PSUMMIT-1
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Estudio primario

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A Phase 3 Multicenter, Randomized, Double-blind, Placebo controlled trial of

Registro de estudios EU Clinical Trials Register
Año 2009
Enlaces EUCTR - LV EUCTR - HU EUCTR - DE EUCTR - GB EUCTR - LT EUCTR - AT EUCTR - FI EUCTR - ES EUCTR - DK
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INTERVENTION: Product Name: ustekinumab Product Code: CNTO1275 Pharmaceutical Form: Solution for injection Current Sponsor code: ustekinumab Other descriptive name: Human Anti‐IL‐12 Antibody Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 90‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: Psoriatic Arthritis ; MedDRA version: 15.0 Level: LLT Classification code 10037160 Term: Psoriatic arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders PRIMARY OUTCOME: Main Objective: The primary objectives of this study are to evaluate the efficacy of ustekinumab in subjects with active PsA; by assessing the reduction in signs and symptoms of PsA and to evaluate the safety of ustekinumab in this population. Primary end point(s): The 2 coprimary endpoints are the proportion of subjects achieving an ACR 20 response at Week 24.; Secondary Objective: The secondary objectives of this study are to evaluate the efficacy of ustekinumab in:; 1. improving physical function;; 2. improving psoriatic skin lesions; and; 3. inhibiting the progression of structural damage. INCLUSION CRITERIA: Potential subjects must satisfy all of the following criteria to be enrolled in the study: • Men or women between 18 and 99 years of age, inclusive. • Have had PsA at least 6 months prior to the first administration of study agent. • Have a diagnosis of active PsA as defined by: – 5 or more swollen joints and 5 or more tender joints at screening and at baseline ‐AND‐ C‐reactive protein (CRP) = 0.3 mg/dL at screening. • Have at least 1 of the PsA subsets: DIP joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis. • Have active plaque psoriasis or a documented history of plaque psoriasis. • Have active PsA despite current or previous DMARD and/or NSAID therapy. DMARD therapy is defined as taking a DMARD for at least 3 months, or evidence of DMARD intolerance. NSAID therapy is defined as taking an NSAID for a

Estudio primario

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A Study of the Safety and Effectiveness of Ustekinumab in Patients With Psoriatic Arthritis

Registro de estudios clinicaltrials.gov
Año 2009
Enlaces Registro de estudios
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The purpose of this study is to evaluate the effectiveness (improvement of signs and symptoms) and safety of ustekinumab in participants with active psoriatic arthritis.

Estudio primario

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Efficacy and Safety of Ustekinumab in Patients with Active Psoriatic Arthritis: 2-Year Results from a Phase 3, Multicenter, Double-Blind, Placebo-Controlled Study

Autores Kavanaugh A , Puig L , Gottlieb AB
Revista Arthritis Rheum
Año 2013
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Estudio primario

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Ustekinumab in patients with active psoriatic arthritis: Results of the phase 3, multicenter, double-blind, placebo-controlled psummit I study

Conferencia Published in: Annals of the Rheumatic Diseases
Año 2013
Enlaces DOI www.cochranelibrary.com
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Objectives To assess efficacy and safety of UST in reducing signs and symptoms of active PsA in a large, multicenter, double-blind, placebo (PBO)-controlled, Ph3 trial. Methods Adult PsA pts (n=615) w/ active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL) despite DMARD and/or NSAIDs were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks, thereafter. At wk16, pts w/ <5% improvement in TJC & SJC entered blinded early escape (PBO$→ $UST45mg; UST45mg→90mg; 90mg→90mg). Stable concomitant MTX use was permitted but not mandated. Pts treated w/ prior anti-TNF agents were excluded. Primary endpoint was ACR20 response at wk24. Secondary endpoints at wk24 included: ACR 50/70, DAS28-CRP response, change from baseline (BL) in HAQ-DI, PASI75 response (in pts w/ ≥3% BSA involvement), and percent change from BL in enthesitis and dactylitis scores (in pts affected at BL). AEs are reported through the PBO-controlled period (wk16) and through wk24. Results Sig greater proportions of UST-than PBO-treated pts had ACR20 response at wk24 (Table). Sig improvements were also observed w/ UST45mg and 90mg for ACR50/70 responses and DAS28-CRP responses at wk24 vs PBO. The changes from BL in HAQ-DI at wk24 were sig greater in the UST than PBO grp, and sig greater proportions of UST-treated pts had a clinically meaningful change from BL in HAQ-DI (≥0.3). Nearly half used concomitant MTX at BL; this did not alter the likelihood of benefit of UST vs PBO. While ACR responses were greater w/ UST than PBO regardless of MTX use, differences were numerically larger among pts not taking MTX. Of 440pts w/ ≥3% BSA involvement at BL, sig larger proportion of UST pts achieved PASI 75 at wk24. Among pts affected w/ enthesitis (n=425) or dactylitis (n=286) at BL, sig greater improvements in enthesitis and dactylitis were observed at wk24 in the UST grp than PBO. Through wk16, the proportion of pts w/ ≥1 AE was similar between pts receiving UST (41.8%) and PBO (42.0%), w/ infections being the most common AE; 1.7% (UST) and 2.0% (PBO) had ≥1 serious AE. No malignancies, serious infections, TB, opportunistic infections, or deaths occurred through wk24. Conclusions In pts w/ active PsA,UST sig reduced the signs and symptoms of arthritis, improved physical function, enthesitis and dactylitis and improved plaque psoriasis vs PBO-treated pts at wk24. Safety profiles were similar between UST-and PBO-treated pts. (Table Presented).

Estudio primario

No clasificado

Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial.

Revista Lancet (London, England)
Año 2013
Enlaces Pubmed DOI
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BACKGROUND: Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. METHODS: In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). FINDINGS: Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). INTERPRETATION: Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. FUNDING: Janssen Research & Development.

Estudio primario

No clasificado

Ustekinumab improves arthritis-related and skin-related quality of life in patients with active psoriatic arthritis: Patient reported outcomes from randomized and double blinded phase III psummit I trial

Revista Value in Health
Año 2013
Enlaces DOI www.cochranelibrary.com
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OBJECTIVES: Examine impact of ustekinumab treatment on general &diseasespecific patient reported outcomes (PROs) of patients with active PsA using PSUMMIT1 data. METHODS: Adult PsA patients (n=615) with active disease despite DMARD&/or NSAID therapy were randomized to ustekinumab 45mg, 90mg, or PBO at wks0, 4, &q12wks, thereafter. Patients treated with prior anti- TNF agents were excluded. At wk16, patients with <5% improvement in SJC/TJC entered blinded EE (PBO→ustekinumab 45mg; ustekinumab 45mg→90mg; 90mg→90mg). PROs were measured with HAQ, DLQI, SF-36, &VAS for impact of PsA on work productivity (0-10), patient assessment of pain (0-10)& disease activity (0-10). ANOVA on van der Waerden normal scores was used for continuous variables & chi-square or the Cochran-Mantel-Haenszel (CMH) test for binary variables between groups. RESULTS: Baseline PRO measures indicated the study population had severe physical disability& impaired HRQoL, with mean HAQ score of 1.25 &mean DLQI score of ≥10. At wk24, greater improvements in: HAQ (0.31&0.4 vs. 0.1, P<0.001), DLQI (6.6&7.5 vs. 1.4, P<0.001), SF-36 PCS (4.9 &6.2 vs. 1.4, P<0.001)& MCS (3.4&4.8 vs. 1.5, p<0.01 90 mg only) were observed in ustekinumab 45mg &90mg groups vs PBO, respectively. Proportions of patients who achieved clinical meaningful improvements in HAQ ≥0.3 (47.8% &47.5% vs. 28.2%, P<0.001), DLQI ≥5 (58.6% &63.1% vs. 32.9%, P<0.001), &SF-36 PCS ≥5(46.5% &53.3% vs. 26.0%, P<0.001) &MCS ≥5(37.0% &47.7% vs. 33.7%, p<0.01 90mg only) were greater in ustekinumab 45mg &90mg group vs PBO, respectively. Ustekinumab 45mg&90mg -treated patients achieved greater improvements in patient assessment of pain (25.9% &29.6% vs. 4.5%, P<0.001), patient assessment of disease activity (25.4% &27.6% vs. 7.6%, P<0.001)& greater reduction in impact of disease on work productivity (1.82& 2.64 vs. 0.78, P<0.001) versus PBO-treated patients, respectively. CONCLUSIONS: Ustekinumab improves general as well as arthritis &skin-related QoL, &reduces the impact of disease on work productivity in patients with active PsA.

Estudio primario

No clasificado

Continued improvement of signs and symptoms in ustekinumab-treated patients with active psoriatic arthritis: Week 52 results of a phase 3, multicenter, double-blind, placebo-controlled study

Revista Annals of the Rheumatic Diseases
Año 2013
Enlaces DOI www.cochranelibrary.com
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Objectives We report safety & efficacy results through wk52 of PSUMMIT I, a large, multicenter, double-blind, PBO-controlled, Phase 3 trial of ustekinumab (UST) in pts with active psoriatic arthritis (PsA). Methods Adult PsA pts (n=615) with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12w. At wk16, pts with <5% improvement in TJC & SJC entered blinded early escape [EE] (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). Stable concomitant MTX use was permitted but not mandated. Pts treated with prior anti-TNF agents were excluded. PBO pts who did not EE began UST 45mg at wks 24, 28 and q12w. Unlike wk24, available data at wk52 were used for EE pts rather than counting them as nonresponders. AEs are reported through wk52. Results Improvement in clinical, joint, soft tissue, skin, and disability index increased notably from wk24 through wk52 (Table). The proportion of pts with ACR50 at wk24 vs. wk52 were 8.7%/38.0%, 24.9%/31.4%, 27.9%/37.0% for the PBO→UST, UST45mg, UST90mg groups, respectively. ACR responses were still numerically larger among pts not taking MTX at baseline vs. pts taking MTX at baseline. Of pts affected with enthesitis (n=425) or dactylitis (n=286) at baseline, improvements continued beyond wk24, with median percent changes at wk52 of -87.5, -83.3, -74.2 (enthesitis), and -100.00, -100.00, -100.00 (dactylitis) for the PBO→UST, UST45mg, and UST90mg groups, respectively). Mean duration of follow-up through wk52 was 29.75, 50.41, and 50.21wks for the PBO→UST45mg, UST45mg, and UST90mg groups, respectively The proportions of pts with ≥1 AE were 41.3%, 66.8%, and 64.7%, respectively; pts with ≥1 serious AE were 5.3%, 5.9%, and 3.4%; pts with ≥1 serious infection were 0.5%, 1.0%, and 1.0%. No malignancies, TB, opportunistic infections, or deaths occurred through wk52. There were 3 major cardiovascular adverse events reported after the PBO-controlled period in UST-treated pts. Conclusions In pts with active PsA, pts randomized to UST showed markedly reduced signs and symptoms of arthritis, improved physical function, enthesitis, and dactylitis, and alleviation of plaque psoriasis through wk52, at a rate similar to that reported for other biologic treatments through wk52. Safety was consistent with that observed during the PBO-controlled period with limited between-group differences.

Estudio primario

No clasificado

Ustekinumab improves physical function, quality of life and work productivity of patients with active psoriatic arthritis who were naïve to MTX, despite MTX therapy or previously treated with anti-TNF: Results from psummit I and psummit II

Revista Annals of the Rheumatic Diseases
Año 2013
Enlaces DOI www.cochranelibrary.com
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Objectives To examine the impact of ustekinumab (UST) treatment on patient reported outcomes in patients with active psoriatic arthritis (PsA) using week 24 data from two Phase 3 clinical studies, PSUMMIT I and II. Methods Adult patients with active PsA despite DMARD and/or NSAID therapy (PSUMMIT I, n=617) or previously treated with anti-TNFα therapy (PSUMMIT II, n=312) were randomized to receive UST 45mg, 90mg, or placebo (PBO) at wks 0, 4, and q12wks, thereafter. Patient reported outcomes were measured using the Health Assessment Questionnaire (HAQ), Dermatology Quality Life Index (DLQI), SF-36health survey questionnaire (SF-36), Visual Analogue Scales (VAS) for impact of PsA on work productivity (0-10), patient assessment of pain (0-10), and disease activity (0-10). Sub-analyses were conducted by combining both studies into 3 mutually exclusive groups based on treatment history: MTX naïve, previously treated with MTX therapy, and previously treated with anti-TNF therapy. Results At baseline, patients in both studies had moderate to severe physical disability and impaired health related quality of life with a mean HAQ score of ≥1.25, mean DLQI score of ≥10 and mean SF-36 PCS and MCS below 50 (normal population score). In PSUMMIT I, UST-treated patients achieved statistically significantly greater improvements in HAQ (- 0.31 and -0.4 vs. -0.1), DLQI (-6.6 and -7.5 vs. -1.4), and SF-36 PCS (4.9 and 6.2 vs. 1.4), for the UST 45mg, 90mg, vs. PBO groups, respectively. When compared to PBO, greater proportions of UST-treated patients achieved clinical meaningful improvements in HAQ (≥0.3) (47.8% and 47.5% vs. 28.2%), DLQI (≥5) (58.6% and 63.1% vs. 32.9%), and SF-36 PCS (≥5) (45.5%, and 53.3% vs. 26.0%), for the UST 45mg, 90mg, vs. PBO groups, respectively. Similar results were observed in PSUMMIT II and in the sub-analyses by MTX naïve, prior MTX experienced, and prior anti-TNFα experienced patients. Similar results were also observed in SF-36 sub-scales, especially in bodily pain and physical health. In the anti-TNF naïve population, statistically significantly greater improvement in SF-36 MCS was observed in the combined UST 45mg and 90mg group vs PBO Additionally, UST-treated patients achieved statistically significantly greater improvements in patient assessment of pain, patient assessment of disease activity, and greater reduction in impact of disease on work productivity vs PBO-treated patients. Conclusions UST improves physical function, improves general, arthritis and skin-related quality of life, and reduces the impact of disease on work productivity in patients with active PsA regardless of current or prior MTX use or prior anti-TNF experience.

Estudio primario

No clasificado

Ustekinumab in patients with active psoriatic arthritis: Results of the phase III, multicenter, double-blind, placebo-controlled PSUMMIT i study

Conferencia Published in: Journal of the American Academy of Dermatology
Año 2013
Enlaces DOI www.cochranelibrary.com
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Objective: To assess the efficacy and safety of ustekinumab (UST) in patients (pts) with psoriatic arthritis (PsA). Methods: Adult PsA pts (n = 615) with active disease (≥ 5 SJC and ≥ 5 TJC; CRP ≥ 0.3 mg/dL) despite DMARDs and/or NSAIDs were randomized to UST 45 mg (UST 45 mg), UST 90 mg (UST 90 mg), or PBO at weeks 0, 4, and q12 weeks. At week 16, pts with < 5% improvement in TJC and SJC entered blinded early escape (PBO -» UST 45 mg; UST 45 mg-»90 mg; 90 mg-»90 mg). Stable concomitant methotrexate (MTX) was permitted but not mandated. Patients treated with previous anti-TNF agents were excluded. Primary endpoint was ACR 20 response at week 24; secondary endpoints included: ACR 50 response, ACR 70 response, DAS28-CRP response, change from baseline in HAQ-DI, PASI 75 response (in pts with ≥ 3% BSA), and percent change from baseline in enthesitis and dactylitis scores (in pts affected at baseline). Results: At week 24, ACR 20 responses were 42.4%, 49.5%, and 22.8% for the UST 45 mg, UST 90 mg, and PBO groups, respectively (P < .001). Significant improvements were also observed with UST 45 mg and 90 mg vs PBO for ACR 50, ACR 70 and DAS28-CRP responses (all P < .001). Changes from baseline in HAQ-DI at week 24 were significantly greater in the UST vs PBO groups, and significantly greater proportions of UST-treated pts had a clinically meaningful change from baseline in HAQ-DI (≥0.3; all P < .001). Nearly half of the pts used concomitant MTX at baseline; this did not alter the benefit of UST vs PBO. While ACR responses were greater with UST vs PBO, regardless of MTX use, differences were numerically larger among pts not taking MTX. Of 440 pts with ≥ 3% BSA involvement at baseline, PASI 75 was achieved in 572%, 62.4%, and 11.0% in the UST 45 mg, UST 90 mg, and PBO groups, respectively (P <.001). Among pts with enthesitis (n = 425) or dactylitis (n = 286) at baseline, greater improvements in enthesitis and dactylitis were observed at week 24 in the UST groups vs PBO (P < .001, for each). Through week 16 (PBO-controlled period), proportion of pts with ≥ 1 AE was similar between UST (41.8%) and PBO (42.0%), with infections being the most common AE; 1.7% (UST) and 2.0% (PBO) had ≥ 1 serious AE. No malignancies, serious infections, TB, opportunistic infections, or deaths occurred through week 24. Conclusion: UST significantly reduced the signs and symptoms of arthritis, improved physical function, enthesitis and dactylitis, and plaque psoriasis vs PBO-treated pts at week 24. Safety profiles were similar between UST and PBO. Supported by Janssen Services, LLC.

Estudio primario

No clasificado

Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 2-year results from a phase 3, multicenter, double-blind, placebo-controlled study

Revista Annals of the Rheumatic Diseases
Año 2014
Enlaces DOI www.cochranelibrary.com
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Objectives To evaluate long-term clinical/radiographic efficacy of subcutaneous UST 45/90 mg in patients with active psoriatic arthritis (PsA) through wk108 of the PSUMMIT 1 trial. Methods Adult PsA pts (n=615) with active disease (≥5 SJC and ≥5 TJC;CRP≥0.3mg/dL) despite DMARD and/or NSAID therapy were randomized to receive UST45mg, 90mg, or PBO at wks 0, 4, and q12wks. At wk16, pts with <5% improvement in TJC & SJC entered blinded early escape (PBO$→ $UST45mg; UST45mg$→ $90mg; 90mg$→ $90mg). PBO-treated patients subsequently crossed over to UST45mg at wk24. Patients received q12wks dosing to wk88, with final efficacy evaluation at wk100 and safety assessment at wk108. Stable concomitant MTX use was permitted but not mandated. Pts treated with prior anti-TNF agents were excluded. Primary endpoint was ACR20 response at wk24. Other efficacy measures included ACR50, 70 responses, changes in HAQ-DI, and changes in vdHS-S scores. Patients who discontinued study agent due to efficacy-related reasons or who initiated protocol-prohibited medications were counted as non-responders. Otherwise, missing data were not imputed. Patients randomized to 45mg group who entered early escape to receive 90mg at wk 16 were included in the 45mg group in analyses. Results Through wk108, 79.7% of pts (490/615) completed study agent administration; 20.3% discontinued study agent [including 5.0% for adverse events, and 6.5% for lack of efficacy]. At wk24, significantly larger proportions of UST 45/90 mg pts had ACR20/50/70 responses, and greater improvements in HAQ-DI than PBO patients. Clinical improvements were generally maintained through wk100 (Table). Of 440pts with ≥3% BSA involvement at baseline, 63.9%, 72.5% and 71.3% of PBO$→ $ 45mg, 45mg and 90mg groups achieved PASI 75 at wk100. Wk24 analysis of PSUMMIT 1 demonstrated that UST treatment significantly inhibited radiographic progression at wk24 compared with PBO. Inhibition of radiographic progression was maintained at wk 52 and wk100 (Table). Through wk108, with average follow-up of 91.9 wks, rates (per 100pt-years of f/u) of AEs and serious AEs were 160.60 and 7.10, respectively, in the combined UST group. Rates of serious infections, malignancies, and major adverse cardiovascular events (MACE) were 1.23, 0.38, and 0.66, respectively, in the combined UST-treated group. The proportion of UST injections with injection-site reactions was 0.4%. Conclusions In PSUMMIT 1, q12 wk maintenance injections for both UST 45mg and UST 90mg maintained clinical efficacy through wk100. Effects on inhibition of radiographic progression were maintained through wk100. UST continues to be well tolerated and demonstrated a safety profile similar to that seen in PsO patients. (Figure Presented).

Estudio primario

No clasificado

Ustekinumab is effective in inhibiting radiographic progression in patients with active psoriatic arthritis: Integrated data analysis of two phase 3, randomized, placebo-controlled studies

Revista Annals of the Rheumatic Diseases
Año 2014
Enlaces DOI www.cochranelibrary.com
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Objectives To evaluate the effect of ustekinumab (UST), an IL-12/23 p40 inhibitor, on inhibition of progression of structural damage in patients with active psoriatic arthritis (PsA) at wk24 and wk52 in the PSUMMIT 1 and PSUMMIT 2 trials. Methods Adult PsA patients with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID therapy (PSUMMIT 1, n=615; PSUMMIT 2, n=132) or previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy (PSUMMIT 2, n=180) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks, thereafter. At wk16, patients with <5% improvement in TJC & SJC entered blinded early escape [EE] (PBO$→ $UST45mg; UST45mg$→ $90mg; 90mg$→ $90mg). No concomitant DMARDs with the exception of MTX (approximately 50% of patients in each study) were permitted. Radiographs of hands and feet were taken at wks 0, 24, and 52 regardless of EE status, or at the time of study drug discontinuation (unless radiographs were completed within the prior 8wks). Erosions and joint space narrowing (JSN) were evaluated by independent readers blinded to treatment, patient IDs and image time sequence using PsA modified van der Heijde-Sharp (vdH-S) method (total score ranging from 0-528). The major secondary endpoint of change from baseline in total vdH-S scores at wk24 was analyzed based on a pre-specified integrated data analysis using data combined from both studies. Imputation of missing data was done using linear extrapolation or median change of 0. Results Baseline disease characteristics including total vdH-S, TJC, SJC and CRP were comparable between PSUMMIT 1 & 2. In the integrated analyses, both UST 45 mg and 90 mg treated patients demonstrated a significant difference in change from baseline in total vdH-S scores at wk24 vs PBO (Table). Moreover, continued inhibition was demonstrated through wk 52; patients randomized to PBO who initiated UST at wk16 or 24 demonstrated slowing of radiographic progression by wk52 (mean change in total vdH-S wk24 to wk52 of 0.08). These observations were reproduced when PSUMMIT 1 was evaluated alone. In PSUMMIT 2, a demonstrable effect of UST on inhibition of structural damage progression could not be discerned; these results may have been impacted by missing radiographic data, especially among PBO-treated patients (23% missing radiographs). Conclusions Based upon the pre-specified integrated data analysis, ustekinumab inhibits radiographic progression at wk24. (Figure Presented).

Estudio primario

No clasificado

Ustekinumab improves physical function, general as well as arthritis-related and skinrelated quality of life and work productivity of patients with active psoriatic arthritis who were naive to MTX, despite MTX therapy or previously treated with anti-TNFalpha: results from PSUMMIT I and PSUMMIT II

Revista
Año 2014
Enlaces DOI www.cochranelibrary.com
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Background: To examine the impact of ustekinumab (UST) treatment on patient reported outcomes in patients with active PsA using week 24 data from two Phase 3 clinical studies, PSUMMIT I and II. Methods: Adult patients with active PsA despite DMARD and/or NSAID therapy (PSUMMIT I, n=617) or previously treated with anti‐ TNFalpha therapy (PSUMMIT II, n=312) were randomized to receive UST 45 mg, 90 mg, or placebo (PBO) at weeks 0, 4, and q12weeks, thereafter. Patient reported outcomes were measured using the Health Assessment Questionnaire (HAQ), Dermatology Quality Life Index (DLQI), SF‐36 health survey questionnaire (SF‐36), Visual Analogue Scales (VAS) for impact of PsA on work productivity (0‐10), patient assessment of pain (0‐10), and disease activity (0‐10). Sub‐analyses were conducted by combining both studies into 3 mutually exclusive groups based on treatment history: MTX naive, previously treated with MTX therapy, and previously treated with anti‐TNF therapy Results: At baseline, patients in both studies had moderate to severe physical disability and impaired health related quality of life with a mean HAQ score of >1.25, mean DLQI score of >10 and mean SF‐36 PCS and MCS below 50 (normal population score). In PSUMMIT I, UST‐treated patients achieved statistically significantly greater improvements in HAQ (‐0.31 and ‐0.4 vs ‐0.1), DLQI (‐6.6 and ‐7.5 vs ‐1.4), and SF‐36 PCS (4.9 and 6.2 vs 1.4), for the UST 45 mg, 90 mg, vs PBO groups, respectively . When compared with PBO, greater proportions of UST‐treated patients achieved clinical meaningful improvements in HAQ (>0.3) (47.8% and 47.5% vs 28.2%), DLQI (>5) (58.6% and 63.1% vs 32.9%), and SF‐36 PCS (>5) (45.5%, and 53.3% vs 26.0%), for the UST 45 mg, 90 mg, vs PBO groups, respectively. Similar results were observed in PSUMMIT II and in the sub‐analyses by MTX naive, prior MTX experienced, and prior anti‐ TNFalpha experienced patients. Similar results were also observed in SF‐ 36 sub‐scales, especially in bodily pain and physical health. In the anti‐ TNF naive population, statistically significantly greater improvement in SF‐36 MCS was observed in the combined UST 45mg and 90mg group vs PBO Additionally, UST‐treated patients achieved statistically significantly greater improvements in patient assessment of pain, patient assessment of disease activity, and greater reduction in impact of disease on work productivity vs PBO‐treated patients. Conclusion: UST improves physical function, improves general, arthritis and skin‐related quality of life, and reduces the impact of disease on work productivity in patients with active PsA regardless of current or prior MTX use or prior anti‐TNF experience.

Estudio primario

No clasificado

Early and sustained modified psarc response in psoriatic arthritis patients treated with ustekinumab: Results from psummit 1 and psummit 2

Revista Annals of the Rheumatic Diseases
Año 2014
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Background We have previously reported the efficacy and safety results of ustkeinumab (UST), an IL-12/23 p40 inhibitor, in patients with active psoriatic arthritis up to two years of UST treatment from the PSUMMIT 1 and PSUMMIT 2 trials. Objectives Here, we further describe the sustained effects of UST using the modified Psoriatic Arthritis Response Criteria (PsARC) response. Although not validated, the PsARC has been widely used in psoriatic arthritis clinical trials. Methods Adult PsA patients with active disease (≥5 SJC and ≥5 TJC; CRP≥0.3mg/dL [ULN 1.0 mg/dL]) despite DMARD and/or NSAID therapy (PSUMMIT 1, n=615; PSUMMIT 2, n=312 [of which 180 pts were previously treated with DMARD and/or NSAID, and prior anti-TNFα therapy]) were randomized to UST45mg, 90mg, or PBO at wks 0, 4, and q12wks, thereafter. PBO-treated pts were crossed over to UST45mg at wks24 and 28 followed by q12wk dosing. At wk16, patients with <5% improvement in TJC & SJC entered blinded early escape [EE] (PBO$→ $UST45mg; UST45mg$→ $90mg; 90mg$→ $90mg). No concomitant DMARDs with the exception of MTX (approximately 50% of patients in each study) were permitted. Patients were considered a responder using the modified PsARC if improvement was demonstrated in at least 2 (including at least 1 of the joint criteria) of the following criteria and no deterioration was noted in the other criteria: ≥30% decrease in the swollen joint count, ≥30% decrease in the tender joint count, ≥20% improvement in the patient's overall assessment (VAS), and ≥20% improvement in the physician's overall assessment (VAS). Proportions of patients with PSARC response were assessed at wks 4, 8, 12, 24, 28, 40, and 52. Results PSARC results are summarized in Table 1. Statistically significantly higher PSARC response rates were observed as early as wk4 for both UST groups compared to PBO in the PSUMMIT 1 trial and statistically significantly higher responses were also observed at wks 8, 12 and 24 for both UST dose groups compared to PBO in both trials. Responses in both UST dose groups continued to increase after wk24, reached a plateau at wk 28 and were maintained through wk52. Patients who were initially randomized to PBO and crossed over to 45mg achieved similar responses to those originally randomized to UST. Higher PSARC responses were consistently observed at wk8-24 for both UST groups compared with the placebo group regardless of baseline MTX status. The early onset of PSARC responses observed was consistent with early onset of ACR 20 responses. UST was generally well-tolerated. Conclusions Significantly higher PSARC responses were observed as early as wk4-8 for both UST dose groups compared with PBO. Improvements observed at wk24 continued to increase at wk28 and were sustained through wk52. (Figure Presented).

Estudio primario

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Maintenance of Clinical Efficacy and Radiographic Benefit Through Two Years of Ustekinumab Therapy in Patients With Active Psoriatic Arthritis: Results From a Randomized, Placebo-Controlled Phase III Trial.

Revista Arthritis care & research
Año 2015
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OBJECTIVE: To evaluate the efficacy and safety of ustekinumab through 2 years in adult patients with active psoriatic arthritis (PsA). METHODS: A total of 615 adult patients with active PsA were randomized to placebo, ustekinumab 45 mg, or ustekinumab 90 mg, at weeks 0, 4, and every 12 weeks through week 88 (last dose). At week 16, patients with <5% improvement in both tender and swollen joint counts entered blinded early escape (placebo to 45 mg, 45 mg to 90 mg, and 90 mg to 90 mg). All remaining placebo patients crossed over to ustekinumab 45 mg at week 24. Clinical efficacy measures included American College of Rheumatology criteria for 20% improvement (ACR20), Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), and ≥75% improvement in the Psoriasis Area and Severity Index (PASI75). Radiographic progression was evaluated using the modified Sharp/van der Heijde score (SHS). RESULTS: At week 100, ACR20, DAS28-CRP moderate/good response, and PASI75 rates ranged from 56.7-63.6%, 71.9-76.7%, and 63.9-72.5%, respectively, across the 3 treatment groups. In both ustekinumab groups, the median percent improvement in dactylitis and enthesitis was 100% at week 100. The mean changes in SHS score from week 52 to week 100 were similar to those observed from week 0 to week 52 in the ustekinumab groups. Through week 108, 70.7% and 9.7% of patients had an adverse event (AE) or serious AE, respectively. The rates and type of AEs were similar between the dose groups. CONCLUSION: Clinical and radiographic benefits from ustekinumab treatment were maintained through week 100 in the PSUMMIT 1 study. No unexpected safety events were observed; the safety profile of ustekinumab in this population was similar to that previously observed in psoriasis patients treated with ustekinumab.

Estudio primario

No clasificado

Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2).

Revista Annals of the rheumatic diseases
Año 2016
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OBJECTIVE: To evaluate ustekinumab efficacy and safety in psoriatic arthritis (PsA) patients with peripheral arthritis and physician-reported spondylitis (termed the 'spondylitis subset'). METHODS: Adults with active PsA (PSUMMIT-1/PSUMMIT-2, n=615/312) were randomised to ustekinumab 45 mg, 90 mg or placebo at week 0/week 4/q12 week. At week 16, patients with <5% improvement in tender and swollen joints entered blinded early escape. A subset of patients with physician-identified spondylitis was evaluated with spondylitis-specific assessments, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score employing C reactive protein (ASDAS-CRP), through week 24. RESULTS: 256/927 (27.6%) PSUMMIT-1/PSUMMIT-2 patients (placebo/ustekinumab, n=92/164) comprised the evaluable spondylitis subset. At week 24, in this analysis subset, significantly more patients achieved BASDAI20/50/70 responses (54.8%/29.3%/15.3% vs 32.9%/11.4%/0%; p≤0.002), improvement in BASDAI question 2 concerning axial pain (1.85 vs 0.24; p<0.001) and mean per cent ASDAS-CRP improvements (27.8% vs 3.9%; p<0.001) for ustekinumab versus placebo recipients, respectively. Comparable to the overall study population, significant improvements were also achieved in psoriasis, peripheral arthritis, enthesitis, dactylitis, physical function and peripheral joint radiographs in the spondylitis subset. CONCLUSIONS: In this post-hoc analysis of PsA patients with baseline peripheral arthritis and physician-reported spondylitis, ustekinumab-treated patients demonstrated significant improvements in axial signs and symptoms through week 24. TRIAL REGISTRATION NUMBER: PSUMMIT-1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT-2 (NCT01077362, EudraCT 2009-012265-60); post-study results.

Estudio primario

No clasificado

Ustekinumab Treatment and Improvement of Physical Function and Health-Related Quality of Life in Patients With Psoriatic Arthritis

Revista Arthritis care & research
Año 2016
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OBJECTIVE: To examine the effects of ustekinumab on patient‐reported outcomes (PROs) in PSUMMIT 1 and PSUMMIT 2 patients with active psoriatic arthritis (PsA) who were methotrexate (MTX) naive, MTX experienced, or anti‐tumor necrosis factor (TNF) experienced. METHODS: Patients in the phase 3, PSUMMIT 1 (n = 615) and PSUMMIT 2 (n = 312) studies randomly (1:1:1) received placebo, ustekinumab 45‐mg, or ustekinumab 90‐mg subcutaneous injections at weeks 0, 4, 16, 28, 40, and 52. The PROs (Health Assessment Questionnaire [HAQ] disability index [DI], Dermatology Life Quality Index [DLQI], 36‐Item Short Form [SF‐36] health survey physical (PCS) and mental component summary scores, patient assessments of pain and disease activity, and impact of disease on productivity) were assessed at weeks 0, 24, and 52. In these post hoc analyses, outcomes were compared between the ustekinumab and placebo groups for 3 mutually exclusive antecedent‐exposure populations from the combined studies: MTX/anti‐TNF naive (placebo, n = 56; 45 mg, n = 58; and 90 mg, n = 66), MTX experienced, biologic agent naive (placebo, n = 192; 45 mg, n = 190; and 90 mg, n = 185), and anti‐TNF experienced with or without MTX (placebo, n = 62; 45 mg, n = 60; and 90 mg, n = 58). RESULTS: At week 24, mean improvements from baseline in HAQ DI, DLQI, and SF‐36 PCS scores were significantly greater in both ustekinumab groups versus placebo across antecedent‐exposure groups. Greater proportions of ustekinumab‐treated than placebo‐treated patients (all P < 0.05) had clinically meaningful improvements in HAQ DI (≥0.3), DLQI (≥5), and SF‐36 (≥5) scores at week 24, irrespective of drug exposure. Improvements in pain, disease activity, and impact of disease on productivity were similar, and benefits were maintained through week 52. CONCLUSION: Significant improvements in PROs with ustekinumab versus placebo were observed in 3 antecedent‐exposure populations of PsA patients, including those with prior MTX and anti‐TNF use.

Estudio primario

No clasificado

Association between improvement in enthesopathy and quality of life: Results from anti-TNF-naïve patients with psoriatic arthritis in two phase 3 ustekinumab trials

Conferencia Published in: Annals of the Rheumatic Diseases
Año 2016
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Objectives: To assess the relationship between changes in enthesopathy and in function/health-related quality of life (HRQoL) in anti-TNF-naïve patients (pts) with psoriatic arthritis (PsA) receiving treatment with ustekinumab (UST). Methods: Adult pts in 2 Phase 3 trials (n=747 anti-TNF naive) with active PsA (≥5 SJC and ≥5 TJC;CRP≥0.3mg/dL) despite DMARD and/or NSAIDs were randomized to UST45mg, 90mg, or PBO at weeks 0, 4, and q12weeks. Stable concomitant MTX was permitted but not mandated. At week16, pts with <5% improvement in TJC & SJC entered blinded early escape (PBO→UST45mg; UST45mg→90mg; 90mg→90mg). Presence or absence of enthesopathy, HAQDI, and SF-36 were assessed at baseline and week 24. In this post-hoc analysis, enthesopathy of the Achilles tendon and plantar fascia was assessed as present or absent. Pts were categorized thereafter as follows: improved (enthesopathy present at baseline, but not at week 24), worsened (enthesopathy present at week 24, but not at baseline), and unchanged. Pts with an enthesopathy assessment missing at either time point were included in the unchanged category; those with enthesopathy data missing at both time points were excluded. Early escape pts were also excluded from this analysis. Improvements in HRQoL (assessed by the SF-36 PCS and MCS and physical function (HAQ-DI) were assessed by enthesopathy response category. Results: A total of 591 anti-TNF-naïve pts from both trials were included in the analysis; 45% of pts were female, mean age was 47 years, mean PsA duration was 6.7 years, and 74% had ≥3% body surface area affected at baseline. The proportion of pts with enthesopathy at baseline was similar in the combined UST (46.5%) and placebo (49.4%) groups. At week 24, the proportions of pts with enthesopathy were 22.8% and 35.9% for the combined UST and placebo groups, respectively. Across all pts, those who had an improvement in enthesopathy had a greater improvement in functioning and HRQoL, compared with those who did not (p<0.05; Table). When the analysis was restricted to those who achieved an ACR 20 response, pts with an improvement in enthesopathy showed a trend of greater improvement in functioning and HRQoL compared to those who had worsened (Table). Conclusions: There is an association between improvement in enthesopathy of the Achilles tendon and plantar fascia and improvement in physical function and quality of life in anti-TNF-naïve pts with PsA in 2 UST trials. Some, but not all, of this improvement may be explained by improvements in peripheral arthritis. (Table Presented).

Estudio primario

No clasificado

Responsiveness of Serum C-Reactive Protein, Interleukin-17A, and Interleukin-17F Levels to Ustekinumab in Psoriatic Arthritis: Lessons From Two Phase III, Multicenter, Double-Blind, Placebo-Controlled Trials.

Revista Arthritis & rheumatology (Hoboken, N.J.)
Año 2019
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OBJECTIVE: To evaluate the associations of C-reactive protein (CRP) and circulating Th17-associated cytokine levels with psoriatic arthritis (PsA) disease activity and therapeutic response to ustekinumab. METHODS: Interleukin-17A (IL-17A), IL-17F, IL-23, and CRP concentrations were measured in serum samples collected as part of the 2 PSUMMIT phase III studies of ustekinumab in PsA (n = 927). In post hoc analyses, relationships of IL-17A, IL-17F, and CRP levels at baseline, week 4, and week 24 with baseline skin and joint disease activity and response to therapy were evaluated using generalized linear models and Pearson's product-moment correlation tests. RESULTS: Baseline serum levels of IL-17A and IL-17F were positively correlated with baseline skin disease scores (r = 0.39-0.62). IL-23 levels were correlated with skin disease scores to a lesser extent (r = 0.26-0.31). No significant correlations were observed between these cytokine or CRP levels and baseline joint disease activity. There was no significant association of baseline levels of IL-17A, IL-17F, IL-23, or CRP with therapeutic response to ustekinumab in either the skin or joints. Significant reductions from baseline in levels of IL-17A, IL-17F, and CRP were seen in patients treated with ustekinumab compared to those treated with placebo. Ustekinumab-treated patients in whom 75% improvement in the Psoriasis Area and Severity Index score or 20% improvement according to the American College of Rheumatology criteria was achieved after 24 weeks of treatment had greater reductions in CRP level (geometric mean decreases of 51-58% versus 32-33%; P < 0.05), but not IL-17A or IL-17F levels, than nonresponders. CONCLUSION: Baseline serum IL-23/IL-17 levels correlated with skin, but not joint, disease activity, suggesting tissue-specific variation. However, neither baseline Th17-associated cytokine levels nor CRP level were predictive of therapeutic response to ustekinumab in the skin or joints, despite rapid reductions in their levels following ustekinumab therapy.

Estudio primario

No clasificado

Association Between Enthesitis and Health-related Quality of Life in Psoriatic Arthritis in Biologic-naive Patients from 2 Phase III Ustekinumab Trials.

Revista The Journal of rheumatology
Año 2019
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OBJECTIVE: Evaluate enthesitis, physical function, and health-related quality of life (HRQOL) among patients with psoriatic arthritis (PsA) who are naive to anti-tumor necrosis factor agents. METHODS: In PSUMMIT 1 and 2, patients with PsA were randomized to placebo or ustekinumab 45 mg or 90 mg. Enthesitis was assessed at weeks 0 and 24 (Maastricht Ankylosing Spondylitis Enthesitis Score). Assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 (SF-36) physical component summary/mental component summary (PCS/MCS), and American College of Rheumatology 20 (ACR20). RESULTS: At Week 24, 21 had worsened enthesitis, 158 had improved enthesitis, and 412 had unchanged enthesitis. Improved enthesitis was associated with improvements in HAQ-DI and SF-36 MCS. Results were similar for ACR20 responders and nonresponders. CONCLUSION: Improvement in enthesitis at Week 24 was associated with improvements in physical function/HRQOL regardless of ACR20 response.

Estudio primario

No clasificado

Efficacy of ustekinumab in biologic-naïve patients with psoriatic arthritis by prior treatment exposure and disease duration: Data from PSUMMIT 1 and PSUMMIT 2

Revista RMD open
Año 2019
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Objective To evaluate the efficacy of ustekinumab by prior treatment exposure and disease duration in tumour necrosis factor inhibitor (TNF)-naïve patients with psoriatic arthritis (PsA) in the PSUMMIT 1 and PSUMMIT 2 studies. Methods In the phase 3, randomised, placebo-controlled PSUMMIT 1 and PSUMMIT 2 studies, adults with active PsA for ≥6 months despite conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or non-steroidal anti-inflammatory drugs (NSAIDs) (PSUMMIT 1) or csDMARDs, NSAIDs and/or anti-TNF agents (PSUMMIT 2) were enrolled. Patients were randomised to subcutaneous injections of placebo, ustekinumab 45 mg or ustekinumab 90 mg at weeks 0 and 4 and every 12 weeks. Efficacy was assessed at week 24 using the American College of Rheumatology criteria and 28-joint count disease activity score using C reactive protein (DAS28-CRP); radiographical progression, enthesitis, and dactylitis were also assessed in this post hoc analysis. Results A total of 747 patients were included; all 747 were TNF-naïve, of which, 179 were methotrexate-naïve and TNF-naïve, and 146 were all csDMARD-naïve and TNF-naïve. At week 24, greater proportions of ustekinumab-treated patients had ≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/ACR50/ACR70) responses, DAS28-CRP response and DAS28-CRP remission versus placebo in all three prior-treatment populations, with similar differences between treatment groups. Greater proportions of ustekinumab-treated patients also had complete resolution of enthesitis and dactylitis at week 24 across the three prior-treatment populations. Mean changes from baseline in total van der Heijde-Sharp Score at week 24 were generally smaller for ustekinumab-treated patients versus placebo but were statistically significant only in the full TNF-naïve population. Response rates for ACR20/ACR50/ACR70 were similar for TNF-naïve patients with PsA durations of <1 year, ≥1 to <3 years, and ≥3 years. Conclusion Ustekinumab-treated patients demonstrated greater clinical response at week 24 compared with placebo regardless of prior treatment exposure and PsA disease duration.

Estudio primario

No clasificado

Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs.

Revista Drug safety
Año 2019
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INTRODUCTION: Theoretical risks of biologic agents remain under study. OBJECTIVE: The aim of this study was to integrate 1-year safety data from 12 ustekinumab registrational trials. METHODS: Patients had moderate-to-severe plaque psoriasis, active psoriatic arthritis (PsA) (± methotrexate), or moderate-to-severe Crohn's disease (CD; failed/intolerant of immunomodulators/corticosteroids). Psoriatic patients received subcutaneous ustekinumab 45/90 mg or placebo, generally at week 0, week 4, then every 12 weeks thereafter, while those with CD received a single intravenous ustekinumab dose (130 mg or weight range-based dosing of approximately 6 mg/kg) or placebo induction dose at week 0, followed by subcutaneous ustekinumab 90 mg at week 8 and every 8/12 weeks thereafter. The incidence rates of a priori-defined safety events were integrated post hoc (adjusted for duration of follow-up, reported per 100 patient-years [PYs]). RESULTS: Among 6280 enrolled patients, 5884 ustekinumab-treated patients (psoriasis: 3117; PsA: 1018; CD: 1749) contributed 4521 PYs versus 674 PYs in placebo-treated patients through year 1 (829 PYs and 385 PYs during 8- to 16-week controlled periods). Combined across diseases among ustekinumab- versus placebo-treated patients, respective incidences/100 PYs (95% confidence intervals) of infections were 125.4 (122.2-128.7) versus 129.4 (120.9-138.3) through year 1, and not meaningfully increased in patients who did versus those who did not receive methotrexate (92.5 [84.2-101.5] vs. 115.3 [109.9-121.0]), or significantly increased in patients who did versus those who did not receive corticosteroids (116.3 [107.3-125.9] vs. 107.3 [102.0-112.8]) at baseline. Major adverse cardiovascular events (0.5 [0.3-0.7] vs. 0.3 [0.0-1.1]), malignancies (0.4 [0.2-0.6] vs. 0.2 [0.0-0.8]), and deaths (0.1 [0.0-0.3] vs. 0.0 [0.0-0.4]) were rare across indications. CONCLUSIONS: Ustekinumab demonstrated a favorable and consistent safety profile across registrational trials in approved indications. TRIAL REGISTRATIONS: ClinicalTrials.gov identifier: NCT00320216, NCT00267969, NCT00307437, NCT00454584, NCT00267956, NCT01009086, NCT01077362, NCT00265122, NCT00771667, NCT01369329, NCT01369342, and NCT01369355.

Estudio primario

No clasificado

Effects of ustekinumab on spondylitis-associated endpoints in TNFi-naïve active psoriatic arthritis patients with physician-reported spondylitis: pooled results from two phase 3, randomised, controlled trials

Revista RMD open
Año 2020
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BACKGROUND: The interleukin‐12/23p40‐subunit‐inhibitor ustekinumab significantly improved spondylitis‐related symptoms through Week 24 in psoriatic arthritis (PsA) patients with peripheral arthritis and physician‐reported spondylitis (PA‐PRS) in PSUMMIT‐1&2. We further evaluated ustekinumab's effect on spondylitis‐related endpoints in PSUMMIT‐1&2 tumour necrosis factor‐inhibitor (TNFi)‐naïve patients with PA‐PRS. METHODS: Patients with active PsA (≥5 swollen and ≥5 tender joints, C‐reactive‐protein ≥ 3.0 mg/L) despite conventional (PSUMMIT‐1&2) and/or prior TNFi (PSUMMIT‐2) therapy received subcutaneous ustekinumab 45 mg, 90 mg or placebo (Week 0, Week 4, Week 16). Changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) neck/back/hip pain question (#2) and modified BASDAI (mBASDAI, excluding PA) scores and Ankylosing Spondylitis Disease Activity Score (ASDAS) responses were assessed at Weeks 12 and 24. RESULTS: The pooled PSUMMIT‐1&2, TNFi‐naïve (n=747), PA‐PRS (n=223) subset (158 with human‐leucocyte‐antigen (HLA)‐B27 results) presented with moderate‐to‐severe spondylitis‐related symptoms (mean BASDAI‐neck/back/hip pain‐6.51, mBASDAI‐6.54, BASDAI‐6.51, ASDAS‐3.81). Mean Week 24 changes were larger among ustekinumab than placebo‐treated patients for both neck/back/hip pain (‐1.99 vs ‐0.18) and mBASDAI (‐2.09 vs ‐0.59). Improvements in neck/back/hip pain and fatigue appeared numerically greater in HLA‐B27+ than HLA‐B27 ‐ patients; those for other domains were generally consistent. Greater proportions of ustekinumab versus placebo‐treated patients achieved ASDAS clinically important improvement at Week 24 (decrease ≥ 1.1; 49.6% vs 12.7%; nominal p<0.05). CONCLUSIONS: Improvements in BASDAI neck/back/hip pain and mBASDAI among ustekinumab‐treated, TNFi‐naïve, PsA patients with PA‐PRS were clinically meaningful and consistent across assessment tools. Numerically greater improvements in neck/back/hip pain in HLA‐B27+ than HLA‐B27 ‐ patients, noted in the context of similar overall mBASDAI improvements between the subgroups, suggest ustekinumab may improve disease activity in TNFi‐naïve PsA patients likely to exhibit axial disease. CLINICAL TRIAL REGISTRATION NUMBERS: PSUMMIT 1, NCT01009086; PSUMMIT 2, NCT01077362.

Estudio primario

No clasificado

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials.

Revista RMD open
Año 2021
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OBJECTIVE: To investigate serum protein expression in participants with psoriatic arthritis (PsA) and changes after guselkumab treatment. METHODS: Participants with PsA were treated with guselkumab or placebo in the DISCOVER-1 and DISCOVER-2 studies. Serum levels of acute phase reactants C reactive protein (CRP) and serum amyloid A (SAA) and inflammatory cytokines/chemokines were measured at weeks 0, 4 and 24 in 300 study participants and 34 healthy controls (HCs). The PSUMMIT studies measured serum interleukin (IL)-17A, IL-17F and CRP after ustekinumab treatment and levels with ustekinumab versus guselkumab treatment were compared. RESULTS: Baseline serum levels of CRP, SAA, IL-6, IL-17A and IL-17F were elevated in participants with active PsA vs HCs (p<0.05, geometric mean (GM) ≥40% higher). Baseline T-helper cell 17 (Th17) effector cytokines were significantly associated with baseline psoriasis but not joint disease activity. Compared with placebo, guselkumab treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F and IL-22 as early as week 4 and continued to decrease through week 24 (p<0.05, GM decrease from baseline ≥33%). At week 24, IL-17A and IL-17F levels were not significantly different from HCs, suggesting normalisation of peripheral IL-23/Th17 axis effector cytokines postguselkumab treatment. Reductions in IL-17A/IL-17F levels were greater in guselkumab-treated versus ustekinumab-treated participants, whereas effects on CRP levels were similar. CONCLUSION: Guselkumab treatment reduced serum protein levels of acute phase and Th17 effector cytokines and achieved comparable levels to those in HCs. In participants with PsA, reductions of IL-17A and IL-17F were of greater magnitude after treatment with guselkumab than with ustekinumab.