scholarly journals Post hoc analysis of ellipsoid zone changes beyond the central subfield in symptomatic vitreomacular adhesion patients from the OASIS trial

2021 ◽  
Vol 6 (1) ◽  
pp. e000648
Author(s):  
Swetha Bindu Velaga ◽  
Muneeswar Gupta Nittala ◽  
Michael S Ip ◽  
Luc Duchateau ◽  
SriniVas R Sadda
Keyword(s):  
Time Course ◽  
Vitreomacular Adhesion ◽  
Ellipsoid Zone ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Phase Iiib ◽  
The Status ◽  
Registration Number ◽  
Post Hoc ◽  
And Control

Background/aimsOASIS is a Phase IIIb trial (NCT01429441) assessing long-term outcomes in subjects with symptomatic vitreomacular adhesion (VMA). The purpose of this study is to report on the frequency, severity, location and time course of ellipsoid zone (EZ) alterations in ocriplasmin-treated and sham control eyes in the OASIS study.Methods220 patients (146 ocriplasmin, 74 sham) subjects with VMA were enrolled in this masked post hoc analysis phase IIIb, randomised, sham-controlled double-masked multicentre clinical trial. A masked post hoc analysis of OCT images was performed at the Doheny Image Reading Center from subjects enrolled in the OASIS trial. The status of the EZ band was assessed in three different macular regions: the central subfield (CS) (≤1 mm diameter), the parafoveal area (PAA) (>1 to ≤3 mm) and the perifoveal area (PEA) (>3 to ≤6 mm). The EZ band was rated as normal/intact, full thickness macular hole (FTMH), abnormal but continuous, discontinuous/disrupted or absent at visits from baseline (pretreatment) to week 1 (day 7), month 1 (day 28), month 3, month 6, month 12 and the final follow-up at month 24. EZ band status was compared in both study and control eyes.ResultsA total of 208 patients (138 ocriplasmin, 70 sham) were included in this analysis. At baseline, FTMH was present in 48.6%, 8.0%, 0% and 52.8%, 2.9%, 0% in the CS, PAA and PEA of the ocriplasmin and sham groups, respectively. The EZ was graded to be abnormal but continuous, discontinuous/disrupted or absent at Baseline in 21.0%, 4.3%, 2.8% in the CS, PAA and PEA, respectively, of the ocriplasmin group; and 12.9%, 10.0%, 4.3% in the CS, PAA and PEA of the sham group. For the ocriplasmin group in the PAA, this frequency increased to 6.6% at week 1, was 9.8% at month 1, but improved to 3.8% at month 3, and remained stable to 1.6% at month 24. These differences, however, were not statistically significant.ConclusionsOcriplasmin treatment for symptomatic VMA was associated with EZ abnormalities in a small percentage of patients that was best assessed in regions (PEA) relatively unaffected by the VM interface disease at baseline. The EZ abnormalities were apparent by week 1, persisted at month 1, and appeared to resolve in the majority of cases by month 3.Trial registration numberNCT01429441

scholarly journals Is high-sensitivity troponin, alone or in combination with copeptin, sensitive enough for ruling out NSTEMI in very early presenters at admission? A post hoc analysis performed in emergency departments

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e023994 ◽  
Author(s):  
Camille Chenevier-Gobeaux ◽  
Mustapha Sebbane ◽  
Christophe Meune ◽  
Sophie Lefebvre ◽  
Anne-Marie Dupuy ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
False Negative ◽  
High Sensitivity ◽  
Threshold Value ◽  
St Segment Elevation ◽  
Post Hoc Analysis ◽  
Registration Number ◽  
Post Hoc

ObjectivesCopeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters.SettingWe performed a post hoc analysis of three prospective studies that included patients who presented to the emergency department for chest pain onset (CPO) of less than 6 hours.Participants449 patients were included, in whom 12% had NSTEMI. CPO occurred <2 hours from ED presentation in 160, between 2 and 4 hours in 143 and >4 hours in 146 patients. The prevalence of NSTEMI was similar in all groups (9%, 13% and 12%, respectively, p=0.281).MeasuresDiagnostic performances of HS-cTn and copeptin at presentation were examined according to CPO. The discharge diagnosis was adjudicated by two experts, including cardiac troponin I (cTnI). HS-cTn and copeptin were blindly measured.ResultsDiagnostic accuracies of cTnI, cTnI +copeptin and HS-cardiac troponin T (HS-cTnT) (but not HS-cTnT +copeptin) lower through CPO categories. For patients with CPO <2 hours, the choice of a threshold value of 14 ng/L for HS-cTnT resulted in three false negative (Sensitivity 80%(95% CI 51% to 95%); specificity 85% (95% CI 78% to 90%); 79% of correctly ruled out patients) and that of 5 ng/L in two false negative (sensitivity 87% (95% CI 59% to 98%); specificity 58% (95% CI 50% to 66%); 52% of correctly ruled out patients). The addition of copeptin to HS-cTnT induced a decrease of misclassified patients to 1 in patients with CPO <2 hours (sensitivity 93% (95% CI 66% to 100%); specificity 41% (95% CI 33% to 50%)).ConclusionA single measurement of HS-cTn, alone or in combination with copeptin at admission, seems not safe enough for ruling out NSTEMI in very early presenters (with CPO <2 hours).Trial registration numberDC-2009–1052

scholarly journals Different eGFR Decline Thresholds and Renal Effects of Canagliflozin: Data from the CANVAS Program

2020 ◽  
Vol 31 (10) ◽  
pp. 2446-2456
Author(s):  
Megumi Oshima ◽  
Bruce Neal ◽  
Tadashi Toyama ◽  
Toshiaki Ohkuma ◽  
Qiang Li ◽  
...  
Keyword(s):  
Hemodynamic Effect ◽  
Effect Sizes ◽  
Sample Sizes ◽  
Clinical Trial Registry ◽  
Renal Outcomes ◽  
Link Type ◽  
Cardiovascular Assessment ◽  
Registration Number ◽  
Post Hoc

BackgroundTraditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes.MethodsTo assess whether eGFR declines <57% could detect canagliflozin’s effects on renal outcomes, we conducted a post hoc study comparing effects of canagliflozin versus placebo on composite renal outcomes using sustained 57%, 50%, 40%, or 30% eGFR reductions in conjunction with ESKD and renal death. Because canagliflozin causes an acute reversible hemodynamic decline in eGFR, we made estimates using all eGFR values as well as estimates that excluded early measures of eGFR influenced by the acute hemodynamic effect.ResultsAmong the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect.ConclusionsDeclines in eGFR <57% may provide robust estimates of canagliflozin’s effects on renal outcomes if the analysis controls for the drug’s acute hemodynamic effect.Clinical Trial registry name and registration number:CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.

Neutropenia analysis of venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia: Pooled data from VENICE-I and -II Phase IIIb trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20011-e20011
Author(s):  
Mary Ann Anderson ◽  
Matthew Steven Davids ◽  
Arnon P. Kater ◽  
Tara Cochrane ◽  
Fatih Demirkan ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Second Primary ◽  
Post Hoc Analysis ◽  
Pooled Data ◽  
Concurrent Use ◽  
Phase Iiib ◽  
Second Primary Malignancies ◽  
Post Hoc

e20011 Background: Neutropenia is a common hematologic Grade (Gr) 3+ adverse event (AE) recorded in patients with chronic lymphocytic leukemia (CLL) receiving venetoclax (VEN). In this analysis, we evaluated fixed duration VEN monotherapy given to patients with relapsed or refractory (R/R) CLL with and without pre-existing Gr3+ neutropenia. Methods: This post-hoc analysis pooled data from patients in the ongoing Phase 3b trials VENICE-I and VENICE-II with R/R CLL who had received ≥1 dose of VEN monotherapy (ramp-up to 400 mg QD). Gr4 hematologic AEs and Gr3+ neutropenia ( < 1000 cells/mm3) with infection or fever were managed using dose interruption/reduction. Granulocyte colony stimulating factor (G-CSF) was used in Gr3+ neutropenia. Results: At data cutoff (June 30, 2019), 44/468 (9%) patients had Gr3+ neutropenia at baseline (BL; Gr3+ neutropenia group), 80% of whom received G-CSF during the study vs 38% of those with < Gr3 neutropenia at BL ( < Gr3 neutropenia group). Median on-study duration for VEN was 20.2 months (range: 0.1–36.1). Median number of prior CLL therapies was 2 for both groups (range: 1–10). Serious infections were experienced by 10/44 (23%) and 69/424 (16%) of patients in the Gr3+ and < Gr3 neutropenia groups, respectively. The most common AEs leading to discontinuation overall were second primary malignancies (13/468; 3%). 5/468 (1%) patients in the total population discontinued due to neutropenia/febrile neutropenia. One case of Gr5 infection with concomitant Gr3 neutropenia was reported in the < Gr3 neutropenia group post-VEN discontinuation. See Table. Conclusions: In this large post-hoc analysis, discontinuation due to neutropenia was rare (1%) in the overall population and accounted for 3/11 AE discontinuations in the Gr3+ neutropenia group; 10 patients had a serious infection. Patients with pre-existing neutropenia can be managed on VEN, though concurrent use of G-CSF is likely to be required. Additional data to follow. Clinical trial information: NCT02756611; NCT02980731 . [Table: see text]

scholarly journals Intra-articular sprifermin reduces cartilage loss in addition to increasing cartilage gain independent of location in the femorotibial joint: post-hoc analysis of a randomised, placebo-controlled phase II clinical trial

2020 ◽  
Vol 79 (4) ◽  
pp. 525-528 ◽  
Author(s):  
Felix Eckstein ◽  
Jeffrey L Kraines ◽  
Aida Aydemir ◽  
Wolfgang Wirth ◽  
Susanne Maschek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Healthy Subjects ◽  
Cartilage Thickness ◽  
Cartilage Loss ◽  
Thickness Change ◽  
Post Hoc Analysis ◽  
Registration Number ◽  
Osteoarthritis Initiative ◽  
Post Hoc ◽  
Femorotibial Joint

ObjectivesIn the phase II FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses (FORWARD) study, sprifermin demonstrated cartilage modification in the total femorotibial joint and in both femorotibial compartments by MRI in patients with knee osteoarthritis. Here, we evaluate whether sprifermin reduces cartilage loss and increases cartilage thickness, independent of location.MethodsPatients were randomised 1:1:1:1:1 to three once-weekly intra-articular injections of 30 µg sprifermin every 6 months (q6mo); 30 µg sprifermin every 12 months (q12mo); 100 µg sprifermin q6mo; 100 µg sprifermin q12mo; or placebo. Post-hoc analysis using thinning/thickening scores and ordered values evaluated femorotibial cartilage thickness change from baseline to 24 months independent of location. Changes were indirectly compared with those of Osteoarthritis Initiative healthy subjects.ResultsThinning scores were significantly lower for sprifermin 100 µg q6mo versus placebo (mean (95% CI) difference: 334 µm (114 to 554)), with a cartilage thinning score similar to healthy subjects. Thickening scores were significantly greater for sprifermin 100 µg q6mo, 100 µg q12mo and 30 µg q6mo versus placebo (mean (95% CI) difference: 425 µm (267 to 584); 450 µm (305 to 594) and 139 µm (19 to 259), respectively) and more than doubled versus healthy subjects.ConclusionsSprifermin increases cartilage thickness, and substantially reduces cartilage loss, expanding FORWARD primary results.Trial registration numberNCT01919164.

scholarly journals Impact of HPV-16/18 AS04-adjuvanted vaccine on preventing subsequent infection and disease after excision treatment: post-hoc analysis from a randomized controlled trial

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Shuang Zhao ◽  
Shangying Hu ◽  
Xiaoqian Xu ◽  
Xun Zhang ◽  
Qinjing Pan ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Hpv Vaccination ◽  
Hpv Infection ◽  
Trial Registration ◽  
Subsequent Infection ◽  
Hpv 16 ◽  
Post Hoc Analysis ◽  
Adjuvanted Vaccine ◽  
Link Type ◽  
Post Hoc

Abstract Background It is widely acknowledged that HPV prophylactic vaccine could prevent new infections and their associated lesions among women who are predominantly HPV-naive at vaccination. Yet there still remains uncertainty about whether HPV vaccination could benefit to individuals who have undergone surgery for cervical disease. Methods This post-hoc analysis intends to focus on intent-to-treat participants who underwent excision treatment at baseline and the follow-up period in a phase II/III, double-blind, randomized trial (ClinicalTrials.gov, number NCT00779766) conducted in Jiangsu province, China. We evaluate the impact of HPV vaccination on preventing women from subsequent infection and cervical lesions (LSIL+ and CIN2+) after excision treatment. Results One hundred sixty-eight (vaccine, n = 87; placebo, n = 81) performed excisional treatment in this clinical trial. We observed a significant effect of vaccination on acquiring 14 high-risk HPV (HR-HPV) infection after treatment (vaccine efficacy: 27.0%; 95% CI 4.9, 44.0%). The vaccine efficacy against new infections after treatment for 14 HR-HPV infection was estimated as 32.0% (95%CI 1.8, 52.8%), and was 41.2% (95%CI -162.7, 86.8%) for HPV16/18 infection. The accumulative clearance rates of the vaccine group and placebo group were 88.9 and 81.6% for HPV16/18 infection (P = 0.345), 63.4, 48.7% for 14 HR-HPV infection (P = 0.062), respectively. No significant difference was observed on the persistent rate of HPV16/18, 14 HR-HPV infection and occurrence rate of LSIL+ between the two groups. Conclusions No significant evidence from this study showed that HPV-16/18 AS04-adjuvanted vaccine could lead to viral faster clearance or have any effect on the rates of persistent infection among women who had excision treatment. However, the vaccine may still benefit post-treatment women with “primary prophylactic” effect. Further research is required in clarifying the effect of using the prophylactic HPV vaccine as therapeutic agents. Trial registration ClinicalTrials.gov identifier: NCT00779766. Date and status of trial registration: October 24, 2008. Completed; Has Results.

scholarly journals Onset of efficacy and duration of response of galcanezumab for the prevention of episodic migraine: a post-hoc analysis

2019 ◽  
Vol 90 (8) ◽  
pp. 939-944 ◽  
Author(s):  
Peter J Goadsby ◽  
David W Dodick ◽  
James M Martinez ◽  
Margaret B Ferguson ◽  
Tina M Oakes ◽  
...  
Keyword(s):  
Migraine Headache ◽  
Episodic Migraine ◽  
Preventive Effect ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Hoc Analysis ◽  
Duration Of Response ◽  
Registration Number ◽  
Post Hoc ◽  
Sustained Responses

Background and objectiveAs new migraine prevention treatments are developed, the onset of a preventive effect, how long it is maintained and whether patients initially non-responsive develop clinically meaningful responses with continued treatment can be assessed.MethodsAnalyses were conducted post-hoc of a double-blind, placebo-controlled, phase II-a study in patients with episodic migraine receiving galcanezumab 150 mg or placebo biweekly for 12 weeks (Lancet Neurol 13:885, 2014). The number of migraine headache days per week, and onset of efficacy measured as the first week galacanezumab separated from placebo were determined. Patients with ≥50%, ≥75% and 100% reduction in migraine headache days from baseline at months 1, 2 and 3 were calculated and defined as sustained responses. Non-responders (<50% response) at month 1 or 2 who then showed ≥50%, ≥75% and 100% response at later time-points were calculated.ResultsPatients were randomised to galcanezumab (n=107) or placebo (n=110). A significant (p=0.018) change of −0.89±0.11 (galcanezumab) vs −0.53±0.11 (placebo) migraine headache days indicated onset at week 1. Forty-seven per cent of galcanezumab and 25% of placebo patients responding at month 1 maintained response through months 2 and 3. Of non-responders at month 1, 27% on galcanezumab and 20% on placebo responded on months 2 and 3, and 50% of galcanezumab non-responders in months 1 and 2 responded on month 3, vs 24% on placebo.ConclusionsThe onset of efficacy of galcanezumab is within 1 week in a majority of patients, and patients receiving galcanezumab are twice more likely to maintain responses than placebo patients. Early non-responders may respond by month 2 or month 3.Trial registration numberNCT01625988.

Timing and Magnitude of Initial Change in Disease Activity Score 28 Predicts the Likelihood of Achieving Low Disease Activity at 1 Year in Rheumatoid Arthritis Patients Treated with Certolizumab Pegol: A Post-hoc Analysis of the RAPID 1 Trial

2012 ◽  
Vol 39 (7) ◽  
pp. 1326-1333 ◽  
Author(s):  
DÉSIRÉE VAN DER HEIJDE ◽  
EDWARD C. KEYSTONE ◽  
JEFFREY R. CURTIS ◽  
ROBERT B. LANDEWÉ ◽  
MICHAEL H. SCHIFF ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Certolizumab Pegol ◽  
Activity Score ◽  
Clinical Trial Registration ◽  
Low Disease Activity ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Post Hoc

Objective.To determine the relationship between timing and magnitude of Disease Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not reached) during the first 12 weeks of treatment with certolizumab pegol (CZP) plus methotrexate, and the likelihood of achieving low disease activity (LDA) at 1 year in patients with rheumatoid arthritis.Methods.In a post-hoc analysis of the RAPID 1 study, patients achieving LDA [DAS28(ESR) ≤ 3.2] at Year 1 were assessed according to DAS28 nonresponse at various timepoints within the first 12 weeks.Results.Seven-hundred eighty-three patients were included (CZP 200 mg, n = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group had a DAS28 improvement of ≥ 1.2 by Week 12. Of the 13.1% of patients with DAS28 improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA at Year 1 depended on timing of nonresponse — 22.3%, 8.4%, and 2.0% of patients with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year 1 — and magnitude of initial lack of DAS28 improvement; for example, compared with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6 had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively).Conclusion.Failure to achieve improvement in DAS28 within the first 12 weeks of therapy was predictive of a low probability of achieving LDA at Year 1. Moreover, the accuracy of the prediction was found to be strongly dependent on the magnitude and timing of the lack of the response. (Clinical Trial Registration Nos. NCT00152386 and NCT00175877).

scholarly journals POS1025 TOFACITINIB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS AND PROBABLE DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF TWO PHASE 3 CLINICAL TRIALS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 782.1-782
Author(s):  
L. Gossec ◽  
G. Citera ◽  
A. Sellas-Fernández ◽  
D. C. Gruben ◽  
M. Valderrama ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Research Support ◽  
Phase 3 ◽  
Two Phase ◽  
Post Hoc Analysis ◽  
Link Type ◽  
Sf 36 ◽  
Global Pain ◽  
Post Hoc

Background:Depression and anxiety are highly prevalent in patients (pts) with psoriatic arthritis (PsA),1 with inflammation a key pathogenic feature of depression in these pts.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. It acts by modulating immune and inflammatory responses. The link between major depressive disorder/generalised anxiety disorder (MDD/GAD), inflammation and tofacitinib effectiveness has not been fully explored.Objectives:Analyse the prevalence of probable MDD/GAD in pts with PsA initiating tofacitinib treatment and the impact of baseline (BL) probable MDD/GAD status on tofacitinib efficacy in these pts.Methods:This was a post hoc analysis of data from pts who received tofacitinib 5 or 10 mg twice daily (BID), or placebo (PBO), pooled from two Phase 3 trials (12-month OPAL Broaden [NCT01877668];3 6-month OPAL Beyond [NCT01882439]4). Pts with BL probable MDD and/or GAD were identified by a Short Form-36 Health Survey (SF-36) Mental Component Summary score (MCS) ≤38. Pt demographics/BL characteristics and outcomes were stratified by the presence (SF-36 MCS ≤38) or absence (SF-36 MCS >38) of BL probable MDD/GAD. At Months (M)3/6/9/12, changes from BL in SF-36 MCS were evaluated, and efficacy assessed by the proportions of pts who achieved: Psoriatic Arthritis Disease Activity Score (PASDAS) ≤3.2, Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement ≥0.35 and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) improvement ≥4. BL global pain was measured via visual analogue scale.Results:Of the 706 pts included in this analysis, BL probable MDD/GAD was identified in 46.2%, 44.9% and 46.2% of pts in the tofacitinib 5 mg BID (108/234), tofacitinib 10 mg BID (106/236) and PBO (109/236) groups, respectively. BL disease activity was similar across the three treatment groups, independent of probable MDD/GAD status (mean PASDAS: 6.1–6.4 in pts with vs 5.8–6.1 in pts without probable MDD/GAD). In the tofacitinib 5 mg BID group, mean BL scores for HAQ-DI (1.4 vs 1.0), FACIT-F total score (20.5 vs 32.4) and global pain (61.3 vs 51.5) indicated worse disability, fatigue and pain, respectively, for pts with vs without BL probable MDD/GAD. Similar findings were seen in the tofacitinib 10 mg BID and PBO groups. At M3, improvements from BL in SF-36 MCS in pts with probable MDD/GAD were numerically, but not significantly, greater with tofacitinib 5 and 10 mg BID vs PBO, and these changes were largely sustained to M12 (Figure 1a). At M3, numerically greater proportions of pts achieved improvements in PASDAS, HAQ-DI and FACIT-F with tofacitinib 5 or 10 mg BID vs PBO, regardless of BL probable MDD/GAD status (Figure 1b–d). Through M3–12, the proportions of pts who achieved PASDAS ≤3.2 with tofacitinib 5 or 10 mg BID were generally significantly greater in pts without vs with probable MDD/GAD (Figure 1b). At all timepoints, rates of improvement in HAQ-DI with tofacitinib 5 mg BID were numerically greater in pts with vs without probable MDD/GAD, whereas the opposite was true for tofacitinib 10 mg BID (Figure 1c). FACIT-F improvement rates with tofacitinib 10 mg BID were consistently numerically greater in pts with vs without probable MDD/GAD, while findings were mixed for tofacitinib 5 mg BID (Figure 1d).Conclusion:Around 46% of pts with PsA treated with tofacitinib had BL probable MDD/GAD (SF-36 MCS ≤38). Pts with BL probable MDD/GAD treated with tofacitinib had sustained changes in SF-36 MCS. Rates of clinical improvement with tofacitinib were generally greater in pts without vs with probable MDD/GAD, whereas findings for disability and fatigue improvements varied between tofacitinib doses. Further research is required to evaluate the relationship between PsA and depression, to improve treatment targets and the quality of life of pts with PsA.References:[1]Zhao et al. Clin Rheumatol 2020; 39: 217-225.[2]Mathew & Chandran. Rheumatol Ther 2020; 7: 287-300.[3]Mease et al. N Engl J Med 2017; 377: 1537-1550.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Deeks, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Laure Gossec Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Gustavo Citera Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis, Pfizer Inc, Sanofi Genzyme, Agustí Sellas-Fernández: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Monica Valderrama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Susana Gómez Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

scholarly journals Ixekizumab, with or without concomitant methotrexate, improves signs and symptoms of PsA: week 52 results from Spirit-P1 and Spirit-P2 studies

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Bernard Combe ◽  
Tsen-Fang Tsai ◽  
J. Eugene Huffstutter ◽  
Aubrey Trevelin Sprabery ◽  
Chen-Yen Lin ◽  
...  
Keyword(s):  
Signs And Symptoms ◽  
Inadequate Response ◽  
Efficacy And Safety ◽  
Stable Dose ◽  
Post Hoc Analysis ◽  
Sustained Efficacy ◽  
Link Type ◽  
American College Of Rheumatology ◽  
Post Hoc ◽  
Necrosis Factor

Abstract Background The efficacy and safety of ixekizumab (IXE) with and without continuous concomitant methotrexate (MTX), for up to 52 weeks of treatment, were evaluated in patients with active psoriatic arthritis (PsA). Methods Patients with active PsA who were biologic-naive (SPIRIT-P1) or had prior inadequate response to tumor necrosis factor inhibitors (SPIRIT-P2) were randomized to 80 mg IXE every 4 (IXE Q4W) or 2 weeks (IXE Q2W), after a 160-mg initial dose. In this post hoc analysis, efficacy and safety were assessed up to week 52 in the subgroups of patients who received (i) IXE as monotherapy and (ii) IXE along with a stable dose of MTX (no dose tapering or increase). Efficacy outcomes included, but were not limited to, the percentage of patients achieving the American College of Rheumatology (ACR) responses. Results Out of 455 patients initially randomized to IXE, 177 (38.9%) received monotherapy, 230 (50.5%) had concomitant MTX use, and 48 (10.5%) had other concomitant medication. Overall, 183 (40.2%) received IXE with a stable dose of concomitant MTX for 1 year. At week 52, the percentage of patients achieving ACR20/50/70 responses in IXE Q4W monotherapy versus concomitant MTX groups were 66.3% versus 55.3%, 48.4% versus 38.8%, and 35.8% versus 27.1%, respectively; these responses were generally similar with IXE Q2W. The safety profiles were similar between patients receiving IXE with or without concomitant MTX. Conclusions In this post hoc analysis, treatment with IXE demonstrated sustained efficacy in patients with PsA up to 1 year of treatment, with or without concomitant MTX therapy. Trial registration ClinicalTrials.gov NCT01695239 and NCT02349295.

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