scholarly journals Fosdagrocorat (PF-04171327) versus prednisone or placebo in rheumatoid arthritis: a randomised, double-blind, multicentre, phase IIb study

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000889 ◽  
Author(s):  
Frank Buttgereit ◽  
Vibeke Strand ◽  
Eun Bong Lee ◽  
Abraham Simon-Campos ◽  
Dorothy McCabe ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Double Blind ◽  
Multicentre Phase ◽  
Procollagen Type ◽  
Mediated Effects ◽  
American College Of Rheumatology ◽  
Primary Endpoints ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesGlucocorticoids have anti-inflammatory, transrepression-mediated effects, although adverse events (AEs; transactivation-mediated effects) limit long-term use in patients with rheumatoid arthritis (RA). We evaluated the efficacy and safety of fosdagrocorat (PF-04171327), a dissociated agonist of the glucocorticoid receptor, versus prednisone or placebo.MethodsIn this 12-week, phase II, randomised controlled trial, 323 patients with moderate to severe RA were randomised 1:1:1:1:1:1:1 to fosdagrocorat (1 mg, 5 mg, 10 mg or 15 mg), prednisone (5 mg or 10 mg) or placebo, once daily. The primary endpoints (week 8) were American College of Rheumatology 20% improvement criteria (ACR20) responses, and percentage changes from baseline in biomarkers of bone formation (procollagen type 1 N-terminal peptide [P1NP]) and resorption (urinary N-telopeptide to urinary creatinine ratio [uNTx:uCr]). Safety was assessed.ResultsACR20 responses with fosdagrocorat 10 mg and 15 mg were superior to placebo, and fosdagrocorat 15 mg was non-inferior to prednisone 10 mg (week 8 model-predicted ACR20 responses: 47%, 61%, 69% and 73% vs 51%, 71% and 37% with fosdagrocorat 1 mg, 5 mg, 10 mg and 15 mg vs prednisone 5 mg, 10 mg and placebo, respectively). Percentage changes from baseline in P1NP with fosdagrocorat 1 mg, 5 mg and 10 mg met non-inferiority criteria to prednisone 5 mg. Corresponding changes in uNTx:uCr varied considerably. All fosdagrocorat doses reduced glycosylated haemoglobin levels. AEs were similar between groups; 63 (19.5%) patients reported treatment-related AEs; 9 (2.8%) patients reported serious AEs. No patients had adrenal insufficiency, treatment-related significant infections or laboratory abnormalities. No deaths were reported.ConclusionIn patients with RA, fosdagrocorat 10 mg and 15 mg demonstrated efficacy similar to prednisone 10 mg and safety similar to prednisone 5 mg.Trial registration numberNCT01393639

scholarly journals A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis

2016 ◽  
Vol 76 (3) ◽  
pp. 566-570 ◽  
Author(s):  
Dae Hyun Yoo ◽  
Chang-Hee Suh ◽  
Seung Cheol Shim ◽  
Slawomir Jeka ◽  
Francisco Fidencio Cons-Molina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Concentration ◽  
Controlled Trial ◽  
Comparable Efficacy ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Maximum Serum ◽  
Primary Endpoints ◽  
Registration Number ◽  
Randomised Controlled

ObjectiveTo demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents.MethodsIn this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration–time curve from time zero to last quantifiable concentration (AUC0–last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24.Results103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%–125% (AUC0–last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles.ConclusionsCT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety.Trial registration numberNCT01534884.

scholarly journals Randomized, controlled trial of lasmiditan over four migraine attacks: Findings from the CENTURION study

Cephalalgia ◽  
2021 ◽  
Vol 41 (3) ◽  
pp. 294-304 ◽  
Author(s):  
Messoud Ashina ◽  
Uwe Reuter ◽  
Timothy Smith ◽  
Judith Krikke-Workel ◽  
Suzanne R Klise ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Study Drug ◽  
Statistical Testing ◽  
Control Group ◽  
Double Blind ◽  
Treatment Groups ◽  
Primary Endpoints ◽  
Registration Number ◽  
Secondary Endpoints ◽  
Common Teaes

Background We present findings from the multicenter, double-blind Phase 3 study, CENTURION. This study was designed to assess the efficacy of and consistency of response to lasmiditan in the acute treatment of migraine across four attacks. Methods Patients were randomized 1:1:1 to one of three treatment groups – lasmiditan 200 mg; lasmiditan 100 mg; or a control group that received placebo for three attacks and lasmiditan 50 mg for either the third or fourth attack. The primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in ≥2/3 attacks. Secondary endpoints included pain relief, sustained pain freedom and disability freedom. Statistical testing used a logistic regression model and graphical methodology to control for multiplicity. Results Overall, 1471 patients treated ≥1 migraine attack with the study drug. Both primary endpoints were met for lasmiditan 100 mg and 200 mg ( p < 0.001). All gated secondary endpoints were met. The incidence of treatment-emergent adverse events (TEAEs) was highest during the first attack. The most common TEAEs with lasmiditan were dizziness, paresthesia, fatigue, and nausea; these were generally mild or moderate in severity. Conclusions These results confirm the early and sustained efficacy of lasmiditan 100 mg and 200 mg and demonstrate consistency of response across multiple attacks. Trial Registration Number: NCT03670810

scholarly journals Safety and efficacy of subcutaneous tocilizumab in systemic sclerosis: results from the open-label period of a phase II randomised controlled trial (faSScinate)

2017 ◽  
Vol 77 (2) ◽  
pp. 212-220 ◽  
Author(s):  
Dinesh Khanna ◽  
Christopher P Denton ◽  
Celia J F Lin ◽  
Jacob M van Laar ◽  
Tracy M Frech ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Controlled Trial ◽  
Safety Data ◽  
Open Label ◽  
Double Blind ◽  
Skin Score ◽  
Open Label Extension ◽  
Registration Number ◽  
Randomised Controlled

ObjectivesAssess the efficacy and safety of tocilizumab in patients with systemic sclerosis (SSc) in a phase II study.MethodsPatients with SSc were treated for 48 weeks in an open-label extension phase of the faSScinate study with weekly 162 mg subcutaneous tocilizumab. Exploratory end points included modified Rodnan Skin Score (mRSS) and per cent predicted forced vital capacity (%pFVC) through week 96.ResultsOverall, 24/44 (55%) placebo-tocilizumab and 27/43 (63%) continuous-tocilizumab patients completed week 96. Observed mean (SD (95% CI)) change from baseline in mRSS was –3.1 (6.3 (–5.4 to –0.9)) for placebo and –5.6 (9.1 (–8.9 to–2.4)) for tocilizumab at week 48 and –9.4 (5.6 (–8.9 to –2.4)) for placebo-tocilizumab and –9.1 (8.7 (–12.5 to –5.6)) for continuous-tocilizumab at week 96. Of patients who completed week 96, any decline in %pFVC was observed for 10/24 (42% (95% CI 22% to 63%)) placebo-tocilizumab and 12/26 (46% (95% CI 27% to 67%)) continuous-tocilizumab patients in the open-label period; no patients had >10% absolute decline in %pFVC. Serious infection rates/100 patient-years (95% CI) were 10.9 (3.0 to 27.9) with placebo and 34.8 (18.0 to 60.8) with tocilizumab during the double-blind period by week 48 and 19.6 (7.2 to 42.7) with placebo-tocilizumab and 0.0 (0.0 to 12.2) with continuous-tocilizumab during the open-label period.ConclusionsSkin score improvement and FVC stabilisation in the double-blind period were observed in placebo-treated patients who transitioned to tocilizumab and were maintained in the open-label period. Safety data indicated increased serious infections in patients with SSc but no new safety signals with tocilizumab.Trial registration numberNCT01532869; Results.

scholarly journals Can topical epinephrine application to the papilla prevent pancreatitis after endoscopic retrograde cholangiopancreatography? Results from a double blind, multicentre, placebo controlled, randomised clinical trial

2021 ◽  
Vol 8 (1) ◽  
pp. e000562
Author(s):  
Adriana Fabiola Romano-Munive ◽  
J Jesus García-Correa ◽  
Luis F García-Contreras ◽  
José Ramírez-García ◽  
Luis Uscanga ◽  
...  
Keyword(s):  
Endoscopic Retrograde Cholangiopancreatography ◽  
Controlled Trial ◽  
Randomised Clinical Trial ◽  
Sterile Water ◽  
Endoscopic Retrograde ◽  
Double Blind ◽  
Registration Number ◽  
Baseline Characteristics ◽  
Randomised Controlled ◽  
Rectal Indomethacin

Background and study aimsPost-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a complication associated with important morbidity, occasional mortality and high costs. Preventive strategies are suboptimal as PEP continues to affect 4% to 9% of patients. Spraying epinephrine on the papilla may decrease oedema and prevent PEP. This study aimed to compare rectal indomethacin plus epinephrine (EI) versus rectal indomethacin plus sterile water (WI) for the prevention of PEP.Patients and methodsThis multicentre randomised controlled trial included patients aged >18 years with an indication for ERCP and naive major papilla. All patients received 100 mg of rectal indomethacin and 10 mL of sterile water or a 1:10 000 epinephrine dilution. Patients were asked about PEP symptoms via telephone 24 hours and 7 days after the procedure. The trial was stopped half way through after a new publication reported an increased incidence of PEP among patients receiving epinephrine.ResultsOf the 3602 patients deemed eligible, 3054 were excluded after screening. The remaining 548 patients were randomised to EI group (n=275) or WI group (n=273). The EI and WI groups had similar baseline characteristics. Patients in the EI group had a similar incidence of PEP to those in the WI group (3.6% (10/275) vs 5.12% (14/273), p=0.41). Pancreatic duct guidewire insertion was identified as a risk factor for PEP (OR 4.38, 95% CI (1.44 to 13.29), p=0.009).ConclusionSpraying epinephrine on the papilla was no more effective than rectal indomethacin alone for the prevention of PEP.Trial registration numberThis study was registered with ClinicalTrials.gov (NCT02959112).

scholarly journals Early and sustained efficacy with apremilast monotherapy in biological-naïve patients with psoriatic arthritis: a phase IIIB, randomised controlled trial (ACTIVE)

2018 ◽  
Vol 77 (5) ◽  
pp. 690-698 ◽  
Author(s):  
Peter Nash ◽  
Kamal Ohson ◽  
Jessica Walsh ◽  
Nikolay Delev ◽  
Dianne Nguyen ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Safety Profile ◽  
Controlled Trial ◽  
Health Assessment ◽  
Tender Joint ◽  
American College Of Rheumatology ◽  
Das 28 ◽  
Registration Number ◽  
Randomised Controlled

ObjectiveEvaluate apremilast efficacy across various psoriatic arthritis (PsA) manifestations beginning at week 2 in biological-naïve patients with PsA.MethodsPatients were randomised (1:1) to apremilast 30 mg twice daily or placebo. At week 16, patients whose swollen and tender joint counts had not improved by ≥10% were eligible for early escape. At week 24, all patients received apremilast through week 52.ResultsAmong 219 randomised patients (apremilast: n=110; placebo: n=109), a significantly greater American College of Rheumatology 20 response at week 16 (primary outcome) was observed with apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109) (P=0.025). Improvements in other efficacy outcomes, including 28-joint count Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and morning stiffness severity, were observed with apremilast at week 2. At week 16, apremilast significantly reduced PsA disease activity versus placebo, with changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index (P=0.001). Improvements were maintained with continued treatment through week 52. Over 52 weeks, apremilast’s safety profile was consistent with prior phase 3 studies in psoriasis and PsA. During weeks 0–24, the incidence of protocol-defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse event rates were 2.8% (apremilast) and 4.6% (placebo).ConclusionsIn biological-naïve patients with PsA, onset of effect with apremilast was observed at week 2 and continued through week 52. The safety profile was consistent with previous reports.Trial registration numberNCT01925768; Results.

scholarly journals Weekly iron–folic acid supplements containing 2.8 mg folic acid are associated with a lower risk of neural tube defects than the current practice of 0.4 mg: a randomised controlled trial in Malaysia

2020 ◽  
Vol 5 (12) ◽  
pp. e003897
Author(s):  
Kaitlyn L I Samson ◽  
Su Peng Loh ◽  
Siew Siew Lee ◽  
Dian C Sulistyoningrum ◽  
Geok Lin Khor ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Folic Acid Supplements ◽  
Registration Number ◽  
Menstruating Women ◽  
Iron Folic Acid ◽  
Randomised Controlled

IntroductionWeekly iron–folic acid (IFA) supplements are recommended for all menstruating women in countries where anaemia prevalence is >20%. Anaemia caused by folate deficiency is low worldwide, and the need to include folic acid is in question. Including folic acid might reduce the risk of a neural tube defect (NTD) should a woman become pregnant. Most weekly supplements contain 0.4 mg folic acid; however, WHO recommends 2.8 mg because it is seven times the daily dose effective in reducing NTDs. There is a reluctance to switch to supplements containing 2.8 mg of folic acid because of a lack of evidence that this dose would prevent NTDs. Our aim was to investigate the effect of two doses of folic acid, compared with placebo, on red blood cell (RBC) folate, a biomarker of NTD risk.MethodsWe conducted a three-arm double-blind efficacy trial in Malaysia. Non-pregnant women (n=331) were randomised to receive 60 mg iron and either 0, 0.4, or 2.8 mg folic acid once weekly for 16 weeks.ResultsAt 16 weeks, women receiving 0.4 mg and 2.8 mg folic acid per week had a higher mean RBC folate than those receiving 0 mg (mean difference (95% CI) 84 (54 to 113) and 355 (316 to 394) nmol/L, respectively). Women receiving 2.8 mg folic acid had a 271 (234 to 309) nmol/L greater mean RBC folate than those receiving 0.4 mg. Moreover, women in the 2.8 mg group were seven times (RR 7.3, 95% CI 3.9 to 13.7; p<0.0001) more likely to achieve an RBC folate >748 nmol/L, a concentration associated with a low risk of NTD, compared with the 0.4 mg group.ConclusionWeekly IFA supplements containing 2.8 mg folic acid increases RBC folate more than those containing 0.4 mg. Increased availability and access to the 2.8 mg formulation is needed.Trail registration numberThis trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619000818134).

scholarly journals Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study

2017 ◽  
Vol 77 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Josef S Smolen ◽  
Jung-Yoon Choe ◽  
Nenad Prodanovic ◽  
Jaroslaw Niebrzydowski ◽  
Ivan Staykov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transition Period ◽  
Phase Iii ◽  
Double Blind ◽  
Treatment Groups ◽  
American College Of Rheumatology ◽  
Registration Number ◽  
Phase Iii Study ◽  
Transition Study ◽  
To Receive

ObjectivesEfficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2.MethodsPatients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78.ResultsEfficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%–69.4% with INF/INF and 65.6%–68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively.ConclusionsThe efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2.Trial registration numberNCT01936181; EudraCT number: 2012-005733-37.

scholarly journals Naoxuekang, Xinnaoshutong and Xuesaitong capsules for treating stroke: a protocol for a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e015983 ◽  
Author(s):  
Huiling Chen ◽  
Hongbo Cao ◽  
Xu Guo ◽  
Meidan Zhao ◽  
Qing Xia ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Facial Paralysis ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Double Blind ◽  
Initial Treatment Period ◽  
Double Blind Clinical Trial ◽  
Registration Number ◽  
Index Value ◽  
Randomised Controlled

IntroductionAfter stroke, hemiplegia, dysphasia and facial paralysis can manifest during the convalescent period. Currently, no Chinese patent medicine (CPM) is previously reported to cure each of these symptoms primarily, and thus, there are no relevant instructions for the use of CPM. This study presents a new approach based on comparative effectiveness research to distinguish the curative effects of three CPMs that are often used in stroke convalescence to determine the ideal medicine for the treatment of each symptom.Methods and analysisIn this multicentre and double-blind clinical trial, stratified randomisation is used to group the patients according to their primary symptoms (hemiplegia, dysphasia and facial paralysis). Three strata will be enrolled, with 80 eligible participants included in each stratum. Each stratum will be randomly and equally divided into four groups, and each group will receive one of the following treatments: Naoxuekang, Xinnaoshutong (XNST), Xuesaitong (XST) or placebo. This study will include two stages: the initial treatment period (30 days) and a follow-up period (180 days). Three replicates for each data point will be completed during this trial. The first visit will occur on day 0 after enrolment, the second visit on day 30±2 and the third visit on day 210±5. The Delphi technique is adopted to achieve index weighting, which ensures that the evaluation outcome is patient oriented. The weighted index value will be computed as the final measurement index of the outcome.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of Tianjin University of Traditional Chinese Medicine (registration number TJUTCM-EC20160007). The results will be offered for publication in peer-reviewed journals.Trial registration numberThis trial was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-17010397). The date of registration was 11 January 2017.

scholarly journals Screening for and management of comorbidities after a nurse-led program: results of a 3-year longitudinal study in 769 established rheumatoid arthritis patients

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e000914 ◽  
Author(s):  
Laure Gossec ◽  
Martin Soubrier ◽  
Frantz Foissac ◽  
Anna Molto ◽  
Pascal Richette ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Wilcoxon Test ◽  
Paired Data ◽  
Registration Number ◽  
The Mean ◽  
Patient Advice ◽  
Randomised Controlled ◽  
Comorbidity Status

Background/purposeCardiovascular (CV) risk, cancer, infections and osteoporosis should be screened for in rheumatoid arthritis (RA). The objective was to assess 3-year effects of a nurse visit for comorbidity counselling.MethodsThis was an open long-term (3 years) extension of the Comorbidities and Education in Rheumatoid Arthritis 6-month randomised controlled trial in which patients with definite, stable RA were visiting a nurse for comorbidity counselling. Comorbidity status was assessed and nurses provided advice on screening and management, at baseline and 3 years later. A score was developed to quantify comorbidity screening and management: 0–100, where lower scores indicate better screening and management. The score was compared between baseline and 3-year assessment using a Wilcoxon test for paired data.ResultsOf the 970 recruited patients, 776 (80%) were followed-up at 2–4 years and 769 (79%) had available data for comorbidities at both time points: mean (±SD) age 58 (±11) years and mean disease duration 14 (±10) years; 614 (80%) were women, the mean Disease Activity Score 28 was 3.0±1.3, and 538 (70%) were receiving a biologic. At baseline, the mean comorbidity screening score was 36.6 (±19.9) and it improved at 3 years to 24.3 (±17.8) (p<0.0001), thus with a relative improvement of 33% (improvement of 12 points). CV risk screening, vaccination status and bone densitometry performance improved the most.ConclusionsComorbidity screening was suboptimal but improved notably over 3 years, after a nurse-led programme aiming at checking systematically for comorbidity screening and giving patient advice. This long-term efficacy pleads in favour of nurse-led interventions to better address comorbidities in RA.Trial registration numberNCT01315652

Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

2018 ◽  
Vol 77 (4) ◽  
pp. 495-499 ◽  
Author(s):  
Ronald F van Vollenhoven ◽  
Edward Clark Keystone ◽  
Vibeke Strand ◽  
Cesar Pacheco-Tena ◽  
Jiří Vencovský ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Biological Activity ◽  
Active Rheumatoid Arthritis ◽  
Controlled Trial ◽  
Inadequate Response ◽  
Acr20 Response ◽  
American College Of Rheumatology ◽  
Registration Number ◽  
Dose Dependent ◽  
Acr20 Response Rate

ObjectiveTo evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX).Methods321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48.ResultsAt week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation.ConclusionTreatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified.Trial registration numberNCT01999192; Results.

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