Objective. To assess the longterm efficacy and safety of golimumab in patients with active rheuma... more Objective. To assess the longterm efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods. We randomized 444 RA patients with inadequate response to MTX (3:3:2:2) to placebo + MTX (Group 1), golimumab 100 mg + placebo (Group 2), golimumab 50 mg + MTX (Group 3), or golimumab 100 mg + MTX (Group 4). Subcutaneous golimumab/placebo was injected every 4 weeks. Patients could escape early (Group 1 added golimumab 50 mg, Group 2 added MTX, Group 3 increased golimumab to 100 mg, Group 4 continued 100 mg) based on Week 16 swollen and tender joint counts. From Week 24, Group 1 patients received golimumab 50 mg + MTX. After the Week 52 database lock, patients in the longterm extension received golimumab 50-100 mg ± MTX. Coprimary endpoints [Week 14 American College of Rheumatology (ACR)20, Week 24 Health Assessment Questionnaire Disability Index (HAQ-DI)] and Week 52 findings have been published; 2-year findings (observed data by randomized group, no imputation) are presented. Results. Of 444 randomized patients, 392 continued from Week 52 (Group 1: n = 116, Group 2: n = 116, Group 3: n = 84, Group 4: n = 76). Clinical improvement was maintained through Week 104; 75% and 72% of patients randomized to golimumab 50 mg + MTX and 100 mg + MTX achieved ACR20 response, respectively. The majority [88% (105/120)] of golimumab + MTX-treated patients with Week 24 HAQ-DI improvement ≥ 0.25 maintained improved physical function through Week 104. Group 1 patients with delayed golimumab treatment exhibited more Week 104 radiographic progression (mean change score = 1.15) than golimumab + MTX-randomized patients (0.52). Incidences of serious infections were 2.24, 4.77, 5.78/100 patient-years of followup for golimumab 50 mg + MTX, 100 mg + placebo, and 100 mg + MTX, respectively. Conclusion. Clinical improvement was maintained and no new safety signals were identified with 2 years of golimumab + MTX. Golimumab efficacy and safety, including serious infections, will continue to be monitored through 5 years (Clinical Trial No. NCT00264550).
background in seleCT-COMPaRe, a randomised double-blind study, upadacitinib 15 mg once daily was ... more background in seleCT-COMPaRe, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response. Methods Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (sJC) (weeks 14/18/22) or Clinical Disease activity index (CDai) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patientyears were summarised. Results Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDai ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. safety at week 48 was comparable to week 26. Conclusion Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout. Key messages What is already known about this subject? ► In patients with rheumatoid arthritis (RA) who do not respond sufficiently to biologic diseasemodifying antirheumatic drug (bDMARD) treatment with Janus kinase inhibitors (JAKi) is efficacious. ► Switching of therapies including switching from a JAKi to a bDMARD may be required to achieve treatment goals. ► In the SELECT-COMPARE study, through 6 months, upadacitinib demonstrated significant improvements in RA signs and symptoms versus placebo and adalimumab and inhibited radiographical progression versus placebo. What does this study add? ► Consistent with responses through week 26, between weeks 26 and 48 of the SELECT-COMPARE study, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab and radiographical progression remained lower for upadacitinib versus placebo. Safety at week 48 was comparable to findings through week 26. ► The SELECT-COMPARE study design incorporated blinded treatment switches within the first 6 months that allocated patients who were not sufficiently responding to randomised treatment to the alternative advanced therapy (ie, insufficient responders to upadacitinib were switched without washout to adalimumab and insufficient responders to adalimumab were switched without washout to upadacitinib). Both switch groups responded, but a higher proportion of patients rescued to upadacitinib from adalimumab achieved Clinical Disease Activity Index ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab.
positive patients. Furthermore, in these patients, failure to achieve remission is mostly related... more positive patients. Furthermore, in these patients, failure to achieve remission is mostly related to high PGA rather than to the persistence of joint inflammation. Altogether, these findings implicate that autoantibody-negative RA patients failing to achieve remission would require adjunctive tailored interventions rather than reinforcement of DMARD therapy.
Background Rheumatoid Arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of u... more Background Rheumatoid Arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of unknown etiology characterized by symmetric synovitis leading to cartilage damage1. Chronic and severe RA is associated with a 50% higher risk of death from cardiovascular disease (CVD) compared with healthy controls2. Moreover, Active RA is associated with an unfavorable lipid profile resulting in a higher atherogenic index3. Secukinumab, a fully human anti-IL-17A monoclonal antibody has shown to improve signs and symptoms of patients with active RA in this phase II trial4. Evaluation of the effect of secukinumab on lipids is potentially relevant as current guidelines recommend treatment if hypercholesterolemia is associated with elevated CV risk5. Objectives To report the effect of secukinumab on the lipid profile and atherogenic indexes in patients with active RA despite stable methotrexate (MTX) treatment. Methods Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. After Week (wk) 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at wk20 (except patients initially on 300mg who remained on the same dose). All placebo patients were switched to secukinumab 150mg. Patients were followed up to wk52. Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at wk16. Results Demographics, baseline characteristics and lipid parameters were normal and comparable across all treatment groups. There was no effect of secukinumab on the lipid profile (Total Cholesterol, HDLc, LDLc, TG, Apo A-I and Apo B) during the first 16 wks of treatment in all treatment groups when compared to placebo. Atherogenic indices (TC/HDLc and Apo B/Apo A-I ratio also remained unchanged during first 16 wks of therapy (Table 1). In patients who switched from placebo to secukinumab 150mg at wk20, TC/HDLc and Apo B/Apo A-I ratios remained unchanged throughout the duration of the study (wk0-52). The efficacy and safety of this study group has been reported previously and did not report any CV event3. Conclusions Treatment with secukinumab was not associated with changes in the lipid profile or the atherogenic risk in patients with RA. References Voulgari PV. Expert Opin Emerg Drugs. 2009; 13:175-96. Avina-Zubieta JA. Arthritis Rheum. 2008; 59: 1690-7. Myasoedova E et al. Ann Rheum Dis. 2010; 69:1310-4. Mark C. Genovese. Arthritis Rheum. 2011;63(10[suppl]):S149-S150. Peters MJL et al. Int J Clin Prac 2010; 64:1440-3. Disclosure of Interest P. Durez: None Declared, M. Genovese Grant/Research support from: Novartis, H. Kellner: None Declared, C. Codding: None Declared, G. Ligozio Employee of: Novartis Pharmaceuticals Corporation, H. Richards Employee of: Novartis Pharma AG, C. Escrig Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, S. Mpofu Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG
This is a repository copy of MRI of the joint and evaluation of the granulocyte-macrophage colony... more This is a repository copy of MRI of the joint and evaluation of the granulocyte-macrophage colony-stimulating factor-CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study.
Background A key goal in rheumatoid arthritis (RA) therapy is to achieve remission or at least ve... more Background A key goal in rheumatoid arthritis (RA) therapy is to achieve remission or at least very low disease activity1. Secukinumab, a fully human anti-IL-17A monoclonal antibody has been shown to improve signs and symptoms of patients with active RA in this phase II trial2. Objectives To report the effect of secukinumab treatment on disease activity in patients with active RA despite stable methotrexate (MTX) treatment. Methods Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. After Week (wk) 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at wk20 (except patients initially on 300mg who remained on the same dose). At wk20, all placebo patients were switched to secukinumab 150mg. All patients were followed up to wk52. Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at wk16. Secondary efficacy endpoints are presented here using ACR50, Health Assessment Questionnaire (HAQ-DI) and EULAR remission rate (DAS28-CRP≤2.6). Results Demographics and baseline characteristics were comparable across treatment groups. The primary endpoint ACR 20 at wk16 was not achieved. ACR50 responses at wk24 and wk52 were highest in patients who remained on secukinumab 150mg for the entire study (ACR50: wk24=50%; wk52=55%). HAQ scores improved over time in responders on secukinumab 150mg (wk24=-0.6; wk52=-0.8). At wk16, the proportion of patients achieving EULAR remission response was 11.3% for 25mg, 6.1% for 75mg, 11.6% for 150mg, 14.6% for 300mg and 6% for placebo. The percentage of patients achieving EULAR remission increased overtime and were highest in patients on secukinumab 150mg (wk24=30%, wk52=40%). Additionally, patients who responded on placebo but switched to secukinumab 150mg at wk20 achieved similar EULAR remission rates that patients receiving secukinumab 150mg for the entire study (wk24=29.4%; wk52=38.9%). Non-responders did not gain much additional efficacy benefit after dose escalation as assessed by ACR50, HAQ and EULAR remission criteria. The safety data for this cohort has been previously described2. Overall rates of adverse events (AEs) at wk52 was comparable to data up to wk20 and most AEs were mild to moderate in severity and did not lead to study discontinuation. Conclusions The primary efficacy endpoint was not achieved in this study. Analysis of secondary endpoints suggest that a substantial proportion of patients achieved a consistent ACR50, HAQ-DI and EULAR remission rates improvements through Wk52 in patients with active RA despite stable MTX treatmentwho either remained on or escalated to secukinumab 150mg were observed. These results provide potential evidence for the role of secukinumab in the treatment of RA and support further exploration of secukinumab in RA. References Sesin CA, Bingham CO 3rd. Semin Arthritis Rheum. 2005;35(3):185–96. Genovese M., et al. Arthritis Rheum. 2011;63(10[suppl]):S149–S150. Disclosure of Interest M. Genovese Grant/Research support from: Novartis, H. Kellner: None Declared, P. Durez: None Declared, C. Codding: None Declared, G. Ligozio Employee of: Novartis Pharmaceuticals Corporation, H. Richards Employee of: Novartis Pharma AG, C. Escrig Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, S. Mpofu Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG
Background: With the availability of multiple Jak inhibitors (JAKi) for treatment, patients with ... more Background: With the availability of multiple Jak inhibitors (JAKi) for treatment, patients with RA who have had inadequate response to conventional therapies, including biologics, can now achieve favorable outcomes such as remission and low disease activity. However, it is also true that no single JAKi therapy is effective for all RA. Some RA treatment guidelines recommend a switch strategy from current JAKi to other JAKi or biologics in patients with inadequate response to JAKi therapy [1]. There is insufficient evidence to support the efficacy of switching to another JAKi in patients with inadequate JAKi response (JAKi-IR). Objectives: The aim of this study is to clarify the effectiveness of the strategy of controlling disease activity by switching to other JAKi in RA cases with JAKi-IR and to analyze the effect on serum cytokines related to the pathogenesis of RA. Methods: RA patients who switched to other JAKi during treatment with JAKi between September 2017 and January 2022 were included in this retrospective
Adherence by CQR was evaluated as taking compliance >80% and CQR total score. Influencing factors... more Adherence by CQR was evaluated as taking compliance >80% and CQR total score. Influencing factors were identified by a multiple regression model relating individual MTX adherence rate to predictors duration of RA, age, gender, current MTX dose, MTX route of application, duration of MTX therapy and number of concomitant DMARDs. Results: A total of 519 patients in 21 outpatient centers were included (25.0% males, 75.0% females, age 58.3±12.6 [Mean ± SD] years, RA since 11.3±8.7 years, MTX therapy since 6.9±5.0 years) with 477 returning analyzable questionnaires. 90.6 (87.6-93.0; 95% CI) % of patients reported >80% adherence to MTX therapy, 73.0 (68.7-76.9) % reported full adherence (total N =477). Mean individual adherence rate was 93.9±16.7%. Main reason for non-adherence was unintentional omission of one or more doses (16.7% of patients). Results for other self-administered DMARDs were similar, >80% adherence ranged between 82.1 (63.1-93.9) % for Certolizumab and 100.0 (78.2-100.0) % for Abatacept s.c. Adherence calculated from the CQR differed considerably (CQR taking compliance >80%: 36.3% [32.0-40.7] % of patients). There was nearly no agreement between CQR compliance >80% and SSQ >80% adherence to MTX (Cohen's kappa =0.007; total N =458). But there was some agreement between CQR total score (75.4±9.7; total N =499) and SSQ individual adherence rate (Spearman rank correlation =0.223; total N =458). Only influencing factors were current MTX dose (p =0.006; patients with higher doses more adherent), and age (p =0.017; older patients more adherent). Conclusions: Patient-reported adherence to MTX as well as other DMARD therapy is high in Germany according to SSQ. Considerable difference exists, however, between high adherence directly reported by patients (SSQ) and low adherence assessed by CQR. Factors influencing adherence to MTX therapy include current MTX dose and patients' age. Unintentional omission of doses was the main reason for non-adherence. References:
ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumato... more ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (7...
Background:In the SELECT-COMPARE study in rheumatoid arthritis (RA) patients with inadequate resp... more 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...
OBJECTIVE This study aimed to evaluate the long-term safety and efficacy of olokizumab (OKZ), an ... more OBJECTIVE This study aimed to evaluate the long-term safety and efficacy of olokizumab (OKZ), an anti-interleukin (IL)-6 monoclonal antibody, in patients with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor-alpha inhibitors. METHODS Eligible patients completed study RA0056, which tested several doses of OKZ, placebo (PBO), and tocilizumab (TCZ) plus methotrexate (MTX) in Western countries, and RA0083 included several doses of OKZ and PBO plus MTX in Asian countries. Both studies were followed by open-label extension (OLE) studies with OKZ 120 mg every 2 weeks, RA0057 and RA0089, respectively. Safety assessments were reported up to 124 weeks in RA0057 and 92 weeks in RA0089. Efficacy assessments were reported up to week 60 in RA0057 and week 52 in RA0089. No formal statistical hypothesis testing was performed, and missing data were not imputed. RESULTS A total of 190 patients in RA0057 and 103 patients in RA0089 received OKZ with median treatment duration of 14.1 and 10.1 months, respectively. Serious adverse events (SAEs) were reported in 44 patients (23.2%, 32.7 events per 100 patient-years [PY]) in RA0057 and in 13 patients (12.6%, 23.6 events per 100 PY) in RA0089. Among treatment-emergent adverse events (TEAEs), including SAEs, infections were the most common events. TEAEs leading to withdrawal were reported in 33 (17.4%) patients in RA0057 and in 7 (6.8%) patients in RA0089. Disease activity score 28-joint count on the basis of C-reactive protein level, clinical disease activity index, and simplified disease activity index, as well as the American College of Rheumatology 20%, 50%, and 70% response rates were maintained during the OLE studies, including in those who switched from PBO or TCZ. Improvements in patient-reported outcomes were maintained in OLEs as well. CONCLUSION In the 2 long-term studies, OKZ treatment demonstrated a safety profile expected for IL-6 blocking agents without new safety signals and led to sustained improvements in RA symptoms, physical function, and quality of life.
Background:For patients with rheumatoid arthritis (RA), long-term prevention of structural joint ... more Background:For patients with rheumatoid arthritis (RA), long-term prevention of structural joint damage is a key treatment goal.1In the SELECT-EARLY and SELECT-COMPARE trials, upadacitinib (UPA), an oral JAK inhibitor, inhibited the progression of structural joint damage at 6 months and 1 year when used either as monotherapy or in combination with methotrexate (MTX) in patients (pts) with active RA.2Objectives:To describe the radiographic progression up to 2 years (96 wks) among pts with RA receiving UPA either as monotherapy or in combination with MTX.Methods:Both the SELECT-EARLY and SELECT-COMPARE phase 3, randomized controlled trials enrolled pts at high risk for progressive structural damage with baseline (BL) erosive joint damage and/or seropositivity.3,4In SELECT-EARLY, MTX-naïve pts (N=945) were randomized to UPA 15 mg or 30 mg once daily (QD) or MTX monotherapy. In SELECT-COMPARE, pts with an inadequate response to MTX (N=1629) were randomized to UPA 15 mg, placebo (PBO), o...
Background Long-term prevention of structural joint damage is a key treatment goal in the managem... more Background Long-term prevention of structural joint damage is a key treatment goal in the management of RA. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)-naïve RA patients and in combination with MTX in patients with inadequate response (IR) to MTX. Objectives: To evaluate the progression of structural joint damage (radiographic) through Week 48 in patients with moderately to severely active RA treated with UPA monotherapy or in combination with MTX. Methods Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs). MTX-naïve patients were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT-EARLY, N = 945], while MTX-IR patients were randomized to UPA 15mg QD or adalimumab (ADA) 40 mg eow or placebo (PBO), with continuous background MTX [SELECT-COMPARE, N = 1629]. Both RCTs specifically enrolled patients at high risk for progression of joint dam...
Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved... more Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults in over 50 countries. Objective: To evaluate the long-term safety of BARI in patients with RA with a specific focus on malignancies, major adverse cardiovascular events (MACE), serious infections and herpes zoster (HZ) events. Methods Data from nine completed studies (5 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 long term extension (LTE) study were pooled for this analysis (data cut-off date: 13-Feb-2018). The all BARI data set included all patients exposed to any BARI dose. Results A total of 3,770 patients with RA were treated with BARI (10,127 patient years [PY]) with a maximum exposure of 7 years. Of these, 2,938 (78%) and 1,754 (47%) were on concomitant methotrexate or corticosteroids (CS; mean dose 6.2 mg/day), respectively. The incidence rates (IR) of malignancy (excluding non-melanoma skin cancer) ...
ObjectiveTo evaluate the efficacy, including capacity for inhibition of radiographic progression,... more ObjectiveTo evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1‐selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX).MethodsIn total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) of <2.6 in the upadacitinib group compared to the placebo group at week 12; inhibition of radiographic progression was evaluated at week 26. The study was also designed and powered to test for the noninferiority and superiority of upadacitinib compared ...
Arthritis & rheumatology (Hoboken, N.J.), Jan 31, 2018
This study investigated the safety and efficacy of ABT-122, a TNF- and IL-17A-targeted dual varia... more This study investigated the safety and efficacy of ABT-122, a TNF- and IL-17A-targeted dual variable domain immunoglobulin, in patients with active psoriatic arthritis (PsA) with an inadequate response to methotrexate. Patients (N=240) were randomized to receive ABT-122 (120 or 240 mg every week), adalimumab (40 mg every other week), or placebo in a 12-week, double-blind, parallel-group study (NCT02349451). The primary efficacy endpoint was ≥20% improvement in American College of Rheumatology criteria (ACR20 response) at week 12. Secondary and exploratory 12-week endpoints included ACR50, ACR70, and Psoriasis Area and Severity Index (PASI75 and PASI90 skin scores) in patients with ≥3% body surface affected. For both ABT-122 dose groups, ACR20 responses at week 12 (64.8% to 75.3%) were superior to placebo (25.0%; P<0.001) but not adalimumab (68.1%). ACR50 and ACR70 responses were also superior for both ABT-122 dose groups (36.6% to 53.4% and 22.5% to 31.5%, respectively) versus pl...
Toute reproduction, utilisation commerciale ou éducative doit faire référence à la publication d'... more Toute reproduction, utilisation commerciale ou éducative doit faire référence à la publication d'origine (ARD/BMJ).
Objective. To assess the longterm efficacy and safety of golimumab in patients with active rheuma... more Objective. To assess the longterm efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. Methods. We randomized 444 RA patients with inadequate response to MTX (3:3:2:2) to placebo + MTX (Group 1), golimumab 100 mg + placebo (Group 2), golimumab 50 mg + MTX (Group 3), or golimumab 100 mg + MTX (Group 4). Subcutaneous golimumab/placebo was injected every 4 weeks. Patients could escape early (Group 1 added golimumab 50 mg, Group 2 added MTX, Group 3 increased golimumab to 100 mg, Group 4 continued 100 mg) based on Week 16 swollen and tender joint counts. From Week 24, Group 1 patients received golimumab 50 mg + MTX. After the Week 52 database lock, patients in the longterm extension received golimumab 50-100 mg ± MTX. Coprimary endpoints [Week 14 American College of Rheumatology (ACR)20, Week 24 Health Assessment Questionnaire Disability Index (HAQ-DI)] and Week 52 findings have been published; 2-year findings (observed data by randomized group, no imputation) are presented. Results. Of 444 randomized patients, 392 continued from Week 52 (Group 1: n = 116, Group 2: n = 116, Group 3: n = 84, Group 4: n = 76). Clinical improvement was maintained through Week 104; 75% and 72% of patients randomized to golimumab 50 mg + MTX and 100 mg + MTX achieved ACR20 response, respectively. The majority [88% (105/120)] of golimumab + MTX-treated patients with Week 24 HAQ-DI improvement ≥ 0.25 maintained improved physical function through Week 104. Group 1 patients with delayed golimumab treatment exhibited more Week 104 radiographic progression (mean change score = 1.15) than golimumab + MTX-randomized patients (0.52). Incidences of serious infections were 2.24, 4.77, 5.78/100 patient-years of followup for golimumab 50 mg + MTX, 100 mg + placebo, and 100 mg + MTX, respectively. Conclusion. Clinical improvement was maintained and no new safety signals were identified with 2 years of golimumab + MTX. Golimumab efficacy and safety, including serious infections, will continue to be monitored through 5 years (Clinical Trial No. NCT00264550).
background in seleCT-COMPaRe, a randomised double-blind study, upadacitinib 15 mg once daily was ... more background in seleCT-COMPaRe, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response. Methods Patients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (sJC) (weeks 14/18/22) or Clinical Disease activity index (CDai) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patientyears were summarised. Results Consistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDai ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. safety at week 48 was comparable to week 26. Conclusion Upadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout. Key messages What is already known about this subject? ► In patients with rheumatoid arthritis (RA) who do not respond sufficiently to biologic diseasemodifying antirheumatic drug (bDMARD) treatment with Janus kinase inhibitors (JAKi) is efficacious. ► Switching of therapies including switching from a JAKi to a bDMARD may be required to achieve treatment goals. ► In the SELECT-COMPARE study, through 6 months, upadacitinib demonstrated significant improvements in RA signs and symptoms versus placebo and adalimumab and inhibited radiographical progression versus placebo. What does this study add? ► Consistent with responses through week 26, between weeks 26 and 48 of the SELECT-COMPARE study, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab and radiographical progression remained lower for upadacitinib versus placebo. Safety at week 48 was comparable to findings through week 26. ► The SELECT-COMPARE study design incorporated blinded treatment switches within the first 6 months that allocated patients who were not sufficiently responding to randomised treatment to the alternative advanced therapy (ie, insufficient responders to upadacitinib were switched without washout to adalimumab and insufficient responders to adalimumab were switched without washout to upadacitinib). Both switch groups responded, but a higher proportion of patients rescued to upadacitinib from adalimumab achieved Clinical Disease Activity Index ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab.
positive patients. Furthermore, in these patients, failure to achieve remission is mostly related... more positive patients. Furthermore, in these patients, failure to achieve remission is mostly related to high PGA rather than to the persistence of joint inflammation. Altogether, these findings implicate that autoantibody-negative RA patients failing to achieve remission would require adjunctive tailored interventions rather than reinforcement of DMARD therapy.
Background Rheumatoid Arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of u... more Background Rheumatoid Arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of unknown etiology characterized by symmetric synovitis leading to cartilage damage1. Chronic and severe RA is associated with a 50% higher risk of death from cardiovascular disease (CVD) compared with healthy controls2. Moreover, Active RA is associated with an unfavorable lipid profile resulting in a higher atherogenic index3. Secukinumab, a fully human anti-IL-17A monoclonal antibody has shown to improve signs and symptoms of patients with active RA in this phase II trial4. Evaluation of the effect of secukinumab on lipids is potentially relevant as current guidelines recommend treatment if hypercholesterolemia is associated with elevated CV risk5. Objectives To report the effect of secukinumab on the lipid profile and atherogenic indexes in patients with active RA despite stable methotrexate (MTX) treatment. Methods Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. After Week (wk) 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at wk20 (except patients initially on 300mg who remained on the same dose). All placebo patients were switched to secukinumab 150mg. Patients were followed up to wk52. Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at wk16. Results Demographics, baseline characteristics and lipid parameters were normal and comparable across all treatment groups. There was no effect of secukinumab on the lipid profile (Total Cholesterol, HDLc, LDLc, TG, Apo A-I and Apo B) during the first 16 wks of treatment in all treatment groups when compared to placebo. Atherogenic indices (TC/HDLc and Apo B/Apo A-I ratio also remained unchanged during first 16 wks of therapy (Table 1). In patients who switched from placebo to secukinumab 150mg at wk20, TC/HDLc and Apo B/Apo A-I ratios remained unchanged throughout the duration of the study (wk0-52). The efficacy and safety of this study group has been reported previously and did not report any CV event3. Conclusions Treatment with secukinumab was not associated with changes in the lipid profile or the atherogenic risk in patients with RA. References Voulgari PV. Expert Opin Emerg Drugs. 2009; 13:175-96. Avina-Zubieta JA. Arthritis Rheum. 2008; 59: 1690-7. Myasoedova E et al. Ann Rheum Dis. 2010; 69:1310-4. Mark C. Genovese. Arthritis Rheum. 2011;63(10[suppl]):S149-S150. Peters MJL et al. Int J Clin Prac 2010; 64:1440-3. Disclosure of Interest P. Durez: None Declared, M. Genovese Grant/Research support from: Novartis, H. Kellner: None Declared, C. Codding: None Declared, G. Ligozio Employee of: Novartis Pharmaceuticals Corporation, H. Richards Employee of: Novartis Pharma AG, C. Escrig Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, S. Mpofu Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG
This is a repository copy of MRI of the joint and evaluation of the granulocyte-macrophage colony... more This is a repository copy of MRI of the joint and evaluation of the granulocyte-macrophage colony-stimulating factor-CCL17 axis in patients with rheumatoid arthritis receiving otilimab: a phase 2a randomised mechanistic study.
Background A key goal in rheumatoid arthritis (RA) therapy is to achieve remission or at least ve... more Background A key goal in rheumatoid arthritis (RA) therapy is to achieve remission or at least very low disease activity1. Secukinumab, a fully human anti-IL-17A monoclonal antibody has been shown to improve signs and symptoms of patients with active RA in this phase II trial2. Objectives To report the effect of secukinumab treatment on disease activity in patients with active RA despite stable methotrexate (MTX) treatment. Methods Adult RA patients (n=237) on MTX were randomized equally to receive monthly s.c injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. After Week (wk) 16, responders on secukinumab remained on the same dose whereas doses were escalated in non-responders at wk20 (except patients initially on 300mg who remained on the same dose). At wk20, all placebo patients were switched to secukinumab 150mg. All patients were followed up to wk52. Primary endpoint was the proportion of patients achieving American College of Rheumatology (ACR) 20 at wk16. Secondary efficacy endpoints are presented here using ACR50, Health Assessment Questionnaire (HAQ-DI) and EULAR remission rate (DAS28-CRP≤2.6). Results Demographics and baseline characteristics were comparable across treatment groups. The primary endpoint ACR 20 at wk16 was not achieved. ACR50 responses at wk24 and wk52 were highest in patients who remained on secukinumab 150mg for the entire study (ACR50: wk24=50%; wk52=55%). HAQ scores improved over time in responders on secukinumab 150mg (wk24=-0.6; wk52=-0.8). At wk16, the proportion of patients achieving EULAR remission response was 11.3% for 25mg, 6.1% for 75mg, 11.6% for 150mg, 14.6% for 300mg and 6% for placebo. The percentage of patients achieving EULAR remission increased overtime and were highest in patients on secukinumab 150mg (wk24=30%, wk52=40%). Additionally, patients who responded on placebo but switched to secukinumab 150mg at wk20 achieved similar EULAR remission rates that patients receiving secukinumab 150mg for the entire study (wk24=29.4%; wk52=38.9%). Non-responders did not gain much additional efficacy benefit after dose escalation as assessed by ACR50, HAQ and EULAR remission criteria. The safety data for this cohort has been previously described2. Overall rates of adverse events (AEs) at wk52 was comparable to data up to wk20 and most AEs were mild to moderate in severity and did not lead to study discontinuation. Conclusions The primary efficacy endpoint was not achieved in this study. Analysis of secondary endpoints suggest that a substantial proportion of patients achieved a consistent ACR50, HAQ-DI and EULAR remission rates improvements through Wk52 in patients with active RA despite stable MTX treatmentwho either remained on or escalated to secukinumab 150mg were observed. These results provide potential evidence for the role of secukinumab in the treatment of RA and support further exploration of secukinumab in RA. References Sesin CA, Bingham CO 3rd. Semin Arthritis Rheum. 2005;35(3):185–96. Genovese M., et al. Arthritis Rheum. 2011;63(10[suppl]):S149–S150. Disclosure of Interest M. Genovese Grant/Research support from: Novartis, H. Kellner: None Declared, P. Durez: None Declared, C. Codding: None Declared, G. Ligozio Employee of: Novartis Pharmaceuticals Corporation, H. Richards Employee of: Novartis Pharma AG, C. Escrig Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG, S. Mpofu Shareholder of: Novartis Pharma AG, Employee of: Novartis Pharma AG
Background: With the availability of multiple Jak inhibitors (JAKi) for treatment, patients with ... more Background: With the availability of multiple Jak inhibitors (JAKi) for treatment, patients with RA who have had inadequate response to conventional therapies, including biologics, can now achieve favorable outcomes such as remission and low disease activity. However, it is also true that no single JAKi therapy is effective for all RA. Some RA treatment guidelines recommend a switch strategy from current JAKi to other JAKi or biologics in patients with inadequate response to JAKi therapy [1]. There is insufficient evidence to support the efficacy of switching to another JAKi in patients with inadequate JAKi response (JAKi-IR). Objectives: The aim of this study is to clarify the effectiveness of the strategy of controlling disease activity by switching to other JAKi in RA cases with JAKi-IR and to analyze the effect on serum cytokines related to the pathogenesis of RA. Methods: RA patients who switched to other JAKi during treatment with JAKi between September 2017 and January 2022 were included in this retrospective
Adherence by CQR was evaluated as taking compliance >80% and CQR total score. Influencing factors... more Adherence by CQR was evaluated as taking compliance >80% and CQR total score. Influencing factors were identified by a multiple regression model relating individual MTX adherence rate to predictors duration of RA, age, gender, current MTX dose, MTX route of application, duration of MTX therapy and number of concomitant DMARDs. Results: A total of 519 patients in 21 outpatient centers were included (25.0% males, 75.0% females, age 58.3±12.6 [Mean ± SD] years, RA since 11.3±8.7 years, MTX therapy since 6.9±5.0 years) with 477 returning analyzable questionnaires. 90.6 (87.6-93.0; 95% CI) % of patients reported >80% adherence to MTX therapy, 73.0 (68.7-76.9) % reported full adherence (total N =477). Mean individual adherence rate was 93.9±16.7%. Main reason for non-adherence was unintentional omission of one or more doses (16.7% of patients). Results for other self-administered DMARDs were similar, >80% adherence ranged between 82.1 (63.1-93.9) % for Certolizumab and 100.0 (78.2-100.0) % for Abatacept s.c. Adherence calculated from the CQR differed considerably (CQR taking compliance >80%: 36.3% [32.0-40.7] % of patients). There was nearly no agreement between CQR compliance >80% and SSQ >80% adherence to MTX (Cohen's kappa =0.007; total N =458). But there was some agreement between CQR total score (75.4±9.7; total N =499) and SSQ individual adherence rate (Spearman rank correlation =0.223; total N =458). Only influencing factors were current MTX dose (p =0.006; patients with higher doses more adherent), and age (p =0.017; older patients more adherent). Conclusions: Patient-reported adherence to MTX as well as other DMARD therapy is high in Germany according to SSQ. Considerable difference exists, however, between high adherence directly reported by patients (SSQ) and low adherence assessed by CQR. Factors influencing adherence to MTX therapy include current MTX dose and patients' age. Unintentional omission of doses was the main reason for non-adherence. References:
ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumato... more ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (7...
Background:In the SELECT-COMPARE study in rheumatoid arthritis (RA) patients with inadequate resp... more 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...
OBJECTIVE This study aimed to evaluate the long-term safety and efficacy of olokizumab (OKZ), an ... more OBJECTIVE This study aimed to evaluate the long-term safety and efficacy of olokizumab (OKZ), an anti-interleukin (IL)-6 monoclonal antibody, in patients with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor-alpha inhibitors. METHODS Eligible patients completed study RA0056, which tested several doses of OKZ, placebo (PBO), and tocilizumab (TCZ) plus methotrexate (MTX) in Western countries, and RA0083 included several doses of OKZ and PBO plus MTX in Asian countries. Both studies were followed by open-label extension (OLE) studies with OKZ 120 mg every 2 weeks, RA0057 and RA0089, respectively. Safety assessments were reported up to 124 weeks in RA0057 and 92 weeks in RA0089. Efficacy assessments were reported up to week 60 in RA0057 and week 52 in RA0089. No formal statistical hypothesis testing was performed, and missing data were not imputed. RESULTS A total of 190 patients in RA0057 and 103 patients in RA0089 received OKZ with median treatment duration of 14.1 and 10.1 months, respectively. Serious adverse events (SAEs) were reported in 44 patients (23.2%, 32.7 events per 100 patient-years [PY]) in RA0057 and in 13 patients (12.6%, 23.6 events per 100 PY) in RA0089. Among treatment-emergent adverse events (TEAEs), including SAEs, infections were the most common events. TEAEs leading to withdrawal were reported in 33 (17.4%) patients in RA0057 and in 7 (6.8%) patients in RA0089. Disease activity score 28-joint count on the basis of C-reactive protein level, clinical disease activity index, and simplified disease activity index, as well as the American College of Rheumatology 20%, 50%, and 70% response rates were maintained during the OLE studies, including in those who switched from PBO or TCZ. Improvements in patient-reported outcomes were maintained in OLEs as well. CONCLUSION In the 2 long-term studies, OKZ treatment demonstrated a safety profile expected for IL-6 blocking agents without new safety signals and led to sustained improvements in RA symptoms, physical function, and quality of life.
Background:For patients with rheumatoid arthritis (RA), long-term prevention of structural joint ... more Background:For patients with rheumatoid arthritis (RA), long-term prevention of structural joint damage is a key treatment goal.1In the SELECT-EARLY and SELECT-COMPARE trials, upadacitinib (UPA), an oral JAK inhibitor, inhibited the progression of structural joint damage at 6 months and 1 year when used either as monotherapy or in combination with methotrexate (MTX) in patients (pts) with active RA.2Objectives:To describe the radiographic progression up to 2 years (96 wks) among pts with RA receiving UPA either as monotherapy or in combination with MTX.Methods:Both the SELECT-EARLY and SELECT-COMPARE phase 3, randomized controlled trials enrolled pts at high risk for progressive structural damage with baseline (BL) erosive joint damage and/or seropositivity.3,4In SELECT-EARLY, MTX-naïve pts (N=945) were randomized to UPA 15 mg or 30 mg once daily (QD) or MTX monotherapy. In SELECT-COMPARE, pts with an inadequate response to MTX (N=1629) were randomized to UPA 15 mg, placebo (PBO), o...
Background Long-term prevention of structural joint damage is a key treatment goal in the managem... more Background Long-term prevention of structural joint damage is a key treatment goal in the management of RA. Upadacitinib (UPA), a JAK1-selective inhibitor, inhibited the progression of structural joint damage at 6 months as monotherapy in methotrexate (MTX)-naïve RA patients and in combination with MTX in patients with inadequate response (IR) to MTX. Objectives: To evaluate the progression of structural joint damage (radiographic) through Week 48 in patients with moderately to severely active RA treated with UPA monotherapy or in combination with MTX. Methods Radiographic progression was assessed in 2 phase 3 randomized controlled trials (RCTs). MTX-naïve patients were randomized to UPA 15 or 30mg QD or MTX monotherapy [SELECT-EARLY, N = 945], while MTX-IR patients were randomized to UPA 15mg QD or adalimumab (ADA) 40 mg eow or placebo (PBO), with continuous background MTX [SELECT-COMPARE, N = 1629]. Both RCTs specifically enrolled patients at high risk for progression of joint dam...
Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved... more Background Baricitinib (BARI) is a selective inhibitor of janus kinase (JAK) 1 and JAK2, approved for the treatment of moderately to severely active rheumatoid arthritis (RA) in adults in over 50 countries. Objective: To evaluate the long-term safety of BARI in patients with RA with a specific focus on malignancies, major adverse cardiovascular events (MACE), serious infections and herpes zoster (HZ) events. Methods Data from nine completed studies (5 Phase 3, 3 Phase 2, 1 Phase 1b) and 1 long term extension (LTE) study were pooled for this analysis (data cut-off date: 13-Feb-2018). The all BARI data set included all patients exposed to any BARI dose. Results A total of 3,770 patients with RA were treated with BARI (10,127 patient years [PY]) with a maximum exposure of 7 years. Of these, 2,938 (78%) and 1,754 (47%) were on concomitant methotrexate or corticosteroids (CS; mean dose 6.2 mg/day), respectively. The incidence rates (IR) of malignancy (excluding non-melanoma skin cancer) ...
ObjectiveTo evaluate the efficacy, including capacity for inhibition of radiographic progression,... more ObjectiveTo evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1‐selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX).MethodsIn total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) of <2.6 in the upadacitinib group compared to the placebo group at week 12; inhibition of radiographic progression was evaluated at week 26. The study was also designed and powered to test for the noninferiority and superiority of upadacitinib compared ...
Arthritis & rheumatology (Hoboken, N.J.), Jan 31, 2018
This study investigated the safety and efficacy of ABT-122, a TNF- and IL-17A-targeted dual varia... more This study investigated the safety and efficacy of ABT-122, a TNF- and IL-17A-targeted dual variable domain immunoglobulin, in patients with active psoriatic arthritis (PsA) with an inadequate response to methotrexate. Patients (N=240) were randomized to receive ABT-122 (120 or 240 mg every week), adalimumab (40 mg every other week), or placebo in a 12-week, double-blind, parallel-group study (NCT02349451). The primary efficacy endpoint was ≥20% improvement in American College of Rheumatology criteria (ACR20 response) at week 12. Secondary and exploratory 12-week endpoints included ACR50, ACR70, and Psoriasis Area and Severity Index (PASI75 and PASI90 skin scores) in patients with ≥3% body surface affected. For both ABT-122 dose groups, ACR20 responses at week 12 (64.8% to 75.3%) were superior to placebo (25.0%; P<0.001) but not adalimumab (68.1%). ACR50 and ACR70 responses were also superior for both ABT-122 dose groups (36.6% to 53.4% and 22.5% to 31.5%, respectively) versus pl...
Toute reproduction, utilisation commerciale ou éducative doit faire référence à la publication d'... more Toute reproduction, utilisation commerciale ou éducative doit faire référence à la publication d'origine (ARD/BMJ).
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