scholarly journals P336 Association between the prior duration of remission and efficacy outcomes in patients with Ulcerative Colitis treated with tofacitinib 10 mg twice daily who were in stable remission and either dose-reduced to tofacitinib 5 mg twice daily or remained on 10 mg twice daily: 6-month data from the double-blind, randomised RIVETING study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S361-S362
Author(s):  
M C Dubinsky ◽  
G R D’Haens ◽  
W J Sandborn ◽  
S C Ng ◽  
J Panés ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dose Reduction ◽  
Small Sample Size ◽  
Small Sample ◽  
Open Label ◽  
Double Blind ◽  
Treatment Groups ◽  
Mayo Score ◽  
Remission Duration ◽  
To Receive

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). RIVETING (NCT03281304) is an ongoing, double-blind, randomised, parallel-group study designed to evaluate the efficacy and safety of dose reduction to tofacitinib 5 mg twice daily (BID) vs remaining on 10 mg BID in patients (pts) with UC in stable remission on tofacitinib 10 mg BID maintenance therapy. Eligible pts had received tofacitinib 10 mg BID for ≥2 consecutive years in an open-label, long-term extension study (NCT01470612), and had been in stable remission for ≥6 months (M) and corticosteroid-free for ≥4 weeks prior to enrolment.1 We aimed to evaluate the association between the duration of remission prior to enrolment into RIVETING and the efficacy of tofacitinib 5 and 10 mg BID. Methods Pts who were in partial Mayo score (PMS) remission (a PMS of ≤2 with no individual subscore >1, and a rectal bleeding subscore of 0) at RIVETING baseline were included in this analysis. Pts were randomised to dose-reduce to tofacitinib 5 mg BID or remain on 10 mg BID. We evaluated efficacy endpoints at Month 6 in RIVETING, stratified by duration of PMS remission (0–12, 12–24, 24–36, 36–48, >48 M) at RIVETING baseline. Results At RIVETING baseline, 139 of 140 pts were in PMS remission: 69 pts dose-reduced to tofacitinib 5 mg BID and 70 pts remained on tofacitinib 10 mg BID. In both treatment groups, compared with pts with <24M of PMS remission, baseline modified Mayo and total Mayo scores were numerically lower in pts with a PMS remission duration of >24M; these pts also generally had a numerically lower change from baseline modified Mayo and total Mayo scores at Month 6 (Table). At Month 6, following dose reduction to tofacitinib 5 mg BID, PMS remission was maintained in 66.7%, 60.0%, 82.4%, 75.0% and 90.0% of pts with baseline PMS remission durations of 0–12M, 12–24M, 24–36M, 36–48M and >48M, respectively. Corresponding values for pts who continued to receive tofacitinib 10 mg BID were 80.0%, 88.9%, 91.7%, 100.0% and 100.0%. At Month 6, the proportion of pts achieving modified Mayo remission, remission and modified PMS remission was generally higher in pts with baseline PMS remission of >24M vs pts with PMS remission of <24M across treatment groups (Table). Conclusion Following dose reduction from tofacitinib 10 to 5 mg BID, rates of modified Mayo remission, remission and PMS remission were numerically higher in pts with a PMS remission duration of >24M vs pts with <24M of PMS remission duration. The same trend was observed in pts who continued to receive tofacitinib 10 mg BID. These analyses are post hoc and limited by the small sample size. Reference

scholarly journals P409 Non-invasive predictors of maintaining remission in patients with moderately to severely active Ulcerative Colitis treated with tofacitinib who dose-reduced from tofacitinib 10 mg twice daily to 5 mg twice daily: 6-month data from the double-blind, randomised RIVETING study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S416-S417
Author(s):  
G R D’Haens ◽  
M C Dubinsky ◽  
M Regueiro ◽  
G O Santana ◽  
J Torres ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dose Reduction ◽  
Small Sample Size ◽  
Small Sample ◽  
Open Label ◽  
Double Blind ◽  
Faecal Calprotectin ◽  
Reactive Protein ◽  
Mayo Score ◽  
Over Time

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). RIVETING (NCT03281304) is an ongoing, double-blind, randomised, parallel-group study designed to evaluate the efficacy and safety of dose reduction to tofacitinib 5 mg twice daily (BID) vs remaining on 10 mg BID in patients (pts) with UC in stable remission on tofacitinib 10 mg BID maintenance therapy. Eligible pts had received tofacitinib 10 mg BID for ≥2 consecutive years in an open-label, long-term extension study (NCT01470612), and had been in stable remission for ≥6 months and corticosteroid-free for ≥4 weeks prior to enrolment.1 We aimed to determine if faecal calprotectin (FCP), C-reactive protein (CRP) or partial Mayo score (PMS) can be used as predictors of maintaining remission after dose reduction. Methods Median FCP levels, median CRP levels and mean PMS at baseline (BL), Month 1 and Month 3 were analysed by efficacy endpoint status at Month 6 in pts who dose-reduced to tofacitinib 5 mg BID. The proportions of pts who achieved efficacy endpoints at Month 6 were analysed by stool frequency (SF) subscore, rectal bleeding (RB) subscore and modified PMS. Results Seventy pts were randomised to receive tofacitinib 5 mg BID in RIVETING. For pts in modified Mayo score remission at Month 6, PMS was relatively stable over time, whereas PMS increased from BL to Month 1 and Month 3 in pts not in modified Mayo score remission at Month 6; mean change from BL at Month 3 was 0.1 vs 0.7, respectively (Table 1). This trend was also observed for other efficacy endpoints (Table 1). Median FCP levels did not change from BL to Month 3 in pts who achieved Month 6 efficacy endpoints, whereas median FCP levels increased from BL to Month 3 in pts who did not achieve Month 6 efficacy endpoints (except remission) (Table 1). For all efficacy endpoints, no trend was observed in median CRP levels over time in pts who did and did not achieve Month 6 efficacy endpoints (Table 1). A numerically higher proportion of pts with a SF subscore, RB subscore or modified PMS of 0 at Month 1 or Month 3 achieved efficacy endpoints at Month 6 compared with pts with respective subscores >0 (Table 2). Conclusion These analyses suggest that in pts previously in stable remission, an increase in FCP levels at Month 3, or PMS as early as Month 1, may help predict loss of efficacy after dose-reduction from tofacitinib 10 mg BID to 5 mg BID. A SF subscore, RB subscore or modified PMS of 0 at either Month 1 or Month 3 could indicate the likelihood of maintaining efficacy with tofacitinib 5 mg BID at Month 6. These analyses are post hoc, exploratory and limited by the small sample size. Reference

scholarly journals DOP61 Impact of prior tumour necrosis factor inhibitor failure and prior corticosteroid use on the maintenance of efficacy of tofacitinib following dose reduction in patients with Ulcerative Colitis who were in stable remission: 6-month data from the double-blind, randomised RIVETING study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S096-S097
Author(s):  
W J Sandborn ◽  
M C Dubinsky ◽  
J Torres ◽  
S Vermeire ◽  
P G Kotze ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dose Reduction ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Small Sample Size ◽  
Small Sample ◽  
Double Blind ◽  
Mayo Score ◽  
Induction Study ◽  
Necrosis Factor

Abstract Background Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). RIVETING (NCT03281304) is an ongoing, double-blind, randomised, parallel-group study designed to evaluate the efficacy and safety of dose reduction to tofacitinib 5 mg twice daily (BID) vs remaining on 10 mg BID in patients (pts) with UC in stable remission on tofacitinib 10 mg BID maintenance therapy. Eligible pts had received tofacitinib 10 mg BID for ≥2 consecutive years in an open-label, long-term extension (OLE) study (NCT01470612), and had been in stable remission for ≥6 months (M) and corticosteroid (CS)-free for ≥4 weeks prior to enrolment.1 We aimed to evaluate tofacitinib efficacy outcomes by the number of prior tumour necrosis factor inhibitors (TNFi) failed and by prior CS use. Methods We evaluated the efficacy of tofacitinib 5 mg BID at Month 6 of RIVETING, based on the number of prior TNFi failed (0, 1 or >1), CS use (yes/no) and CS dose (<15 mg/day and ≥15 mg/day) at baseline (BL) of OCTAVE Induction 1&2 and at OLE study BL. CS were prohibited in RIVETING. Results Of the 70 pts randomised to dose-reduce to tofacitinib 5 mg BID, 43 pts had no prior TNFi failure, 17 pts had previous failure with 1 TNFi and 10 pts had previous failure with >1 TNFi. At Month 6, modified Mayo (mMayo) score remission was maintained in 79.1%, 70.6% and 80.0% of pts who had previous failure with 0, 1 and >1 TNFi, respectively. At Month 6, the change from RIVETING BL total Mayo score, mMayo score, partial Mayo score (PMS) and modified PMS was similar across TNFi subgroups (Table 1). Of pts who enrolled into RIVETING, 26 pts were receiving CS (9 received <15 mg/day and 17 received ≥15 mg/day) at induction study BL, and 7 pts were receiving CS at OLE study BL. At Month 6, rates of mMayo score remission were numerically higher in pts with CS use at induction study BL (84.6%) vs those without CS use (72.7%). The rate of mMayo score remission was numerically higher in pts without CS use (77.8%) vs pts with CS use at OLE BL (71.4%), although pt numbers were very low in the CS-use group. These trends were also observed for other efficacy endpoints (Table 2). The Month 6 change from RIVETING BL mMayo score and total Mayo score was numerically higher in pts with vs pts without CS use at induction BL (0.7 and 1.1 vs 0.6 and 0.9, respectively) and OLE BL (1.0 and 1.3 vs 0.6 and 0.9, respectively) (Table 2). Conclusion In pts who were in stable remission for >6M, efficacy endpoints were maintained following dose reduction to tofacitinib 5 mg BID, regardless of the number of prior TNFi failures or prior CS use. These analyses are post hoc and limited by the small sample size. Reference

scholarly journals A randomised, placebo-controlled study of RIPK1 inhibitor GSK2982772 in patients with active ulcerative colitis

2021 ◽  
Vol 8 (1) ◽  
pp. e000680
Author(s):  
Kathy Weisel ◽  
Nicola Scott ◽  
Scott Berger ◽  
Susanne Wang ◽  
Kurt Brown ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ulcerative Colitis ◽  
Disease Activity ◽  
Controlled Study ◽  
Experimental Medicine ◽  
Open Label ◽  
Double Blind ◽  
Treatment Groups ◽  
To Receive

ObjectiveTumour necrosis factor signalling via the receptor-interacting protein kinase 1 (RIPK1) pathway regulates colonic inflammation suggesting that RIPK1 inhibition may be a potential therapeutic target in ulcerative colitis (UC). This phase IIa, randomised, double-blind experimental medicine study investigated the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of the RIPK1 inhibitor GSK2982772 in patients with active UC.DesignIn part A, prior to a protocol amendment, one patient was randomised to receive GSK2982772 60 mg twice daily for 42 days. After the amendment, patients were randomised 2:1 to receive GSK2982772 60 mg or placebo three times daily for 42 days. In part B, all patients switched to open-label GSK2982772 60 mg three times daily for 42 days. Safety, PK, PD biomarkers, histological disease activity, clinical efficacy and quality of life were assessed at days 43 and 85.ResultsThirty-six patients were randomised (n=12, placebo/open-label GSK2982772; n=24, GSK2982772/open-label GSK2982772). Most adverse events were mild, with headache reported the most frequently across groups (placebo/open-label GSK2982772, n=2 (17%); GSK2982772/open-label GSK2982772, n=8 (33%)). GSK2982772 was well distributed into colonic tissue, with generally higher concentrations in colonic biopsy samples versus plasma. No apparent differences between treatment groups were observed for PD, histological disease activity, clinical disease activity or quality-of-life measures. At screening, all patients had Mayo endoscopic scores of 2 or 3. At day 43, no patients in the placebo/open-label GSK2982772 group achieved Mayo endoscopic scores of 0 or 1 vs 3/24 (13%) for GSK2982772/open-label GSK2982772. At day 85, 1/9 (11%) achieved scores of 0 or one for placebo/open-label GSK2982772 vs 3/22 (14%) for GSK2982772/open-label GSK2982772.ConclusionGSK2982772 was generally well tolerated, with no treatment-related safety concerns identified. However, no significant differences in efficacy were observed between treatment groups, suggesting that GSK2982772 as monotherapy is not a promising treatment for patients with active UC.Trial registration numberNCT02903966.

scholarly journals Outcomes of Tofacitinib Dose Reduction in Patients with Ulcerative Colitis in Stable Remission from the Randomized RIVETING Trial

2020 ◽  
Author(s):  
Séverine Vermeire ◽  
Chinyu Su ◽  
Nervin Lawendy ◽  
Taku Kobayashi ◽  
William J Sandborn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Dose Reduction ◽  
Kinase Inhibitor ◽  
Tumor Necrosis Factor Inhibitor ◽  
Janus Kinase ◽  
Double Blind ◽  
Treatment Groups ◽  
Mayo Score ◽  
The Impact

Abstract Background and Aims Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. We present primary completion analysis from RIVETING, an ongoing, double-blind, randomized, parallel-group trial evaluating efficacy and safety of tofacitinib dose reduction to 5 mg twice daily [BID] versus remaining on 10 mg BID in patients in stable remission on tofacitinib 10 mg BID maintenance therapy. Methods Patients had received tofacitinib 10 mg BID for ≥2 consecutive years and been in stable remission for ≥6 months before enrollment. The primary endpoint was modified Mayo score remission at month 6. Safety was assessed up to February 20, 2020 [data cut-off]. Results 140 patients were randomized [1:1] to tofacitinib 5 or 10 mg BID; 77.1% and 90.0% of patients in the 5 and 10 mg BID groups, respectively, were in modified Mayo score remission at month 6 [adjusted difference 12.9%; 95% CI 0.5–25.0]. Smaller differences between treatment groups were seen in patients with baseline endoscopic subscore of 0 versus 1 [9.8%; –3.0–22.6 and 21.1%; –6.1–48.2, respectively], and in patients without versus with prior tumor necrosis factor inhibitor [TNFi] failure [9.5%; –6.6–25.6 and 17.4%; –1.6–36.3, respectively]. AE and serious AE rates were similar across treatment groups; no deaths were reported. Conclusions Most patients in stable remission on 10 mg BID maintenance therapy maintained remission following dose de-escalation. For patients who dose de-escalated, those in deep endoscopic remission and those without prior TNFi failure were more likely to maintain remission. Efficacy data were limited to the first 6-months; a longer duration of follow-up during RIVETING will further characterize the impact of dose reduction on maintenance of remission. Safety findings were consistent with the established safety profile of tofacitinib.

scholarly journals Randomized Double-blind Placebo-controlled Proof-of-concept Trial of Resveratrol for Outpatient Treatment of Mild Coronavirus Disease (COVID-19)

2021 ◽  
Author(s):  
Marvin R. McCreary ◽  
Patrick M. Schnell ◽  
Dale A. Rhoda
Keyword(s):  
Pulmonary Embolism ◽  
Adverse Events ◽  
Small Sample Size ◽  
Primary Outcome Measure ◽  
Small Sample ◽  
Double Blind ◽  
Phase 2 Study ◽  
Clinically Significant ◽  
Low Incidence ◽  
To Receive

Abstract Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N=105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia and pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female) (or their surrogates). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04-3.10), COVID-related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18-1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16-1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06-15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events. A larger trial could determine efficacy.TRIAL REGISTRATIONS: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020

scholarly journals DOP75 Efficacy of tofacitinib dose escalation to 10 mg BID in patients with UC after completing maintenance therapy in remission and losing response: Data from OCTAVE open-label, long-term extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S112-S113 ◽  
Author(s):  
D T Rubin ◽  
M C Dubinsky ◽  
J Panés ◽  
D C Wu ◽  
N Lawendy ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Small Sample Size ◽  
Mucosal Healing ◽  
Small Sample ◽  
Extension Study ◽  
Open Label ◽  
Post Dose ◽  
Mayo Score ◽  
Kaplan Meier

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in patients with moderate to severe UC in three Phase 3 studies.1 Here, we investigated outcomes in a subpopulation of the ongoing, open-label, long-term extension study (OLE) (OCTAVE Open; NCT01470612; May 2019; database not locked), including maintenance of remission patients receiving tofacitinib 5 mg twice daily (BID) who were dose-escalated to 10 mg BID due to flare. Methods Analysis included the maintenance remission–dose-escalation subpopulation: patients who achieved remission at Week 52 in OCTAVE Sustain (tofacitinib 5 or 10 mg BID, or placebo), entered OLE (5 mg BID), but were dose-escalated to 10 mg BID due to flare (based on total Mayo score [MS]; local read endoscopy). Remission: total MS ≤2 with no subscore >1, and rectal bleeding (RB) subscore 0. Dose escalation during OLE was permitted if patients experienced a flare, defined as ≥3 increase from maintenance study baseline total MS and ≥1 increase in RB and endoscopic subscore (ES; unless ES=3 at baseline and remained 3) after ≥8 weeks of treatment in OLE. Kaplan–Meier for estimation of time to dose escalation was assessed in all OLE maintenance remission population relative to OLE baseline. Partial MS remission (≤2 with no subscore >1; no ES) assessed at Months (M)3, 6, 9 and 12 post-dose-escalation; mucosal healing (MH; ES ≤1) and remission assessed at M12 post-dose-escalation. Adverse events (AEs) also assessed. Results Of the 944 patients enrolled in OLE, 162 were in remission at baseline and received tofacitinib 5 mg BID, and 41 were dose-escalated to 10 mg BID due to flare (22 had prior TNFi failure). The cumulative proportion of patients with dose escalation was 4.3%, 10.6%, 12.6% and 13.2% at M3, 6, 9 and 12 of OLE, respectively. Partial MS remission was 75.0% at M3, and partial MS remission, MH and remission were 95.0%, 63.6% and 57.6%, respectively, at M12 post-dose escalation (Table). One case each of serious infection, herpes zoster (non-serious; opportunistic infection) and malignancy were reported (see Table). Conclusion For patients with moderate to severe UC who entered OLE in remission, received tofacitinib 5 mg BID but flared and were dose-escalated to 10 mg BID, response was recaptured for most by M3 post-dose-escalation and remission was recaptured in the majority by M12. Safety in this subpopulation was generally consistent with that observed in the overall tofacitinib UC programme.2 Due to the small sample size and open-label nature, results should be interpreted with caution. References

A randomized, double-blind study comparing corticorelin acetate with dexamethasone in patients with primary malignant glioma who require increased dexamethasone doses to control symptoms of peritumoral brain edema

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2080-2080 ◽  
Author(s):  
W. R. Shapiro ◽  
L. Mechtler ◽  
L. Cher ◽  
H. Wheeler ◽  
V. Hines ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Study Drug ◽  
Similar Efficacy ◽  
Small Sample ◽  
Double Blind Study ◽  
Karnofsky Performance Score ◽  
Double Blind ◽  
Treatment Groups ◽  
Cerebral Tumors ◽  
Peritumoral Brain Edema

2080 Background: Corticorelin acetate (CrA) is a synthetic peptide of corticotropin-releasing factor, undergoing clinical trials as a treatment for peritumoral edema in patients with cerebral tumors. This study compared CrA therapy vs an increase in dexamethasone (dex) dose (+4 mg) for controlling symptoms in primary glioma patients with a subacute exacerbation. Methods: In addition to their prestudy dex dose, patients were randomized to receive CrA 1 mg bid SC or control (+4 mg dex PO) for 8 weeks. Patients were evaluated at baseline and during weeks 1 and 2 for their neurologic status, Karnofsky Performance Score (KPS), and continuing dex requirements. The primary endpoint was response, defined as no post-baseline increase in dex dose >4 mg for >1 day; stable or improved KPS; and ≥25% improvement in 10-item Neurological Examination Score during weeks 1 and 2. Dex therapy requirements were also evaluated. The study aimed to enroll 120 patients, but was terminated with only 37 patients (20 CrA, 17 control) due to slow recruitment. Results: Formal statistical analyses were not undertaken due to the small sample size. The treatment groups had similar demographic and baseline disease characteristics. Despite the small numbers, the data suggest that CrA treatment had similar efficacy to increased dex: (1) The proportions of responders were similar (CrA 3/20; control 3/17); (2) Comparable proportions of patients completed 8 weeks’ treatment (CrA 16/20; control 12/17); (3) After randomization of blinded study drug (CrA or dex 4 mg), dex dosing remained stable for most patients in each arm (CrA 12/20; control 11/17); (4) The mean daily dex dose was 3 mg in the CrA arm and 7 mg in the control arm. There was a lower incidence of cushingoid symptoms in the CrA arm (CrA 1/20, control 3/17). Patients in the CrA arm reported more injection site erythema and flushing vs. the control arm. CrA was well tolerated and no patient withdrew from the trial because of CrA side effects. Conclusions: CrA may be of value in managing patients with cerebral tumors who have subacute exacerbations of their symptoms, without needing to increase their dex dose. [Table: see text]

Memantine in the Treatment of Executive Function Deficits in Adults With ADHD

2016 ◽  
Vol 21 (4) ◽  
pp. 343-352 ◽  
Author(s):  
Joseph Biederman ◽  
Ronna Fried ◽  
Laura Tarko ◽  
Craig Surman ◽  
Thomas Spencer ◽  
...  
Keyword(s):  
Executive Function ◽  
Stimulant Medication ◽  
Small Sample Size ◽  
Neuropsychological Test ◽  
Small Sample ◽  
Open Label ◽  
Double Blind ◽  
Adjunct Treatment ◽  
Behavior Rating Inventory ◽  
Executive Function Deficits

Objective: To evaluate the efficacy and safety of memantine hydrochloride as an adjunct to stimulant pharmacotherapy for treating executive function deficits (EFDs) in adults with ADHD. Method: This was a 12-week, double-blind, placebo-controlled, randomized clinical trial of memantine added to open-label treatment with stimulant medication. Because of the small sample size, we considered a standardized mean difference (equivalent to effect size) of ≥0.5 and odds ratios ≥2 as indicators of trend improvements. Results: Twelve participants received memantine and 14 received a placebo. Trend improvements favoring memantine were observed on Behavior Rating Inventory of Executive Functions–Adult Inhibition and Self-Monitor subscales when compared with Placebo. No significant changes were noted on the Cambridge Neuropsychological Test Automated Battery. Conclusion: Among adults with ADHD and EFDs, adjunct treatment with memantine to osmotic release oral system-methylphenidate (OROS-MPH) was associated with improvements in selective areas of executive functioning, supporting the need for further research.

scholarly journals OP04 Safety analysis of filgotinib for Ulcerative Colitis: Results from the phase 2b/3 SELECTION study and phase 3 SELECTIONLTE long-term extension study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S004-S006
Author(s):  
S W Schreiber ◽  
M Watanabe ◽  
C Yun ◽  
Y Zhou ◽  
S Zhao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Opportunistic Infections ◽  
Incidence Rates ◽  
Janus Kinase ◽  
Open Label ◽  
Biologic Treatment ◽  
Double Blind ◽  
Treatment Groups ◽  
Maintenance Study

Abstract Background Filgotinib (FIL) is an oral preferential Janus kinase (JAK) 1 inhibitor in development for the treatment of inflammatory diseases. FIL for the treatment of moderately to severely active ulcerative colitis (UC) was evaluated in the phase 2b/3, double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522) and its long-term extension (LTE) study (NCT02914535). Here we report safety results from the FIL UC program. Methods Patients received FIL 100 mg, FIL 200 mg or PBO (2:2:1) once daily orally for up to 11 weeks for induction (cohort 1). At week 11, FIL induction responders were rerandomized 2:1 to continue FIL or receive PBO maintenance for 47 weeks (cohort 2). Week 10 non-responders and patients with worsening disease during the maintenance study were eligible for open-label FIL in the LTE. Patients completing the maintenance study could continue blinded dosing in the LTE. Cohort 3 comprised cohorts 1 and 2 and the LTE. Exposure-adjusted incidence rates (EAIRs) and exposure-adjusted event rates (EAERs) per 100 patient-years (PYs) were calculated for treatment-emergent adverse events (AEs) by treatment group in cohorts 1 and 2 (EAIR) and cohort 3 (EAER). Results In cohort 1, 1069 patients received FIL and 279 patients received PBO; baseline characteristics were generally similar across treatment groups (overall mean age, 43 years; mean UC duration, 8.4 years; mean Mayo Clinic Score, 9.0). EAIRs for AEs of interest were similar across treatment groups in cohorts 1 and 2 (Table 1). Treatment exposure for PBO, FIL 100 mg or FIL 200 mg in cohort 3 (i.e. cohorts 1 + 2 + the LTE) was 318, 360 and 1207 PYs, and median treatment duration was 12, 11 and 67 weeks, respectively. One case of pulmonary embolism occurred with FIL 200 mg induction and three venous thrombosis cases occurred with PBO maintenance/LTE (cohort 3) (Table 2). EAERs for all infections were similar across treatment groups, the most common being nasopharyngitis (Table 2). Opportunistic infections were rare. EAERs for serious infections were low across treatment groups (2.2 [PBO], 3.5 [FIL 100 mg], 2.2 [FIL 200 mg]), the most common being appendicitis (Table 2). EAERs for herpes zoster (HZ) were low in all treatment groups (0.3 [PBO], 0.3 [FIL 100 mg], 1.8 [FIL 200 mg]) (Table 2). HZ infections were cutaneous only and only one was serious. EAIRs for all infections in cohorts 1 and 2 were generally numerically higher for both PBO and FIL in patients over (vs under) 65 years old and in those with (vs without) biologic treatment failure (Figure 1). Conclusion FIL was well tolerated in patients with UC. Aggregation of AEs typical for pan-JAK inhibition was not observed, consistent with preferential JAK-1 inhibition with FIL.

scholarly journals P722 Upadacitinib was not associated with anaemia in patients with moderately to severely active ulcerative colitis: Results from the U-ACHIEVE study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S580-S582
Author(s):  
G D’Haens ◽  
X Hebuterne ◽  
P D R Higgins ◽  
E V Loftus- ◽  
W Zhou ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Janus Kinase ◽  
Double Blind ◽  
Once Daily ◽  
Treatment Groups ◽  
The Common ◽  
Grade 3 ◽  
To Receive ◽  
Dose Dependent

Abstract Background Anaemia is a frequent complication in patients with Crohn’s disease and ulcerative colitis (UC), and patients who respond to treatment generally show improvement in anaemia. Decrease in haemoglobin (Hgb) levels and anaemia may be associated with Janus kinase (JAK) inhibitors. Upadacitinib (UPA), an oral JAK1 selective inhibitor, has demonstrated favourable dose-dependent efficacy in patients with moderately to severely active UC.1 This analysis of data from the U-ACHIEVE study addressed effects of UPA treatment on Hgb levels in patients with UC. Methods U-ACHIEVE (NCT02819635) was a randomised, double-blind, placebo (PBO)-controlled phase 2b clinical trial. Adults with moderately to severely active UC were randomised to receive 7.5, 15, 30, or 45 mg UPA or PBO once daily (QD) for 8 weeks. Hgb levels were measured for all groups at baseline (BL) and weeks 2, 4, 6, and 8. Mean change from BL was calculated for each group. p-values for comparison between UPA and PBO groups were calculated using one-way ANOVA; no multiplicity adjustment was applied. Percentage of patients with Hgb values grade 2 (15–20 g/l Hgb decrease from BL), grade 3 (<80 g/l Hgb level or 21–29 g/l Hgb decrease from BL), and grade 4 (<70 g/l Hgb level or >29 g/l Hgb decrease BL) anaemia were determined for all treatment groups using the Common Terminology Criteria for Adverse Events version 5. Adverse events (AE) were reported by investigators. Results Included in the analysis were 250 patients (mean age ± SD, 42.3 ± 14.2 years; disease duration, 8.2 ± 2.5 years). At BL, most treatment groups had similar mean Hgb levels, except for the 15 mg UPA group, which had significantly lower Hgb levels vs. PBO group (Table). Increased or stable mean levels of Hgb at week 8 vs. BL were observed in most UPA treatment groups. The PBO group had the greatest decrease in Hgb vs. BL at week 8 compared with UPA treatment groups (Figure). Grade ≥2 anaemia was reported in 17.4% of patients receiving PBO and 14.4% of all patients receiving UPA (14.9%, 12.2%, 12.0%, and 17.9% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). Grade ≥3 anaemia was reported in 8.7% of patients receiving PBO and 5% of all patients receiving UPA (6.4%, 6.1%, 6.0%, and 1.8% of patients receiving 7.5, 15, 30, and 45 mg UPA, respectively). One subject receiving 7.5 mg QD UPA had grade 4 anaemia. AE of anaemia was reported in 6.5% of patients receiving PBO and in 2.1%, 8.2%, and 3.8% of patients receiving 7.5, 15, and 30 mg UPA, respectively, but not in the 45 mg UPA group. Conclusion Decreased Hgb levels over time were observed more frequently in the PBO group. The maintenance of Hgb levels in patients receiving UPA was likely because of improvement of underlying UC. Reference

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