scholarly journals P544 Comparison of the efficacy of a second intravenous or subcutaneous anti-TNF in the treatment of ulcerative colitis: Real-world data from the ENEIDA registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S463-S464
Author(s):  
P Torres-Rodriguez ◽  
F Cañete ◽  
M Calafat ◽  
R Sánchez-Aldehuelo ◽  
M Rivero ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Dose Escalation ◽  
Biological Agents ◽  
Lower Probability ◽  
Clinical Activity ◽  
Real World Data ◽  
Loss Of Response ◽  
Remission Rates ◽  
Epidemiological Characteristics

Abstract Background Three anti-TNFs (one intravenous and two subcutaneous) are licensed for the treatment of ulcerative colitis (UC). However, it is not known if the efficacy of a second anti-TNF changes on whether it is intravenous or subcutaneous; this could justify the indication of biological agents with a different mechanism of action in second line. The aim of this study was to compare the efficacy of a second subcutaneous or intravenous anti-TNF in UC. Methods Patients from the prospectively maintained ENEIDA registry treated with consecutively intravenous and subcutaneous anti-TNF, who were naïve to biological agents, were identified. Patients were classified according to the administration route of the first anti-TNF in: IVi (intravenous initially) or SCi (subcutaneous initially). Patients treated for extraintestinal manifestations or pouchitis were excluded. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS) at baseline, 14 and 52 weeks. Loss of response, dose-escalation and treatment discontinuation were also assessed. Results 372 UC patients were included (270 IVi and 102 SCi). Both cohorts were similar in clinical-epidemiological characteristics, except for a higher proportion of patients with moderate-to-severe clinical activity at the beginning of the first anti-TNF in the IVi group (82% vs. 71%; p = 0.017) and at the beginning of the second anti-TNF (62% vs. 74%; p = 0.04). Clinical response and remission rates at week 14 for the second anti-TNF were 41% and 29% in IVi vs. 47% and 25% in SCi, respectively (p = ns). At week 52, clinical response/remission rates of the second anti-TNF were 37%/32% in IVi vs. 40%/29% in SCi (p = ns). A higher response rate at 14 weeks with the second anti-TNF was detected in the SCi group (40% vs. 68%; p = 0.012) when the reason for withdrawal of the first anti-TNF was secondary loss of response. The cumulative persistence of the second anti-TNF treatment in IVi and SCi were 55% and 54% after 1 year, and 41% and 40% after 2 years, respectively (p = ns). The SCi group had lower rates of dose-escalation with the second anti-TNF than IVi (34% and 29% in SCi vs. 57% and 49% in EVi, at 12 and 24 months, respectively -p = 0.004-). Dose-escalation of the first anti-TNF and moderate-to-severe clinical activity at the beginning of the second anti-TNF were associated with a lower probability of remission with the second anti-TNF in the short- and long-term. Conclusion The efficacy of infliximab after failure/intolerance of a subcutaneous anti-TNF is similar to that of subcutaneous anti-TNFs after infliximab failure/intolerance.

scholarly journals Machine learning using clinical data at baseline predicts the efficacy of vedolizumab at week 22 in patients with ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Miyoshi ◽  
Tsubasa Maeda ◽  
Katsuyoshi Matsuoka ◽  
Daisuke Saito ◽  
Sawako Miyoshi ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ulcerative Colitis ◽  
Prediction Model ◽  
Clinical Features ◽  
Unmet Need ◽  
Patient Treatment ◽  
Clinical Activity ◽  
Prediction Tool ◽  
Real World Data ◽  
Predictive Values

AbstractPredicting the response of patients with ulcerative colitis (UC) to a biologic such as vedolizumab (VDZ) before administration is an unmet need for optimizing individual patient treatment. We hypothesized that the machine-learning approach with daily clinical information can be a new, promising strategy for developing a drug-efficacy prediction tool. Random forest with grid search and cross-validation was employed in Cohort 1 to determine the contribution of clinical features at baseline (week 0) to steroid-free clinical remission (SFCR) with VDZ at week 22. Among 49 clinical features including sex, age, height, body weight, BMI, disease duration/phenotype, treatment history, clinical activity, endoscopic activity, and blood test items, the top eight features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were selected for logistic regression to develop a prediction model for SFCR at week 22. In the validation using the external Cohort 2, the positive and negative predictive values of the prediction model were 54.5% and 92.3%, respectively. The prediction tool appeared useful for identifying patients with UC who would not achieve SFCR at week 22 during VDZ therapy. This study provides a proof-of-concept that machine learning using real-world data could permit personalized treatment for UC.

scholarly journals P600 Vedolizumab dose optimisation: Findings from a Belgian registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S501-S502
Author(s):  
E Louis ◽  
V Muls ◽  
P Bossuyt ◽  
A Colard ◽  
A Nakad ◽  
...  
Keyword(s):  
Clinical Response ◽  
Median Duration ◽  
Real World ◽  
Clinical Remission ◽  
Outcome Data ◽  
Real World Data ◽  
Secondary Loss ◽  
Loss Of Response ◽  
Starting Point ◽  
Dose Optimisation

Abstract Background Vedolizumab (VDZ) dose optimisation (DO), by interval shortening from 8-weekly (Q8W) to 4-weekly (Q4W) dosing, is used for patients with secondary loss of response. This report presents outcome data on patients receiving DO in real-world clinical practice in Belgium. Methods The Belgian VDZ Registry (ENcePP EUPAS6469) enrolled 202 VDZ-treated ulcerative colitis (UC) or Crohn’s disease (CD) adult patients (26% with no prior use of anti-TNF therapy) from 19 centres. The median length of VDZ therapy prior to enrolment was 11 months. Patients were followed-up every 6 months with the assessment of IBD features, use of biologics, and disease activity. Clinical remission was defined as Harvey–Bradshaw Index (HBI) <5 or partial Mayo Score (pMS) <2, and clinical response as a 2+ point improvement in pMS or a 3+ improvement in HBI. Results During a median follow-up of 19 months from enrolment, 57 (28%) patients (41 CD and 16 UC) received VDZ Q4W due to secondary loss of response. Q4W was mostly used in patients with CD or with prior anti-TNF therapy failure. The median starting point for Q4W dosing was 16 months after the start of VDZ (interquartile range (IQR) 8–27 months) and median duration of Q4W dosing was 4 months (IQR 2–8 months). After changing to Q4W dosing 44% achieved clinical remission, 3% clinical response, and 53% showed no improvement (Table 1). Among the 17 patients with clinical remission/response on Q4W dosing, 53% de-escalated back to Q8W, and continued with Q8W for a median duration of 12 months, 23.5% remained on Q4W with clinical remission, and 23.5% eventually stopped VDZ due to loss of response. A limitation of this study is that it did not systematically collect data on DO prior to recruitment, hence the proportion of patients receiving DO may be higher than reported here. Conclusion These real-world data show DO plays an important role in management of UC and CD. In this study, 28% of patients received DO following the secondary loss of response to Q8W therapy. Forty-seven per cent of patients receiving Q4W subsequently returned to clinical remission or had a clinical response, and half of these patients successfully returned to Q8W VDZ therapy. Controlled studies are warranted, ideally blinded, using more objective endpoint to reveal the true success rate of dose-optimisation.

scholarly journals P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S545-S546
Author(s):  
M Rutka ◽  
K Farkas ◽  
D Pigniczki ◽  
K Szántó ◽  
B Anita ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Response ◽  
Induction Therapy ◽  
Dose Escalation ◽  
Real Life ◽  
Janus Kinase ◽  
Inadequate Response ◽  
Mayo Score ◽  
Number Of Patients

Abstract Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

scholarly journals P476 Effectiveness and safety of ustekinumab in ulcerative colitis: Real-world evidence from the ENEIDA registry

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S465-S466
Author(s):  
M Chaparro ◽  
A Garre ◽  
M Iborra ◽  
M Sierra ◽  
M Barreiro-de Acosta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Elevated Serum ◽  
Real Life ◽  
Development Program ◽  
Lower Probability ◽  
Clinical Activity ◽  
Mayo Score

Abstract Background The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. Aims Primary: to evaluate the durability of ustekinumab treatment in UC patients in clinical practice. Secondary: to assess the short-term response (at week 16) and the long-term effectiveness (at maximum follow-up) and to assess the safety of ustekinumab in clinical practice. Methods Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Results 95 patients were included (table 1). At week 16, 53% of patients had clinical response (including 35% of patients in remission) (figure 1). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with clinical remission. Long-term remission is represented in figure 2. 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72 (figure 3); primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusion Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

scholarly journals P434 Effectiveness and safety of ustekinumab in ulcerative colitis: real-world evidence from Eneida Registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S394-S395
Author(s):  
M Chaparro ◽  
A Garre ◽  
M Iborra ◽  
M Barreiro-de Acosta ◽  
M J Casanova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real Life ◽  
Development Program ◽  
Analysis Data ◽  
Lower Probability ◽  
Clinical Activity ◽  
Short Term ◽  
Mayo Score ◽  
Patient Status ◽  
Probability Of Response

Abstract Background Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring. Results Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to >2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant). Conclusion Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.

scholarly journals Real-world effectiveness of vedolizumab in inflammatory bowel disease: week 52 results from the Swedish prospective multicentre SVEAH study

2021 ◽  
Vol 14 ◽  
pp. 175628482110233
Author(s):  
Carl Eriksson ◽  
Sara Rundquist ◽  
Vyron Lykiardopoulos ◽  
Ruzan Udumyan ◽  
Per Karlén ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Real World ◽  
Bowel Disease ◽  
Clinical Remission ◽  
Real World Data ◽  
Inflammatory Bowel

Background: Prospectively and systematically collected real-world data on vedolizumab are scarce. We aimed to assess the long-term clinical effectiveness of vedolizumab in inflammatory bowel disease (IBD). Methods: This study was a prospective, observational, multicentre study. Overall, 286 patients with active IBD were included (Crohn’s disease, n = 169; ulcerative colitis, n = 117). The primary outcomes were clinical response at week 12 and clinical remission at week 52, based on the Harvey Bradshaw Index and the partial Mayo Clinic score. Secondary outcomes included clinical remission at week 12, clinical response at week 52, corticosteroid-free clinical remission at week 52, changes in biochemical measures, and health-related quality of life (HRQoL). Results: At baseline, 88% of the patients were exposed to anti-TNF and 41% of the patients with Crohn’s disease had undergone ⩾1 surgical resection. At week 12, clinical response was 27% and remission 47% in Crohn’s disease; corresponding figures in ulcerative colitis were 52% and 34%. Clinical response, remission and corticosteroid-free remission at week 52 were 22%, 41% and 40% in Crohn’s disease and 49%, 47% and 46% in ulcerative colitis, respectively. A statistically significant decrease in median faecal-calprotectin and C-reactive protein was observed at 12 and 52 weeks in patients with Crohn’s disease and ulcerative colitis. The HRQoL measures Short Health Scale and EuroQol 5-Dimensions improved in both Crohn’s disease and ulcerative colitis patients ( p < 0.001). Clinical disease activity at baseline was inversely associated with clinical remission at week 52. Conclusion: Vedolizumab proved effective for the treatment of refractory IBD in clinical practice.

Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis

2015 ◽  
Vol 60 (10) ◽  
pp. 3075-3084 ◽  
Author(s):  
Carlos Taxonera ◽  
Manuel Barreiro-de Acosta ◽  
Marta Calvo ◽  
Cristina Saro ◽  
Guillermo Bastida ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dose Escalation ◽  
Effective Strategy ◽  
Secondary Loss ◽  
Loss Of Response

Evidence of Clinical Activity in a Phase 1 Study of CAL-101, An Oral P110Δ Isoform-Selective Inhibitor of Phosphatidylinositol 3-Kinase, in Patients with Relapsed or Refractory B-Cell Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 922-922 ◽  
Author(s):  
Ian W Flinn ◽  
John C. Byrd ◽  
Richard R Furman ◽  
Jennifer R Brown ◽  
Don M Benson ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Response ◽  
Dose Escalation ◽  
Phase 1 ◽  
Clinical Activity ◽  
B Cell Malignancies ◽  
Phase 1 Study ◽  
Drug Concentrations ◽  
Dose Levels ◽  
Phosphatidylinositol 3

Abstract Abstract 922 Introduction: The class I phosphatidylinositol 3-kinases (PI3Ks) regulate a variety of cellular functions relevant to oncogenesis, including metabolism, proliferation and survival. The PI3K p110Δ isoform is primarily expressed in cells of hematopoietic origin and plays a key role in normal B cell maturation and function. CAL-101 is an oral, potent inhibitor of PI3K p110Δ (IC50 of 2.5 nM against purified enzyme and EC50 of 65 nM in a whole blood basophil assay) with 40 to 300-fold selectivity compared to other PI3K isoforms. This selectivity may provide a better therapeutic index relative to pan-PI3K inhibitors. In vitro studies of 0.1 to 10 uM CAL-101 showed inhibition of AKT phosphorylation and/or apoptotic effects against primary chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) cells and against a range of leukemia, lymphoma and multiple myeloma (MM) cell lines. Methods and Patients: A Phase 1 study was undertaken to evaluate the safety and clinical activity of CAL-101 in patients with select hematologic malignancies. During initial dose escalation, sequential cohorts of 3 patients with relapsed/refractory CLL or select B-cell non-Hodgkin's lymphoma (NHL) were enrolled to determine dose limiting toxicity (DLT). During subsequent cohort expansion, approximately 12 patients each with CLL, indolent NHL, aggressive NHL, and AML were to be enrolled. CAL-101 was administered orally twice daily (BID) continuously for 28 days per cycle. Clinical response was evaluated at the end of Cycles 1 and 2 and every 2 cycles thereafter. Results: To date, 43 patients have been enrolled and followed for at least 4 weeks, consisting of 17 patients with CLL, 9 patients with indolent NHL, 10 patients with aggressive NHL and 7 patients with AML. The demographic and disease characteristics were 33% female, mean age 65 (60% over age 65), 49% had refractory disease and the median number of prior regimens was 5. During dose escalation (n=12), 3 patients per cohort were administered dose levels of 50 mg, 100 mg, 200 mg or 350 mg BID. In cohort expansion 31 patients were enrolled to either 200 mg (n=17) or 350 mg (n=14) BID. The median duration of treatment at data cutoff was 3 cycles (range 1 to 10). Two patients discontinued early due to adverse events, one for acute on chronic renal failure and one for abnormal liver function tests (LFTs). DLTs were observed in 5 patients with increases in LFTs, which resolved following discontinuation of CAL-101 dosing. No patient had Grade 4 hematological toxicity. Serious infections were reported in 9 patients, with pneumonia being the most frequent. 41 patients were evaluable for clinical response. At data cutoff, the response rate in NHL was 10/18 (56%); all were partial responses (PR). Of the 9 patients with indolent NHL, 5 patients had PR and 2 patients had stable disease (SD) and remained on study. Of the 9 patients with aggressive NHL, 5 patients had PR (all with mantle cell lymphoma) and 1 patient had SD on study. Of the 17 patients with CLL, 6 patients had PR and 7 other patients had >50% reduction in lymphadenopathy and concurrent increase in peripheral blood lymphocytosis to >50% of baseline, suggesting compartmentalization shift of CLL cells. Lymphocytosis was maximal during the first 2 cycles and decreased thereafter. This effect of dislocating CLL cells from the tissue microenvironment suggests that CAL-101 treatment in combination with cytotoxic agents may be particularly active. Of the 6 patients with AML, no patient had responded and 2 patients remained on study. Clinical responses were observed in patients at all 4 dose levels administered. At data cutoff, the longest duration of response was 9 months in a patient with follicular lymphoma, which was longer than the response to any of the 6 prior regimens this patient received, including autologous hematopoietic stem cell transplant. Plasma exposure increased from 50 mg to 200 mg, without further change at 350 mg. At the 200 mg and 350 mg dose levels, mean peak and trough drug concentrations at the end of Cycle 1 were 5 uM and 1 uM, respectively. Enrollment in cohort expansion is continuing with the addition of patients with MM and updated data will be presented at the meeting. Conclusions: Interim results from the first Phase 1 study to evaluate an oral PI3K p110Δ inhibitor, CAL-101, show promising activity in patients with relapsed or refractory B-cell malignancies with acceptable toxicity. Disclosures: Byrd: Calistoga Pharmaceuticals, Inc: Consultant. Furman:Calistoga Pharmaceuticals, Inc: Consultant. Brown:Calistoga Pharmaceuticals, Inc: Consultant. Giese:Calistoga Pharmaceuticals, Inc: Employment, Ownership Interest. Yu:Calistoga Pharmaceuticals, Inc.: Employment, Ownership interest.

scholarly journals P510 Dose escalation of subcutaneous vedolizumab in patients with ulcerative colitis: A post hoc analysis of the VISIBLE trial data

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S442-S443
Author(s):  
W Sandborn ◽  
D Wolf ◽  
G D’haens ◽  
J Jansson ◽  
J Chen ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Treatment Failure ◽  
Clinical Response ◽  
Dose Escalation ◽  
Clinical Remission ◽  
Severe Disease ◽  
Response Rates ◽  
Response To Treatment ◽  
Dosing Regimen ◽  
Open Label

Abstract Background Vedolizumab (VDZ), a gut-selective, α 4β7 integrin monoclonal antibody, is approved for intravenous (IV) administration to patients with moderate-severe ulcerative colitis (UC). Subcutaneous (SC) VDZ was evaluated for maintenance therapy for UC in VISIBLE 1, a double-blind, placebo-controlled, Phase 3 study, and its open-label extension (OLE). We evaluated the efficacy of increasing dose frequency of VDZ SC from every-2-weeks (Q2W) to weekly administration (QW) after treatment failure (disease worsening or need for rescue medication). Methods In VISIBLE 1 (NCT02611830; EudraCT 2015-000480-14), a Q2W dosing regimen was used for patients with UC who achieved clinical response at week 6 (after open-label IV VDZ inductions at weeks 0 and 2) and were randomised to maintenance treatment with VDZ SC. Patients who did not respond at week 6 but responded by week 14 rolled over to the VISIBLE OLE (NCT02620046; EudraCT: 2015-000482-31) and received Q2W VDZ SC dosing. In VISIBLE 1 and the OLE, 2 groups of patients experienced dose escalation: (1) patients who entered the VISIBLE OLE study on a Q2W VDZ dosing regimen but experienced disease worsening and were escalated to QW dosing (OLE Q2W/QW); and (2) patients who experienced treatment failure during Q2W VDZ treatment in VISIBLE 1, rolled over to OLE, and were escalated to a QW dosing regimen (VISIBLE 1 treatment failure). Efficacy was evaluated by clinical remission and response rates after dose escalation using partial Mayo scores at the visits in the Visible OLE study. In this interim analysis, not all patients continuing in the trial had not completed all study visits. Only patients who had completed a given visit (evaluable patients) were included in the analyses for that visit. Results Of the 54 patients who received dose escalation 52% were male. Mean age was 39 years, mean UC duration was 7.4 years; 76% had severe disease activity (Mayo 9–12) at baseline, and 43% had prior anti-TNF therapy failure (Table 1). Of the patients with dose escalation, 27.1% (13/48 evaluable patients) recaptured clinical remission 16 weeks after dose escalation and 10.8% (4/37 evaluable patients) were in clinical remission after 48 weeks (Table 2). A similar trend was observed for clinical response rates in this patient population. Conclusion Increasing the frequency of VDZ SC dosing to QW recaptured lost response to treatment for some patients. These are interim results of the OLE study; further follow-up during the ongoing OLE will provide more insight into the long-term efficacy and safety of dose escalation with VDZ SC.

Sign in / Sign up

Export Citation Format

Share Document