Background The additional benefit of methotrexate (MTX) as a concomitant treatment in PsA has not been fully elucidated for TNF inhibitors (TNFi) and no real-world data on this currently exist for ustekinumab (UST). We investigated the additive effect of MTX on the ability to reach composite treatment targets beyond monotherapy with UST or TNFi, and the ability to improve patient-reported outcomes in a real-world clinical setting in 8 European countries. Methods The PsABio study (NCT02627768) evaluates persistence, effectiveness and tolerability of 1st, 2nd or 3rd-line UST or TNFi in patients with PsA. Proportions of patients reaching minimal disease activity (MDA)/very low disease activity (VLDA) and clinical Disease Activity in Psoriatic Arthritis (cDAPSA) low disease activity (LDA) or remission, as well as the patient acceptable symptom state (PASS; score ≤4) of the 12-item Psoriatic Arthritis Impact of Disease questionnaire (PsAID-12) were evaluated. Here we present 6-month follow-up data using intention to treat (ITT) analysis; patients who stopped/switched initial treatment were imputed as non-responders. The effect of MTX co-therapy was investigated within UST and TNFi cohorts, as well as between the cohorts, using multivariate logistic regression including interaction terms, and propensity score (PS) analysis to adjust for imbalanced, potentially prognostic, baseline covariates. Results Of 930 patients, data was available for 868 ITT patients, including patients who switched/stopped before 6 months (UST: n = 28/426 [6.6%], TNFi: n = 44/442 [10.0%]). At baseline there were no relevant differences in demographics and disease activity, however there were significant differences in skin involvement as well as csDMARD and NSAID exposure. Co-therapy with MTX did not increase the likelihood of achieving any of the outcomes in either the UST or TNFi cohorts (Table 1). After PS adjustment, co-treatment with MTX did not influence treatment effects differently when added to UST compared with TNFi. concomitant use of csDMARDs other than MTX yielded very similar results. Conclusion In a real-world setting, concomitant treatment with MTX in addition to UST or TNFi was not associated with enhanced effects across a broad variety of disease outcomes, including disease activity, disease impact, and skin involvement within or between treatment cohorts, after PS adjustment for baseline confounders. Disclosures S. Siebert: Consultancies; AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, Novartis. Grants/research support; Pfizer, Janssen, BMS, Celgene, UCB, Boehringer Ingelheim. E. Gremese: Consultancies; AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, Pfizer. P. Bergmans: Shareholder/stock ownership; Johnson & Johnson. Other; Employee of Janssen. K. de Vlam: Consultancies; Johnson & Johnson. B. Joven-Ibáñez: Member of speakers’ bureau; Celgene, Novartis, MSD, Pfizer, AbbVie, Janssen. G. Katsifis: None. T.V. Korotaeva: Consultancies; Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, UCB, Lilly, Novartis-Sandoz. W. Noël: Other; Employee of Janssen. C. Selmi: None. P.P. Sfikakis: None. P. Smirnov: Other; Employee of Janssen. E. Theander: Other; Employee of Janssen. M.T. Nurmohamed: Grants/research support; Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Lilly, Sanofi, Celgene. L. Gossec: Honoraria; AbbVie, Celgene, Janssen, Lilly, Novartis-Sandoz, Pfizer, Sanofi, UCB. Grants/research support; Pfizer. J.S. Smolen: Consultancies; AbbVie, Amgen, AstraZeneca, Astro, Celgene, Celtrion, GlaxoSmithKline, ILTOO Pharma, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB. Grants/research support; AbbVie, Janssen, Lilly, MSD, Pfizer, Roche.


Lupus ◽  
2019 ◽  
Vol 28 (10) ◽  
pp. 1189-1196 ◽  
Author(s):  
N Poomsalood ◽  
P Narongroeknawin ◽  
S Chaiamnuay ◽  
P Asavatanabodee ◽  
R Pakchotanon

Objective The objective of this study was to determine the association between disease activity status and health-related quality of life (HRQoL) in systemic lupus erythematosus (SLE) patients. Methods SLE patients in an out-patient clinic during the previous 12 months were included in the study. The Systemic Lupus Erythematosus-specific Quality-of-Life questionnaire (SLEQoL) was administered at the last visit. Disease activity status was determined retrospectively during the previous year. The categories of disease activity status were defined as: clinical remission (CR): clinical quiescent disease according to Systemic Lupus Erythematosus Disease Activity Index 2000, prednisolone ≤ 5 mg/day; low disease activity (LDA): SLEDAI-2K (without serological domain) ≤ 2, prednisolone ≤ 7.5 mg/day; and non-optimally controlled status: for those who were not in CR/LDA. Immunosuppressive drugs (maintenance dose) and antimalarials were allowed. Prolonged CR or LDA was defined as those with sustained CR or LDA for at least one year. The association between disease activity status and HRQoL was assessed by using regression analysis adjusting for other covariates. Results Of 237 SLE patients, 100 patients (42.2%) achieved prolonged CR, 46 patients (19.4%) achieved prolonged LDA and 91 patients (38.4%) were not in CR/LDA. Non-CR/LDA patients had significantly higher total SLEQoL score and in all domains compared to CR/LDA patients. No significant difference in SLEQoL domain scores was found between CR and LDA groups. Multivariable analysis revealed that non-CR/LDA was positively associated with SLEQoL score compared with CR/LDA (β 20.02, 95% confidence interval (CI) 6.81–33.23, p < 0.003). Moreover, non-CR/LDA was at a higher risk of impaired QoL (SLEQoL score > 80) compared with CR (hazard ratio 3.8; 95% CI 1.82–7.95; p < 0.001). However, there was no significant difference between CR and LDA in terms of SLEQoL score or impaired QoL. Other factors associated with higher SLEQoL score were damage index (β 9.51, 95% CI 3.52–15.49, p = 0.002) and anemia (β 24.99, 95% CI 5.71–44.27, p = 0.01). Conclusion Prolonged CR and LDA are associated with better HRQoL in SLE patients and have a comparable effect. Prolonged CR or optional LDA may be used as the treatment goal of a treat to target approach in SLE.


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