scholarly journals DOP86 Corticosteroid-sparing effects of ustekinumab therapy for Ulcerative Colitis through 3 years: UNIFI long-term extension

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S117-S118
Author(s):  
E J Scherl ◽  
D S Rowbotham ◽  
S Danese ◽  
W J Sandborn ◽  
Y Miao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Treatment Failure ◽  
Dose Adjustment ◽  
Corticosteroid Dose ◽  
Dosing Regimens ◽  
Symptomatic Remission ◽  
To Receive ◽  
Maintenance Study

Abstract Background Ustekinumab (UST) is an IL12/23 blocker approved for use in Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate-severe UC, >90% of the pts who achieved clinical response or remission at week (wk) 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 3 years among pts who were treated in the UNIFI long-term extension (LTE). Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, pts in the LTE were eligible to receive dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated in randomized pts using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0). During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk152 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data was managed using last observation carried forward. Results Of the 284 pts in the randomized population who were treated with UST in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 91.4% (n=127) were no longer receiving corticosteroids at wk152. The average prednisone-equivalent corticosteroid dose among pts receiving corticosteroids at maintenance baseline in the q8w group was 15.4 mg/day at maintenance baseline and 1.7 mg/day at wks44 & 152. In the q12w group, average prednisone-equivalent doses were 15.4, 1.0, and 4.6 mg/day, respectively (Table 1). Corticosteroid-free symptomatic remission rates through wk152 are summarized in Table 2. Results were similar for the q8w and q12w maintenance doses. Of the UST-treated pts who were in symptomatic remission at wk152, 94.6% (88/93) in the q12w group and 98.0% (97/99) in the q8w group were corticosteroid-free. Conclusion UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 3 years. Through 3 years of treatment with UST, the majority of pts in symptomatic remission were corticosteroid free.

scholarly journals DOP12 Efficacy of ustekinumab for ulcerative colitis through 2 years: Results of the UNIFI maintenance study and long-term extension

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S049-S049 ◽  
Author(s):  
R Panaccione ◽  
W J Sandborn ◽  
B E Sands ◽  
C Marano ◽  
C D O’Brien ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Treatment Failure ◽  
Dose Adjustment ◽  
Stool Frequency ◽  
Treatment Experience ◽  
Mayo Score ◽  
Symptomatic Remission ◽  
To Receive ◽  
Maintenance Study

Abstract Background Ustekinumab (UST) is a mAb to IL-12/23p40 that is approved for moderate-to-severe ulcerative colitis (UC). The UNIFI maintenance study evaluated SC UST through 1 year in patients who responded to UST IV induction. Patients who completed the maintenance study could enter a long-term extension (LTE) through 220weeks. Here, we report the efficacy of UST through 92weeks for patients randomised in the maintenance study. Methods Patients who were in clinical response 8weeks after UST induction were randomised to SC PBO (n = 175), UST 90mg q12w (n = 172), or UST 90mg q8w (n = 176). All patients who completed Week 44 were eligible to enter and continue in the LTE at the investigator’s discretion. Subsequent to completion of the maintenance study at Week 44, unblinding occurred and patients who were receiving PBO were discontinued from the LTE. During the LTE, patients were eligible to receive dose adjustment (q12w to q8w or q8w to q8w [sham dose adjustment]) starting at Week 56 based on investigator assessment of their UC disease activity. Symptomatic remission (stool frequency subscore of 0 or 1 and rectal bleeding subscore of 0) and partial Mayo remission (partial Mayo score ≤2) were evaluated through Week 92. Analyses of symptomatic remission and partial Mayo over time included all patients randomised in maintenance and were performed separately, with dose adjustment as part of the treatment experience (ie, not a treatment failure) and with adjustment considered as a treatment failure. Results Symptomatic and partial Mayo remission were sustained through Week 92, with no clinically meaningful differences between the q12w and q8w dose groups (Figure 1 and 2). When dose adjustment was considered to be part of the treatment experience (ie, not a treatment failure), 66.1 % and 67.0% of patients randomised to q12w and q8w, respectively, were in symptomatic and partial Mayo remission at Week 92 (Figure 1). When dose adjustment was considered to be a treatment failure in the analysis, 53.2% and 54.0% of patients were in symptomatic and partial Mayo remission, respectively (Figure 2). The safety profile of UST through Week 96 was consistent with that previously reported for 1 year. Conclusion The efficacy of UST in patients with moderate-to-severe UC has maintained through 92weeks with q12w or q8w SC dosing when dose adjustment was considered to be part of the treatment experience.

scholarly journals DOP76 Corticosteroid sparing effects of ustekinumab therapy for ulcerative colitis through 2 years: UNIFI long-term extension

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S113-S114
Author(s):  
L Peyrin-Biroulet ◽  
W Sandborn ◽  
B Sands ◽  
E Scherl ◽  
C Marano ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Treatment Failure ◽  
Clinical Response ◽  
Dose Adjustment ◽  
Intention To Treat ◽  
Remission Rates ◽  
Symptomatic Remission ◽  
To Receive ◽  
Maintenance Study

Abstract Background Ustekinumab (UST) is an IL12/23 blocker approved for Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients with moderate–severe UC, >90% of the patients who achieved clinical response or remission at week 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid (CS) sparing effects of UST treatment through week 92 among patients who were treated in the UNIFI long-term extension (LTE). Methods Responders to UST 8 weeks after IV induction entered the maintenance study and were randomised to UST 90mg SC (q12wks or q8wks) or PBO. Patients who did not respond to UST IV induction received a dose of UST 90mg SC at week 8 and were evaluated at week 16. Those in clinical response at week 16 (delayed responders), were not randomised on entry into the maintenance study and received UST 90mg q8wk. All patients who completed week 44 of the maintenance study were eligible to enter the LTE and continue to receive the same dose. Patients could receive UST dose adjustment during the LTE (q12wk to q8wk or q8wk to q8wk [sham dose adjustment]) from week 56 onward. Patients who remained on PBO were discontinued from the LTE after maintenance study unblinding. During the maintenance study, CS tapering was recommended for all patients receiving CS at maintenance baseline. At week 92 of the LTE, CS-free symptomatic remission rates and CS use were calculated using intention-to-treat analyses with a dose adjustment considered to be a treatment failure and with a dose adjustment not considered to be a treatment failure. Results Of the 284 patients in the randomised population who were treated with UST in the LTE, 139 were receiving CS at maintenance baseline. Of these, 92.8% (n = 129) were CS-free at week 92. CS-free symptomatic remission rates at week 92 are summarised in Table 1. Results were similar for the q8wk and q12wk maintenance doses. Of the UST-treated patients who were in symptomatic remission at week 92, 98.4% (182/185) were CS-free; similar results were seen when dose adjustment was not considered to be a treatment failure. Of the 116 delayed responders (non-randomised population) who continued to receive UST in the LTE, 92 patients were in symptomatic remission at week 92; of whom, 94.6% (87/92) were CS-free. Conclusion UST maintenance therapy, with both q8wk and q12wk dosing regimens, was effective in reducing and eliminating the use of CS in patients with UC. Nearly all patients in the LTE who were in symptomatic remission at week 92, were not taking steroids.

scholarly journals P508 Dose adjustment in patients with moderate to severe ulcerative colitis: results from year 3 of the UNIFI maintenance study long-term extension

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S488-S489
Author(s):  
D S Rowbotham ◽  
E J Scherl ◽  
B E Sands ◽  
R Panaccione ◽  
L Peyrin-Biroulet ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Markers ◽  
Dose Adjustment ◽  
Active Ulcerative Colitis ◽  
Severe Ulcerative Colitis ◽  
Symptomatic Remission ◽  
To Receive ◽  
Adjustment Table ◽  
Maintenance Study

Abstract Background The UNIFI randomized-withdrawal maintenance study and long-term extension (LTE) evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment through Week (Wk) 152 of the long-term extension (LTE). Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 weeks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST patients who completed wk44 entered the LTE. PBO patients were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Wk 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Patients in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Patients were assessed for symptomatic remission, partial Mayo scores, and inflammatory markers ≥16 wks after dose adjustment. Results Overall, 60 patients (42.6%) in the q12w group and 40 patients (28.0%) in the q8w group underwent dose adjustment (or sham dose adjustment) prior to Wk 156 of the LTE; 51 and 39 patients in each group, respectively, had dose adjustment at Wk 136 or before, providing≥16 wks of data after dose adjustment (Table). At the first visit ≥16 weeks after dose adjustment, 70.6% of patients who adjusted from q12w to q8w and 61.5% who sham dose adjusted from q8w to q8w were in symptomatic remission. At the time of dose adjustment, 27/51 patients (52.9%) in the q12w group and 25/39 patients (64.1%) in the q8w group were in symptomatic remission. Of those who were in symptomatic remission at the time of dose adjustment, the majority (81.5% and 68.0%, respectively) were maintained in symptomatic remission at the first visit ≥16 wks after dose adjustment. Of those who were not in symptomatic remission at the time of dose adjustment, 58.3% and 50.0%, respectively, were in symptomatic remission at the first visit ≥16 wks after dose adjustment. Mean partial Mayo scores and CRP levels decreased after dose adjustment (Table). Conclusion Patients may benefit from UST dose adjustment to q8w.

scholarly journals P448 Dose adjustment in patients with moderate-to-severe ulcerative colitis: results from the UNIFI maintenance study long-term extension

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S403-S403 ◽  
Author(s):  
S Danese ◽  
R Panaccione ◽  
L Peyrin-Biroulet ◽  
C Marano ◽  
C D O’Brien ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Safety Profile ◽  
Inflammatory Markers ◽  
Dose Adjustment ◽  
Active Ulcerative Colitis ◽  
Symptomatic Remission ◽  
To Receive ◽  
Adjustment Table ◽  
Maintenance Study

Abstract Background The UNIFI randomised-withdrawal maintenance study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients (patients) with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment during the long-term extension (LTE). Methods At Week (Week) 0 of the 44 weeks maintenance study, 523 patients who had responded to IV UST induction were randomly assigned in a 1:1:1 ratio to placebo (PBO) SC, UST SC 90 mg q12w, or 90 mg q8w. Patients who completed the maintenance study were eligible to enter the LTE if the investigator thought they would benefit from continued treatment. PBO patients were discontinued from the LTE after the maintenance study was unblinded and the analysis was complete. Based on investigator’s clinical judgement of UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Week 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). PBO patients were only eligible for dose adjustment before unblinding. Patients were assessed for symptomatic remission (SR), partial Mayo scores, and inflammatory markers ≥16 weeks after dose adjustment. Results Symptomatic remission was maintained through Week 92 among patients treated with UST regardless of dose adjustment in the LTE (Figure). Overall, 40 (28.4%) and 37 (25.9%) patients in the q12w and q8w groups, respectively, underwent dose adjustment (or sham dose adjustment) prior to Week 92 of the LTE. Among patients who received dose adjustment at Week 76 or before and had data ≥16 weeks after dose adjustment, symptomatic remission was observed in 70.0% in the q12w-to-q8w group and 71.4% in the q8w-to-q8w group, the majority of whom were in symptomatic remission at the time of the dose adjustment (Table). The safety profile of UST in patients who received dose adjustment was generally consistent with the overall safety profile of UST. Conclusion Patients may benefit from UST dose adjustment to q8w. However, the majority of UST-treated patients were in SR at the time of dose adjustment in this study. No new safety signals were observed among patients who dose adjusted.

scholarly journals P712 Association of histologic-endoscopic mucosal healing after ustekinumab induction or maintenance therapy with 2-year outcomes in the UNIFI Phase 3 study in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S574-S575
Author(s):  
K Li ◽  
F Yang ◽  
C Marano ◽  
H Zhang ◽  
W J Sandborn ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Disease Activity ◽  
Clinical Remission ◽  
Dose Adjustment ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
To Receive ◽  
Lower Disease Activity

Abstract Background Ustekinumab (UST) is an effective therapy for moderate-to-severe ulcerative colitis (UC). Histological and endoscopic improvement of mucosa after induction are associated with clinical remission and steroid-free clinical remission at maintenance Week 44. The association of histological-endoscopic mucosal healing after UST induction or maintenance therapy with 2-year outcomes in moderate-to-severe UC is not known. Methods In the UNIFI study of UST in moderate-to-severe UC, histological-endoscopic mucosal healing was defined as achieving both endoscopic improvement (Mayo endoscopy subscore ≤1) and histological improvement (i.e., neutrophil infiltration in <5% of crypts, no crypt destruction, and no erosions, ulcerations, or granulation tissue; based on the Geboes score). Associations of mucosal improvement after induction (irrespective of treatment) or UST maintenance with long-term efficacy of UST, disease severity, inflammation level, and dose adjustment were evaluated up to Week 92 in the long-term extension (LTE) phase of UNIFI. Analysis was conducted in patients who were randomised to receive UST maintenance therapy and continued with UST in LTE. Tests with p-value <0.05 were considered statistically significant. Results Patients with histological-endoscopic mucosal healing after induction had significantly lower disease activity (partial Mayo score and stool frequency) and a trend for lower inflammation measured by CRP and faecal calprotectin at maintenance Week 44 than those without induction mucosal healing (Table 1). These improvements in disease activity were retained through LTE Week 92, with patients with induction histological-endoscopic mucosal healing showing a continuous reduction of disease activity. Significantly lower disease activity, CRP, and faecal calprotectin were also observed through LTE among patients with histological-endoscopic mucosal healing after UST maintenance compared with those without (Table 1). Patients with histological-endoscopic mucosal healing after induction remained on treatment longer than those without (p < 0.05). In addition, patients with histological-endoscopic mucosal healing after induction or maintenance were less likely to receive dose adjustment during LTE, but this association was not statistically significant. Conclusion Early macroscopic and microscopic improvement of the mucosa is an indicator of positive long-term clinical outcomes and reductions in inflammatory burden.

scholarly journals P565 Efficacy and safety of long-term treatment with ustekinumab in moderate–severe ulcerative colitis patients with delayed response to ustekinumab induction: Results from UNIFI 2-year long-term extension

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S476-S477 ◽  
Author(s):  
B E Sands ◽  
M T Abreu ◽  
R W L Leong ◽  
C Marano ◽  
C D O’Brien ◽  
...  
Keyword(s):  
Clinical Response ◽  
Biologic Therapy ◽  
Induction Treatment ◽  
Delayed Response ◽  
Efficacy And Safety ◽  
Long Term Treatment ◽  
Symptomatic Remission ◽  
To Receive ◽  
Maintenance Study

Abstract Background Ustekinumab (UST) has been shown to induce and maintain clinical response and remission in moderate–severe UC patients in the UNIFI study. In the UNIFI maintenance study, the primary randomised population consisted of patients who were in clinical response 8weeks after UST induction treatment. Patients who had a delayed response to induction were also eligible for the maintenance study but were not included in the randomised analysis set. Here, we present the efficacy and safety of UST maintenance among delayed responders who were treated in the UNIFI long-term extension(LTE). Methods UNIFI was a single protocol of induction and randomised withdrawal maintenance studies in patients with moderate–severe UC who failed conventional or biologic therapy(including TNF antagonists and/or vedolizumab). Delayed responders were patients who were not in clinical response to UST IV induction at Week8 but achieved response at Week16 following a single UST90mg SC dose at Week8. These patients entered the maintenance study and continued to receive UST90mg SC q8w. Patients who completed Week44 evaluations were eligible to enter LTE continuing to receive UST90mg SC q8w. Efficacy in delayed responders to UST(who were treated in LTE) was evaluated over time through Week92 and safety through Week96. Results 116 delayed responders to UST induction were treated in the LTE, including 58 who had previously failed biologic therapy and 58 who had not failed biologic therapy, 54 of whom were bio-naïve. Symptomatic remission(defined as stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) rates in delayed responders to UST induction increased from maintenance baseline to Weeks 44 and 92 (Table 1). Similar trends were seen within the biologic failure subgroups; although, rates among patients who had not failed biologics (primarily bio-naïve) were greater than those of patients who had failed biologics. Among the 79.3% (n = 92/116) of delayed responders to UST in symptomatic remission at Week 92, 94.6% (n = 87/92) were corticosteroid free. Safety data for randomised and non-randomised patients treated in UNIFI LTE is in Table2. The safety profile for UST in delayed responders was generally similar to that observed among patients randomised to UST; no new safety signals were observed. Conclusion Delayed responders to UST treatment maintained symptomatic remission through Week 92 with UST90mg SC q8w and the majority did so in the absence of corticosteroids.

Tu1886 DOSE ADJUSTMENT IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS: RESULTS FROM THE UNIFI MAINTENANCE STUDY LONG-TERM EXTENSION

2020 ◽  
Vol 158 (6) ◽  
pp. S-1204
Author(s):  
Bruce E. Sands ◽  
Remo Panaccione ◽  
Laurent Peyrin-Biroulet ◽  
Colleen W. Marano ◽  
Christopher D. O'Brien ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Dose Adjustment ◽  
Severe Ulcerative Colitis ◽  
Maintenance Study

scholarly journals DOP83 Efficacy and Safety of Ustekinumab for Ulcerative Colitis Through 3 Years: UNIFI Long-term Extension

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S113-S115
Author(s):  
M T Abreu ◽  
S Danese ◽  
W J Sandborn ◽  
Y Miao ◽  
I Tikhonov ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Maintenance Therapy ◽  
Opportunistic Infections ◽  
Failure Criteria ◽  
Major Adverse Cardiovascular Events ◽  
Prior History ◽  
Neutropenic Sepsis ◽  
Symptomatic Remission

Abstract Background Ustekinumab (UST) is an IL-12/23p40 antagonist used to treat pts with moderate-to-severe ulcerative colitis (UC). The ongoing UNIFI long-term extension (LTE) evaluates subcutaneous (SC) 90mg UST maintenance therapy, with efficacy (wk152) and safety (wk156) results reported here. Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (175 SC placebo [PBO]; 172 UST 90mg every 12 weeks [q12w]; 176 UST 90mg q8w). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Starting at wk56, randomized pts with UC worsening could adjust to q8w. Symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0) was evaluated in randomized pts. Safety was evaluated for all 588 pts treated in the LTE, including the randomized and nonrandomized populations; 188 received PBO and 457 received UST. The nonrandomized population included responders to PBO induction and UST induction nonresponders at wk8 who received SC UST, responded 8 wks later and received UST 90mg q8w. Results Among all pts randomized to UST at maintenance baseline (intent-to-treat population with nonresponder imputation for missing data and treatment failure criteria), 55.2% were in symptomatic remission at wk152 (biologic naïve, 66.1%; biologic failures, 43.5%; Table 1); 96.4% (185/192) of pts in symptomatic remission at wk152 were corticosteroid-free. Overall, 20.1% (39/149 biologic failure, 16/149 biologic naïve) of pts who were randomized to UST and treated in the LTE discontinued treatment between wks44 and 156. Among randomized pts treated with UST in the LTE, 67.6% were in symptomatic remission at wk152; 76.4% of those in clinical remission at wk44 were in symptomatic remission at wk152; and 84.1% of pts with observed data at wk152 were in symptomatic remission. From maintenance wk0-156, combined UST and PBO pts had 1281.6 and 425.0 pt-years of follow-up, respectively; and safety events per 100 pt-years of follow-up for combined UST vs PBO were AEs: 235.81 vs 204.48, SAEs: 7.73 vs 7.53, and serious infections: 2.34 vs 2.35 (Table 2). From wks96-156, there were no reported deaths or major adverse cardiovascular events. One UST-treated pt with fair skin and a prior history of basal cell carcinoma (BCC) reported 2 BCC. One 90 mg q8w UST pt receiving concomitant 6-MP reported SAEs of neutropenic sepsis and oral herpes SAE; the latter events were considered potential opportunistic infections. The dose of 6-MP was reduced, pt recovered and continued UST. Conclusion The efficacy of UST in pts with UC was sustained through 3 years. No new safety signals were observed.

scholarly journals DOP73 Efficacy and safety of escalation to tofacitinib 10 mg BID for patients with UC following loss of response on 5 mg BID maintenance therapy: Results from OCTAVE open-label, long-term extension study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S110-S111 ◽  
Author(s):  
B E Sands ◽  
A C Moss ◽  
A Armuzzi ◽  
J K Marshall ◽  
J O Lindsay ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Treatment Failure ◽  
Induction Therapy ◽  
Dose Escalation ◽  
Safety Data ◽  
Mucosal Healing ◽  
Incidence Rates ◽  
Efficacy And Safety ◽  
Open Label

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib have been demonstrated in patients with moderate to severe UC in three Phase 3 studies (OCTAVE Induction 1 and 2 [NCT01465763; NCT01458951]; OCTAVE Sustain [NCT01458574]) [1]. Here, we present updated efficacy and safety data of tofacitinib dose escalation in patients with UC participating in an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612) [2]. Methods We present updated data from the dose-escalation subpopulation of the OLE study (as of May 2019; database not locked) comprising patients who achieved clinical response (CR) following 8 weeks of tofacitinib 10 mg twice daily (BID) induction therapy, entered OCTAVE Sustain receiving tofacitinib 5 mg BID, experienced treatment failure between Week 8 and Week 52, and subsequently entered OCTAVE Open with escalation to tofacitinib 10 mg BID. Treatment failure was defined as an increase of ≥3 points from maintenance study baseline total Mayo score, plus an increase of ≥1 point in both rectal bleeding subscore and centrally read endoscopic subscore (ES), and an absolute ES of ≥2 after ≥8 weeks of maintenance therapy. CR, mucosal healing (MH) and remission (R) were evaluated at Months 2, 12, 24 and 36 of OCTAVE Open (non-responder imputation and last observation carried forward [NRI-LOCF] and observed data). Safety was evaluated throughout the study. Results Of 944 patients enrolled in the OLE study, the dose escalation subpopulation comprised 59 patients. In these patients, CR, MH and R rates 36 months after dose escalation were, respectively, 40.7%, 39.0% and 30.5% for NRI-LOCF and 95.2%, 86.4% and 66.7% for observed data (Table). Of these 59 patients, 29 had prior tumour necrosis factor inhibitor (TNFi) failure; in these patients, CR, MH and R rates at Month 36 were, respectively, 51.7%, 51.7% and 41.4% for NRI-LOCF, and 100.0%, 92,3% and 75.0% for observed data. Incidence rates for safety events and pt-years’ exposure are reported in the table. Conclusion For most patients who lost initial CR to tofacitinib 10 mg BID induction therapy while on tofacitinib 5 mg BID maintenance therapy, including those with prior TNFi failure, dose-escalation back to 10 mg BID recaptured CR by Month 2 and was generally maintained over 3 years. The safety profile with tofacitinib 10 mg BID in the dose-escalation subpopulation was generally consistent with that in the overall study population, although there was a numerically higher rate of herpes zoster. These analyses are limited by low pt numbers and the absence of a comparator arm. References

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