scholarly journals Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 2 trial

2021 ◽  
pp. annrheumdis-2021-221048
Author(s):  
Andrew Östör ◽  
Filip Van den Bosch ◽  
Kim Papp ◽  
Cecilia Asnal ◽  
Ricardo Blanco ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Primary Endpoint ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Patient Reported ◽  
Secondary Endpoints

ObjectivesRisankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here.MethodsAdults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes.ResultsA total of 444 patients (median age 53 years, range 23–84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, p<0.001) and all secondary endpoints (p<0.05) compared with placebo. Serious adverse events were reported for 4.0% and 5.5% of risankizumab-treated and placebo-treated patients, respectively; serious infections were reported for 0.9% and 2.3%, respectively.ConclusionTreatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR.Trial registration numberNCT03671148.

scholarly journals Upadacitinib in patients with psoriatic arthritis and an inadequate response to non-biological therapy: 56-week data from the phase 3 SELECT-PsA 1 study

RMD Open ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. e001838
Author(s):  
Iain B McInnes ◽  
Koji Kato ◽  
Marina Magrey ◽  
Joseph F Merola ◽  
Mitsumasa Kishimoto ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Severity Index ◽  
Inadequate Response ◽  
Phase 3 ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Acr Criteria ◽  
Minimal Disease

BackgroundIn SELECT-PsA 1, a randomised double-blind phase 3 study, upadacitinib 15 mg and 30 mg were superior to placebo and non-inferior to adalimumab in ≥20% improvement in American College of Rheumatology (ACR) criteria at 12 weeks in patients with psoriatic arthritis (PsA). Here, we report 56-week efficacy and safety in patients from SELECT-PsA 1.MethodsPatients received upadacitinib 15 mg or 30 mg once daily, adalimumab 40 mg every other week for 56 weeks or placebo through week 24 switched thereafter to upadacitinib 15 mg or 30 mg until week 56. Efficacy endpoints included the proportion of patients achieving ≥20%/50%/70% improvement in ACR criteria (ACR20/50/70), ≥75%/90%/100% improvement in Psoriasis Area and Severity Index (PASI75/90/100), minimal disease activity (MDA) and change from baseline in modified total Sharp/van der Heijde Score. Treatment-emergent adverse events per 100 patient years (PY) were summarised.ResultsConsistent with results through week 24, ACR20/50/70, PASI75/90/100 and MDA responses were maintained with upadacitinib through week 56 and were generally numerically higher than with adalimumab; inhibition of radiographic progression was also maintained. Patients who switched from placebo to upadacitinib exhibited comparable improvements at week 56 as patients originally randomised to upadacitinib. The rates of serious adverse events were 9.1 events/100 PY with upadacitinib 15 mg and 12.3 events/100 PY with upadacitinib 30 mg. Two deaths were reported in each of the upadacitinib groups.ConclusionEfficacy across various domains of PsA were maintained with upadacitinib 15 mg and 30 mg through week 56 with no new safety signals observed.

scholarly journals Efficacy and safety of netakimab in patients with psoriatic arthritis: results of the phase III PATERA clinical study

2020 ◽  
Vol 58 (5) ◽  
pp. 480-488
Author(s):  
T. V. Korotaeva ◽  
V. I. Mazurov ◽  
A. M. Lila ◽  
I. Z. Gaydukova ◽  
A. L. Bakulev ◽  
...  
Keyword(s):  
Placebo Group ◽  
Psoriatic Arthritis ◽  
Safety Profile ◽  
Phase Iii ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
Blinded Manner

Netakimab (NTK) is a humanized anti-interleukin-17А (IL-17A) monoclonal antibody approved for the treatment of psoriatic arthritis, ankylosing spondylitis, moderate to severe psoriasis. Here, we present the results of the 24-weeks double blind period of the PATERA study.Objective. The objective of the study was to evaluate the efficacy and safety of NTK compared to placebo in patients with psoriatic arthritis (PsA).Patients and methods. 194 patients with active PsA with an inadequate response to previous therapy with nonsteroidal anti-inflammatory drugs, conventional or biologic disease-modifying antirheumatic drugs, were randomized in a 1:1 ratio to receive subcutaneous 120 mg NTK or placebo at weeks 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. At week 16 ACR20 (20% improvement in the American College of Rheumatology response criteria) non-responders in placebo group were reassigned to NTK in a blinded manner. The primary endpoint was the proportion of patients achieved ACR20 response at week 24.Results. 82,5% of patients in the NTK group and 9.3% of patients in the placebo group achieved ACR20 at week 24 with the 95% CI [0,63; 0,84] (p < 0,0001). Skin manifestations and axial disease significantly improved with NTK. The safety profile of NTK was comparable to placebo. The most frequent treatment-related AEs were expected and common for all other IL-17 inhibitors: increased alanine aminotransferase (ALT), infections, lymphopenia.Conclusion. NTK in the dose of 120 mg has superior efficacy over placebo in patients with active psoriatic arthritis. The safety profile is consistent with other IL-17 inhibitors.

scholarly journals Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial

2021 ◽  
pp. annrheumdis-2021-221019
Author(s):  
Lars Erik Kristensen ◽  
Mauro Keiserman ◽  
Kim Papp ◽  
Leslie McCasland ◽  
Douglas White ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Adverse Events ◽  
Primary Endpoint ◽  
Study Drug ◽  
Signs And Symptoms ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Interleukin 23

ObjectiveTo evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD).MethodsIn the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing.ResultsAt week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug).ConclusionsRisankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD.Trial registration numberNCT03675308.

scholarly journals LB0001 EFFICACY AND SAFETY OF UPADACITINIB VERSUS PLACEBO AND ADALIMUMAB IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND INADEQUATE RESPONSE TO NON-BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS (SELECT-PsA-1): A DOUBLE-BLIND, RANDOMIZED CONTROLLED PHASE 3 TRIAL

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 16.2-17
Author(s):  
I. Mcinnes ◽  
J. Anderson ◽  
M. Magrey ◽  
J. F. Merola ◽  
Y. Liu ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Study Drug ◽  
Musculoskeletal Symptoms ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Research Support ◽  
Self Assessment ◽  
Double Blind ◽  
Biologic Dmard ◽  
Secondary Endpoints

Background:Upadacitinib (UPA) is an oral, reversible, JAK inhibitor approved for treatment of rheumatoid arthritis (RA) and currently under evaluation for treatment of psoriatic arthritis (PsA).Objectives:To assess the efficacy and safety of UPA vs placebo (PBO) and adalimumab (ADA) in patients (pts) with PsA and prior IR or intolerance to ≥1 non-biologic DMARD (non-bDMARD).Methods:Pts with active PsA (≥3 swollen and ≥3 tender joints), active or historical psoriasis, and on ≤2 non-bDMARDs were randomized 1:1:1:1 to once daily UPA 15 mg (UPA15), UPA 30 mg (UPA30), ADA 40 mg every other week, or PBO. The primary endpoint was the proportion of pts achieving ACR20 for UPA vs PBO at Wk 12. Multiplicity controlled secondary endpoints for each dose of UPA vs PBO included change in HAQ-DI, FACIT-F, and SF-36 PCS (Wk 12); static Investigator Global Assessment of Psoriasis of 0 or 1, PASI75, and change in Self-Assessment of Psoriasis Symptoms (Wk 16); change in modified Sharp/van der Heijde Score (mTSS), proportion of pts achieving MDA, and resolution of enthesitis (LEI=0) and dactylitis (LDI=0) (Wk 24). For each dose of UPA, the multiplicity-controlled analysis also included non-inferiority and superiority vs ADA for ACR20 and superiority for HAQ-DI and pt’s assessment of pain NRS (Wk 12). ACR50/70 at Wk 12 and ACR20 at Wk 2 were additional secondary endpoints. Treatment-emergent adverse events (TEAEs) through 24 wks are reported for pts who received ≥1 dose of study drug.Results:1705 pts were randomized; 1704 received study drug (53.2% female, mean age 50.8 yrs, mean duration of PsA diagnosis 6.1 yrs). 82% were on ≥1 concomitant non-bDMARD, of whom 84% received MTX +/- another non-bDMARD.At Wk 12, ACR20 rates were 70.6% with UPA15 and 78.5% with UPA30 vs 36.2% with PBO (p < .001 for UPA15/30 vs PBO) and 65.0% with ADA (non-inferiority, p < .001 for UPA15/30 vs ADA; superiority, p < .001 for UPA30 vs ADA). A greater proportion of pts achieved ACR50/70 with UPA15/30 vs PBO and UPA30 vs ADA. Improvements were observed with UPA15/30 vs PBO for all multiplicity controlled secondary endpoints and for UPA 15/30 vs ADA for HAQ-DI and UPA 30 vs ADA for improvement in pain (Figure 1A-1B). At Wk 24, change in mTSS was 0.25 for PBO, -0.04 for UPA15, 0.03 for UPA30, and 0.01 for ADA (p < 0.001 for UPA15/30 vs PBO). The rates of TEAEs and serious AEs, including serious infections, were similar in the PBO, UPA15, and ADA arms and higher with UPA30 (Figure 2). The rate of herpes zoster was similar for PBO and UPA15/30. No MACE was reported with UPA. One malignancy occurred in each of the PBO and UPA15 arms, and 3 malignancies were reported in each of the UPA30 and ADA arms. VTE were reported in 1 pt on PBO, 1 pt on UPA30, and 2 pts on ADA. One death occurred in the PBO arm.Conclusion:In this non-bDMARD-IR PsA population, treatment with UPA15/30 demonstrated improvement in musculoskeletal symptoms, psoriasis, physical function, pain, and fatigue and inhibited radiographic progression; improvements were observed by Wk 2. At Wk 12, UPA15/30 were non-inferior to ADA for ACR20, with superiority demonstrated for UPA30. Greater percentages of UPA vs PBO pts achieved stringent measures of disease control (MDA, ACR50/70, sIGA 0/1). No new safety signals were identified compared with the safety profile observed in RA.Disclosure of Interests:Iain McInnes: None declared, Jaclyn Anderson Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Marina Magrey Grant/research support from: Amgen, AbbVie, and UCB Pharma, Consultant of: Novartis, Eli Lilly, Pfizer, and Janssen, Joseph F. Merola Consultant of: Merck, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma, Yi Liu: None declared, Mitsumasa Kishimoto Consultant of: bbVie, Eli Lilly, Celgene, Pfizer, Gilead, Janssen, and UCB Pharma, Speakers bureau: AbbVie, Eisai, Celgene, Pfizer, Novartis, Eli Lilly, Tanabe-Mitsubishi, Ayumi, Janssen, Astellas, and UCB Pharma, Sławomir Jeka Speakers bureau: AbbVie, Pfizer, Roche, Novartis, MSD, Sandoz, Eli Lilly, Egis, UCB, Celgene, Cesar Francisco Pacheco Tena: None declared, xin wang Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Liang Chen Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Patrick Zueger Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Aileen Pangan Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, UCB, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai

scholarly journals Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study)

Rheumatology ◽  
2021 ◽  
Author(s):  
Frank Behrens ◽  
Michaela Koehm ◽  
Tanja Rossmanith ◽  
Rieke Alten ◽  
Martin Aringer ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Response Rate ◽  
Inadequate Response ◽  
Phase 3 ◽  
Double Blind ◽  
Efficacy Outcome ◽  
Clinical Benefits ◽  
Secondary Endpoints ◽  
The Difference ◽  
N 93

Abstract Objective To investigate the efficacy and safety of rituximab + LEF in patients with RA. Methods In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators’ control. Results Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders. Conclusion The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring. Trial registration EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958.

scholarly journals POS0928 NETAKIMAB EFFICACY IN ANTI-TNF-NAIVE AND ANTI-TNF-EXPERIENCED PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS: RESULTS OF SUBANALYSIS OF PHASE 3 ASTERA TRIAL

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 726.2-727
Author(s):  
S. Erdes ◽  
V. Mazurov ◽  
T. Dubinina ◽  
I. Gaydukova ◽  
A. Kundzer ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Phase Iii ◽  
P Value ◽  
Interleukin 17 ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Asas Criteria

Background:According to previous studies, the effectiveness of interleukin-17 (IL-17) inhibitors was higher in anti-TNF-naïve patients with ankylosing spondylitis (AS) [1,2]. Netakimab (NTK) is a humanized anti-IL-17A antibody approved for the treatment of AS, psoriatic arthritis, moderate-to-severe plaque psoriasis in Russia and Belarus.Objectives:To compare the efficacy of NTK in anti-TNF-naïve patients with anti-TNF-experienced patients with active AS at week 16 of therapy.Methods:ASTERA (NCT03447704) is an ongoing phase 3 placebo (PBO)-controlled clinical study, aimed at evaluating NTK efficacy in AS [3]. 228 adult patients with active AS (BASDAI ≥ 4) were randomly assigned (1:1) to receive 120 mg NTK or PBO subcutaneously at week 0,1,2 and then q2w. This analysis includes 112 patients in NTK group. Efficacy endpoints included ASAS20/40, ASAS5/6 and ASAS partial remission (PR) at week 16 of therapy.Results:28 (25.0%) of 112 patients in NTK group had previous inadequate response/intolerance to anti-TNF (anti-TNF-IR): 24 (21.4%) – one anti-TNF, and 4 (3.6%) – two anti-TNF. 84 (75.0%) patients were TNF-naive. Achievement of ASAS criteria response at week 16 was similar in both groups (Table 1).Table 1.Efficacy of NTK at week 16ParameterTNF-naïve (n = 84)anti-TNF-IR (n = 28)p-value*ASAS20, n (%)52 (61.9%)17 (60.7%)0.91ASAS40, n (%)35 (41.7%)11 (39.3%)0.82ASAS5/6, n (%)39 (46.4%)11 (39.3%)0.51ASAS(PR), n (%)15 (17.9%) 4 (14.3%)0.78*- Fisher’s exact testConclusion:NTK 120 mg provided sustained improvements in signs and symptoms of AS in anti-TNF-naive and anti-TNF-IR patients at 16 weeks of therapy.References:[1]Blair HA, Dhillon S. Secukinumab: A Review in Ankylosing Spondylitis. Drugs. 2016;76(10):1023-30.[2]Dougados M, et al. Efficacy and safety of ixekizumab through 52 weeks in two phase 3, randomised, controlled clinical trials in patients with active radiographic axial spondyloarthritis (COAST-V and COAST-W). Ann Rheum Dis. 2020;79(2):176-185.[3]Mazurov VI, et al. Efficacy and safety of Netakimab, anti-IL-17A monoclonal antibody, in patients with ankylosing spondylitis. Results of phase III international, multicenter, randomized double-blind clinical trial BCD-085-5/ASTERA. Nauchno-Practicheskaya Revmatologia=Rheumatology Science and Practice. 2020;58 (4):376–386 (In Russ).Acknowledgements:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Shandor Erdes: None declared, V Mazurov: None declared, Tatiana Dubinina: None declared, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad

scholarly journals Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Thomas P. Lodise ◽  
Mark Redell ◽  
Shannon O. Armstrong ◽  
Katherine A. Sulham ◽  
G. Ralph Corey
Keyword(s):  
Clinical Trials ◽  
Composite Endpoint ◽  
Outpatient Setting ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Skin Structure ◽  
Efficacy Outcome ◽  
End Of Treatment ◽  
Secondary Endpoints

Abstract Background The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. Methods SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7–10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. Results Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. Conclusions Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting.

scholarly journals Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

2019 ◽  
Vol 78 (6) ◽  
pp. 754-760 ◽  
Author(s):  
Sudha Visvanathan ◽  
Stefan Daniluk ◽  
Rafał Ptaszyński ◽  
Ulf Müller-Ladner ◽  
Meera Ramanujam ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Resorption ◽  
Primary Endpoint ◽  
Study Drug ◽  
Nuclear Factor Κb ◽  
Inadequate Response ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Autoantibody Production ◽  
Bone Resorption Markers

ObjectiveTo evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).MethodsIn total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Safety was assessed in patients who received at least one dose of study drug.ResultsAt week 12, the primary endpoint was not met, with 68.2% of patients treated with BI 655064 achieving an ACR20 vs 45.5% with placebo (p=0.064); using Bayesian analysis, the posterior probability of seeing a difference greater than 35% was 42.9%. BI 655064 was associated with greater changes in CD40–CD40L pathway-related markers, including reductions in inflammatory and bone resorption markers (interleukin-6, matrix metalloproteinase-3, receptor activator of nuclear factor-κB ligand), concentration of autoantibodies (immunoglobulin [Ig]G rheumatoid factor [RF], IgM RF, IgA RF) and CD95+ activated B-cell subsets. No serious adverse events (AEs) related to BI 655064 treatment or thromboembolic events occurred; reported AEs were mainly of mild intensity.ConclusionAlthough blockade of the CD40–CD40L pathway with BI 655064 in MTX-IR patients with RA resulted in marked changes in clinical and biological parameters, including reductions in activated B-cells, autoantibody production and inflammatory and bone resorption markers, with a favourable safety profile, clinical efficacy was not demonstrated in this small phase IIa study.Trial registration numberNCT01751776

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