Persistence to Biologic Therapy among Patients with Spondyloarthritis: An Observational Study using the OPAL Dataset

2021 ◽  
pp. jrheum.201551
Author(s):  
Hedley Griffiths ◽  
Tegan Smith ◽  
Christopher Mack ◽  
Jo Leadbetter ◽  
Belinda Butcher ◽  
...  
Keyword(s):  
Disease Activity ◽  
Treated Group ◽  
Treatment Persistence ◽  
Kaplan Meier ◽  
Time Period ◽  
Sampling Window ◽  
Biologic Dmard ◽  
Australian Cohort ◽  
Third Line Therapy ◽  
Third Line

Objective To describe the treatment response and persistence to biologic DMARD (bDMARD) therapy in patients with ankylosing spondylitis (AS) in a real-world Australian cohort. Methods This was a retrospective, non-interventional cohort study that extracted data for patients with AS from the Optimising Patient outcomes in Australian rheumatology (OPAL) dataset for the period Aug-2006 to Sep-2019. Patients were classified as either bDMARD initiators if they commenced a bDMARD during the sampling window, or bDMARD naïve if they did not. Results were summarised descriptively. Treatment persistence was calculated using Kaplan-Meier methods. Differences in treatment persistence were explored using log-rank tests. Results 5048 patients with AS were identified. 2597 patients initiated bDMARDs and 2451 remained bDMARD naïve throughout the study window. Treatment with first, second and third line bDMARDs significantly reduced disease activity. Median persistence on first line bDMARDs was 96 months (95% CI 85 to 109), declining to 19 months (95% CI 16 to 22) in second line, and 14 months (95% CI 11 to 18) in third line therapy. Median persistence was longest for the golimumab treated group in all lines of therapy and shortest for the etanercept group. Differences in persistence rates according to the time-period that bDMARDs were prescribed (pre-and post-2012) were also seen for etanercept and adalimumab. Conclusion In this cohort all bDMARDs effectively reduced disease activity. Patients remained on their first bDMARD longer than subsequent agents. Median persistence was longest for the golimumab treated group in all lines of therapy and shortest for the etanercept group.

scholarly journals Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 138
Author(s):  
Matteo Santoni ◽  
Francesco Massari ◽  
Sergio Bracarda ◽  
Giuseppe Procopio ◽  
Michele Milella ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Body Mass ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
Third Line Therapy ◽  
Third Line

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, p < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.

scholarly journals Prospective Outcomes of Second Line Therapy in Acute Gvhd: Six Month Freedom from Treatment Failure and Day 28 Response in a Multicentre Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3408-3408
Author(s):  
Rohini Radia ◽  
Arun Alfred ◽  
Matthew P. Collin ◽  
Maria H Gilleece ◽  
James E Griffin ◽  
...  
Keyword(s):  
Partial Response ◽  
Median Survival ◽  
Research Funding ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Third Line Therapy ◽  
Third Line ◽  
Steroid Refractory

Abstract Introduction Acute graft-versus-host disease (aGVHD) is a significant cause of mortality post allogeneic stem cell transplantation (SCT). First line therapy is corticosteroid based for patients with aGVHD ≥grade (Gd) II. Steroid refractory (SR) aGVHD is associated with a dismal prognosis. Although experimental therapeutics is an unmet need, there is no recent prospective real world data to establish a benchmark for outcomes of best available therapy. We undertook a prospective observational multi-centre international clinical trial of outcomes of second line therapy of steroid refractory aGVHD. The aim was to measure recently defined endpoints including Day 28 (D28) overall response rate (ORR), and 6 month freedom from treatment failure (6mFFTF; defined as a patient (pt) being alive, without relapse of underlying disease or addition of new systemic therapy for aGVHD, prior to the development of chronic(c) GVHD. Methods Data was collected prospectively in a longitudinal observational study in patients starting second line therapy for SR aGVHD. Twelve UK and 2 US sites participated. Adult pts with Gd II-IV aGVHD refractory to corticosteroids were enrolled within 5 days of starting second line therapy. Modified Glucksberg criteria were used to grade aGVHD. Expert panel consensus recommendations (Martin et al 2009) were used for complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD) and progressive disease (PD). Kaplan-Meier survival curves and log rank tests for comparison were done on Prism7. Results Between 2014-2018, 64pts were enrolled; 4pts were excluded due to incomplete data. Baseline characteristics of the cohort are outlined in Table 1. GVHD prophylaxis varied according to centre. Forty-seven percent had T depletion; 32% ATG and 25% Alemtuzumab. GVHD was donor lymphocyte infusion (DLI) induced in 7%. At start of second line therapy,5% had Gd I, 27% Gd II and 68% Gd III-IV aGVHD. All patients had received corticosteroids at a minimum dose of 1mg/kg. Second line therapies varied, 60% received ECP and 40% non-ECP therapy including anti-TNF-alpha antibodies (20%), mycophenolate mofetil (MMF) (8%), mesenchymal stem cells (4%) and 'other' (8%). The cumulative incidence of 6mFFTF was 32% (n=19), with 68% (n=41) failing to meet the 6mFFTF endpoint. The causes of failure were, addition of third line therapy in 40% (n=24), relapse 8%(n=5), cGVHD 7% (n=4) and death 13% (n=8). The 6m incidence of death was 45% (n=27); death due to GVHD 30%, infection 8% and relapse 7%. D28 responses were: 56% ORR (8% CR, 28% VGPR, 20% PR), 13% SD, 18% PD and 13% died before D28. Using Kaplan-Meier analysis, median OS was 7.3m with a median follow up of 1 year. The overall cumulative incidence of death was 63% (n=38); GVHD was the leading cause of death 40%, infection 8% and relapse 8%. D28 ORR was associated with a significantly improved median OS not reached versus (vs) 5.2m (p=0.03) in pts who had SD or PD at D28. In pts that achieved 6mFFTF, median survival beyond 6m was not yet reached vs median survival of 3.9m in those that did not achieve 6mFFTF (p=0.0004). The trend was for a longer median OS of 8.2m in the ECP arm vs 5.3m in non ECP (p=0.79). GVHD Gd at start of second line therapy was associated with a longer median survival, not reached in Gd II cohort vs 5.7m in Gd III-IV cohort (p=0.25). Discussion Our multi-centre prospective study illustrates 'real-life' data of clinical outcomes in pts starting second line therapy for SR aGVHD. Median survival from start of second line therapy was 7.3m with a high mortality rate of 63%. D28 ORR was 56% but only 32% met the composite 6mFFTF endpoint, although both outcomes predicted survival. The leading cause for failure of 6mFFTF was starting third line therapy which may be subject to clinician bias, however the 6m mortality was 45%, thus pts went on to die after failing for another cause. This data can be used as a contemporary data while planning studies of experimental intervention vs. best available therapy. Disclosures Radia: Mallinckrodt: Research Funding. Alfred:Mallinckrodt: Speakers Bureau. Dignan:Mallinckrodt: Research Funding, Speakers Bureau. Jagasia:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees.

scholarly journals H2-antagonist in IgE-mediated type I hypersensitivity reactions: what literature says so far?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Matteo Borro ◽  
Simone Negrini ◽  
Andrew Long ◽  
Sharon Chinthrajah ◽  
Giuseppe Murdaca
Keyword(s):  
Receptor Antagonist ◽  
Inflammatory Responses ◽  
Type I ◽  
Line Therapy ◽  
H2 Antagonist ◽  
Amino Acid Histidine ◽  
Third Line Therapy ◽  
Ige Mediated ◽  
Third Line ◽  
Type I Hypersensitivity

AbstractHistamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.

scholarly journals POS0407 PROTEOMICS ANALYSIS COMPARING THE MODE OF ACTION OF UPADACITINIB BETWEEN NON-BIOLOGIC-DMARD-IR AND BIOLOGIC-DMARD-IR PsA PATIENTS IDENTIFIES DISTINCT PATHOGENIC PATHWAYS IN THE SELECT-PsA 1 AND SELECT-PsA 2 PHASE 3 STUDIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 433.1-433
Author(s):  
T. Sornasse ◽  
J. Anderson ◽  
K. Kato ◽  
A. Lertratanakul ◽  
I. McInnes ◽  
...  
Keyword(s):  
Disease Activity ◽  
Clinical Response ◽  
Rheumatic Diseases ◽  
Inadequate Response ◽  
Protein Biomarkers ◽  
Research Support ◽  
Positive Correlation ◽  
Disease Biology ◽  
Biologic Dmard ◽  
Favorable Clinical Response

Background:Treatment of non-biologic-DMARD-IR1 (DMARD-IR) and biologic-DMARD-IR2 (bio-IR) PsA patients with upadacitinib (UPA) at 15 mg QD, an oral JAK1 selective inhibitor, resulted in significant improvement in signs and symptoms compared to placebo.Objectives:Using a pre-defined set of inflammation-related plasma protein biomarkers (pBM), to explore immunological pathway modulation by UPA 15 mg QD in PsA patients with active disease despite treatment with non-biologic or biologic DMARDs in the context of clinical response vs. non-response to treatment.Methods:Patients from the SELECT-PsA 1 (DMARD-IR) and the SELECT-PsA 2 (bio-IR) studies were randomly selected (PBO, n=100; UPA 15 mg QD, n=100 for each study). The levels of 92 inflammation related protein biomarkers (pBM) were analyzed using a multiplexed Proximity Extension Assay platform in plasma samples collected at baseline, week 2, and 12; change from baseline in protein levels was expressed as Log2 Fold Change; a Repeated Measure Mixed Linear Model was used to identify pBM modulated by UPA compared to Baseline, and those differentially modulated between responders (R) and non-responders (NR) according to ACR50, PASDAS Minimal Disease Activity, and PASI75 at week 12. Correlation of disease activity measures with relative levels of pBM were derived using Pearson’s correlation; PASI score was transformed as Log10 (x+1) prior to the analysis. Functional pathway prediction was performed in silico with a commercial distributed software.Results:At baseline, the relative levels of 37 pBM correlated with at least one baseline disease activity measure, with a marked positive correlation of IL6 with musculoskeletal end points (PASDAS and DAS28CRP), and a strong positive correlation of IL20, IL17A, IL17C, and TGFA with baseline PASI.At the single pBM-level, treatment with UPA 15 mg QD resulted in a down modulation of pBM associated with T cells, myeloid cells, and IFN-, IL6-, and TNF-related pathways in both DMARD-IR and bio-IR PsA patients. Overall effects of UPA on single pBMs were broadly similar between DMARD-IR and bio-IR patients. However, analysis of pBMs differentially modulated by UPA in R vs NR indicated that favorable clinical response (achievement of ACR50, PASDAS MDA, and PASI75) in DMARD-IR patients was associated with the down modulation of pBMs predicted to be linked to IFN, IL10, IL17, IL22, and IL27 pathways; while favorable clinical response in bio-IR patients was associated with the down modulation of multiple pBM predicted to be linked to the IL17, IL23, and IL1 pathways.Conclusion:UPA effects in both DMARD-IR and bio-IR PsA patients likely stem from the direct and indirect inhibition of multiple biological pathways belonging to the adaptive and innate immune systems. Responder/Non-Responder analysis suggests a possible shift from a TH1 biased biology in DMARD-IR PsA patients to a more TH17 biased biology in bio-IR PsA patients. This apparent change in the disease biology of PsA patients after inadequate response to prior therapy could be attributed to the actual alteration of the disease biology, treatment outcome-based patient selection, or both. Considering the clinical efficacy of UPA in both DMARD-IR and bio-IR PsA patients, this observation highlights the importance of targeting multiple pathways with drugs such as UPA for the treatment of a broad range of PsA patients.References:[1]McInnes, I. et al. Annals of the Rheumatic Diseases 79, 16-17 (2020).[2]Mease, P.J. et al.Annals of the Rheumatic Diseases, annrheumdis-2020-218870 (2020).Acknowledgements:AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship.Disclosure of Interests:Thierry Sornasse Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Apinya Lertratanakul Shareholder of: AbbVie, Employee of: AbbVie, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sun, UCB Pharma, Grant/research support from: AbbVie, Amgen, UCB

scholarly journals POS1021 THE PsABio STUDY IN ITALY: A REAL-WORLD COMPARISON OF THE PERSISTENCE, EFFECTIVENESS AND SAFETY OF USTEKINUMAB AND TUMOUR NECROSIS FACTOR INHIBITORS IN PATIENTS WITH PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 778-779
Author(s):  
E. Gremese ◽  
F. Ciccia ◽  
C. Selmi ◽  
G. Cuomo ◽  
R. Foti ◽  
...  
Keyword(s):  
Adverse Event ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Research Support ◽  
Treatment Persistence ◽  
Low Disease Activity ◽  
Necrosis Factor

Background:There are still unmet needs in the treatment of psoriatic arthritis (PsA), including in terms of treatment persistence, which is a function of effectiveness, safety and patient satisfaction. Ustekinumab (UST) was the first new biologic drug to be developed for the treatment of PsA after tumour necrosis factor inhibitors (TNFi).Objectives:To compare treatment persistence, effectiveness and safety of UST and TNFi in Italian patients within the PsABio cohort.Methods:PsABio (NCT02627768) is an observational study of 1st/2nd/3rd-line UST or TNFi treatment in PsA in 8 European countries. The current analysis set includes 222 eligible patients treated in 15 Italian centres, followed to Month 12 (±3 months). Treatment persistence/risk of stopping was analysed using Kaplan−Meier (KM) and Cox regression analysis. Proportions of patients reaching minimal disease activity (MDA)/very low disease activity (VLDA) and clinical Disease Activity Index for PsA (cDAPSA) low disease activity (LDA)/remission were analysed using logistic regression, including propensity score (PS) adjustment for imbalanced baseline covariates, and non-response imputation of effectiveness endpoints if treatment was stopped/switched before 1 year. Last observation carried forward data are reported.Results:Of patients starting UST and TNFi, 75/101 (74.3%) and 77/121 (63.6%), respectively, persisted with treatment at 1 year. The observed mean persistence was 410 days for UST and 363 days for TNFi. KM curves and PS-adjusted hazard ratios confirmed significantly higher persistence (hazard ratio [95% confidence interval (CI)]) for UST versus TNFi overall (0.46 [0.26; 0.82]; Figure 1). Persistence was also higher for UST than TNFi in patients receiving monotherapy without methotrexate (0.31 [0.15; 0.63]), in females (0.41 [0.20; 0.83]), and in patients with body mass index (BMI) <25 kg/m2 (0.34 [0.14; 0.87]) or >30 kg/m2 (0.19 [0.06; 0.54]). There was no significant difference in persistence between treatments in patients with BMI 25−30 kg/m2. While patients receiving 1st- and 3rd-line UST or TNFi showed similar risk of discontinuation (0.60 [0.27; 1.29] and 0.36 [0.10; 1.25], respectively), patients receiving 2nd-line UST showed better persistence than those receiving 2nd-line TNFi (0.33 [0.13; 0.87]). Other factors added to the PS-adjusted Cox model did not show significant effects. In patients with available follow-up data, the mean (standard deviation) baseline cDAPSA was 26.3 (15.4) for UST and 23.5 (12.3) for TNFi; at 1-year follow-up, 43.5% of UST- and 43.6% of TNFi-treated patients reached cDAPSA LDA/remission. MDA was reached in 24.2% of UST- and 28.0% of TNFi-treated patients, and VLDA in 12.5% of UST- and 10.2% of TNFi-treated patients. After PS adjustment (stoppers/switchers as non-responders), odds ratios (95% CI) at 1 year did not differ significantly between UST and TNFi groups for reaching cDAPSA LDA/remission (1.08 [0.54; 2.15]), MDA (0.96 [0.45; 2.05]) or VLDA (0.98 [0.35; 2.76]). In total, 23 (20.4%) patients reported ≥1 treatment emergent adverse event with UST and 30 (22.2%) with TNFi; 6 (5.3%) and 10 (7.4%) patients, respectively, discontinued treatment because of an adverse event.Conclusion:In the Italian PsABio cohort, UST had better overall persistence compared with TNFi, as well as in specific subgroups: females, patients on monotherapy without methotrexate, with BMI <25 or >30 kg/m2, and patients receiving UST as 2nd-line treatment. At 1 year, both treatments showed similar effectiveness, as measured by cDAPSA responses and MDA/VLDA achievement.Acknowledgements:This study was funded by Janssen. Contributing author: Prof. Piercarlo Sarzi-Puttini, ASST Fatebenefratelli-Sacco, University of Milan, ItalyDisclosure of Interests:Elisa Gremese: None declared, Francesco Ciccia Speakers bureau: AbbVie, Abiogen, Bristol-Myers Squibb, Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Consultant of: Celgene, Janssen, Lilly, Novartis, Pfizer, Roche, Grant/research support from: Celgene, Janssen, Novartis, Pfizer, Roche, Carlo Selmi Speakers bureau: AbbVie, Alfa-Wassermann, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme, Consultant of: AbbVie, Alfa-Wassermann, Amgen, Biogen, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofi-Genzyme, Grant/research support from: AbbVie, Amgen, Janssen, Pfizer, Giovanna CUOMO: None declared, Rosario Foti Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Janssen, Roche, Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Janssen, Roche, Sanofi, Marco Matucci Cerinic Speakers bureau: Actelion, Biogen, Janssen, Lilly, Consultant of: Chemomab, Grant/research support from: MSD, Fabrizio Conti Consultant of: AbbVie, Bristol-Myers Squibb, Galapagos, Lilly, Pfizer, Enrico Fusaro Speakers bureau: AbbVie, Amgen, Lilly, Grant/research support from: AbbVie, Pfizer, Giuliana Guggino Speakers bureau: AbbVie, Celgene, Novartis, Pfizer, Sandoz, Grant/research support from: Celgene, Pfizer, Florenzo Iannone Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, Pfizer, Sanofi, UCB, Andrea Delle Sedie: None declared, Roberto Perricone: None declared, Luca Idolazzi Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Sandoz, Paolo Moscato: None declared, Elke Theander Employee of: Janssen, Wim Noel Employee of: Janssen, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Silvia Marelli Employee of: Janssen, Laure Gossec Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Biogen, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Lilly, Pfizer, Sandoz, Sanofi, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Lilly, MSD, Novartis- Sandoz, Pfizer, Roche, Samsung, Sanofi, UCB, Grant/research support from: AbbVie, AstraZeneca, Lilly, Novartis, Roche.

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 SAT0398 PERSISTENCE OF USTEKINUMAB (UST) OR TNF INHIBITOR (TNFI) TREATMENT IN PSORIATIC ARTHRITIS (PsA): INSIGHTS FROM THE LARGE, PROSPECTIVE, MULTINATIONAL, REAL-WORLD PsABio COHORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1149-1150
Author(s):  
L. Gossec ◽  
S. Siebert ◽  
P. Bergmans ◽  
K. De Vlam ◽  
E. Gremese ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Real World ◽  
Treatment Effect ◽  
Cox Model ◽  
Tnf Inhibitor ◽  
Skin Involvement ◽  
Research Support ◽  
Treatment Persistence ◽  
Kaplan Meier ◽  
Significant Difference

Background:Several biologic DMARDs (bDMARDs) exist for PsA, TNFi and UST being the earliest on European markets. When bDMARDs are insufficiently effective, later-line bDMARDs typically have shorter persistence. Treatment persistence reflects a mix of effectiveness and adverse events (AEs), and persistence data are limited in PsA.Objectives:Comparative analysis of 1-year persistence of UST and TNFi within the prospective PsABio cohort.Methods:PsABio is an observational, multinational study of PsA patients (pts) treated with 1st to 3rd line UST or TNFi at their rheumatologist’s discretion.1Treatment persistence (up to 15 months of follow-up) was defined as time between start of first bDMARD treatment in PsABio, and either stop or switch to another bDMARD, or withdrawal.Persistence of UST and TNFi is shown by Kaplan-Meier curves and compared using Cox regression analysis, with propensity score (PS) to adjust for baseline imbalanced demographic and disease-related covariates (age, sex, bDMARD line, BMI, Clinical Disease Activity index for PSoriatic Arthritis [cDAPSA], 12-item PsA Impact of Disease [PsAID-12], Fibromyalgia Rapid Screening Tool [FiRST] score, co-treatments with MTX, NSAIDs, glucocorticoids, cardiovascular/metabolic comorbidities, dactylitis, enthesitis and body surface area [BSA]). Factors including concomitant MTX use and skin involvement: <3%, 3–10% and >10%, were added to the Cox model to investigate their impact on the PS-adjusted treatment effect.Results:Of 438 and 455 pts who started UST and TNF, respectively, 121 (28%) and 134 (29%) stopped or switched treatment before Month 15, with differences (as expected) according to treatment line (Fig. 1a, b). Reasons for stop/switch were related to safety/AEs in 12% (UST) and 28% (TNFi), and effectiveness (joints, nails or skin) in 77% (UST) and 69% (TNFi) of pts.The observed mean time on drug was 397 days for UST and 385 days for TNFi pts (1st line 410/397 days, 2nd 390/382 days, 3rd 381/338 days). Fig. 1b shows similar persistence for all drugs and treatment lines, except for lower persistence in TNFi 3rd line vs 1st/2nd. In PS-adjusted Cox analysis, no statistically significant difference between UST and TNFi persistence was seen; hazard ratio (HR; 95% CI) for stop/switch bDMARD (UST vs TNFi) was 0.82 (0.60, 1.13). In the model, bDMARD monotherapy (without MTX) and extensive skin involvement (BSA >10%), showed significantly better persistence for UST (HR 0.61 [0.42, 0.90] and 0.41 [0.19, 0.89] respectively; unadjusted Kaplan-Meier graphs shown in Fig. 1c, d). MTX co-therapy and low BSA did not affect the PS-adjusted treatment effect. Other factors added to the PS-adjusted Cox model did not show significant effects.Conclusion:In this real-world PsA cohort undergoing bDMARD treatment, persistence was generally comparable for UST and TNFi, but some clinical situations led to better drug persistence with UST compared to TNFi – particularly monotherapy, more extensive skin involvement, and in 3rd-line treatment. Our data emphasise the importance of skin involvement for pts with PsA.References:[1]Gossec L, et al.Ann Rheum Dis. 2018;77(suppl 2):Abstract AB0928Acknowledgments:This study was funded by Janssen.Disclosure of Interests:Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Stefan Siebert Grant/research support from: BMS, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Celgene, Janssen, Novartis, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Kurt de Vlam Consultant of: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – consultant, Speakers bureau: Celgene Corporation, Eli Lilly, Novartis, Pfizer, UCB – speakers bureau and honoraria, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Beatriz Joven-Ibáñez Speakers bureau: Abbvie, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Wim Noel Employee of: Janssen Pharmaceuticals NV, Michael T Nurmohamed Grant/research support from: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Consultant of: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Speakers bureau: Abbvie, Bristol-Myers Squibb, Celltrion, GlaxoSmithKline, Jansen, Eli Lilly, Menarini, Merck Sharp & Dohme, Mundipharma, Pfizer, Roche, Sanofi, USB, Petros Sfikakis Grant/research support from: Grant/research support from Abvie, Novartis, MSD, Actelion, Amgen, Pfizer, Janssen Pharmaceutical, UCB, Elke Theander Employee of: Janssen-Cilag Sweden AB, Josef S. Smolen Grant/research support from: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi, Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Samsung, Sanofi

scholarly journals Comparative effectiveness of subcutaneous tocilizumab versus intravenous tocilizumab in a pan-European collaboration of registries

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000809 ◽  
Author(s):  
Kim Lauper ◽  
Denis Mongin ◽  
Florenzo Iannone ◽  
Eirik Klami Kristianslund ◽  
Tore K Kvien ◽  
...  
Keyword(s):  
Disease Activity ◽  
Comparative Effectiveness ◽  
Treatment Initiation ◽  
Activity Index ◽  
Disease Activity Index ◽  
Real Word ◽  
Cox Models ◽  
Low Disease Activity ◽  
Kaplan Meier ◽  
European Collaboration

ObjectiveTo compare the real-word effectiveness of subcutaneous tocilizumab (TCZ-SC) and intravenous tocilizumab (TCZ-IV) in rheumatoid arthritis (RA).MethodsPatients with RA with TCZ from eight European registries were included. Drug retention was compared using unadjusted Kaplan-Meier and Cox models adjusted for baseline patient, disease and treatment characteristics, using a strata term for year of treatment initiation and country of registry. The proportions of patients achieving Clinical Disease Activity Index (CDAI) remission and low disease activity (LDA) at 1 year were compared using samples matched on the same covariates and corrected for attrition using LUNDEX.Results3448 patients were retrieved, 2414 with TCZ-IV and 1034 with TCZ-SC. Crude median retention was 3.52 years (95% CI 3.22 to 3.85) for TCZ-IV and 2.12 years for TCZ-SC (95% CI 1.88 to 2.38). In a country-stratified and year of treatment initiation–stratified, covariate-adjusted analysis, hazards of discontinuation were similar between TCZ-SC and TCZ-IV treated patients (HR 0.93, 95% CI 0.80 to 1.09). The average adjusted CDAI change at 1 year was similar in both groups (−6.08). After matching, with 560 patients in each group, CDAI remission corrected for attrition at 1 year was also similar between TCZ-SC and TCZ-IV (10.4% in TCZ-IV vs 12.8% in TCZ-SC (difference: 2.4%, bootstrap 95% CI −2.1% to 7.6%)), but CDAI LDA was lower in TCZ-IV patients: 41.0% in TCZ-IV versus 49.1% in TCZ-SC (difference: 8.0 %; bootstrap 95% CI 2.4% to 12.4%).ConclusionWith similar retention and effectiveness, TCZ-SC is an adequate alternative to TCZ-IV for RA. When possible, considering the costs of the TCZ-IV route, TCZ-SC should be the preferred mode of administration.

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