https://orcid.org/0000-0003-4622-8441
-
PDF
- Split View
-
Views
-
Cite
Cite
Rahul S Dalal, Rachel W Winter, Sanchit Gupta, Gila F Sasson, Matthew J Hamilton, Jessica R Allegretti, Clinical Outcomes at 8-16 Weeks After Upadacitinib Initiation for Acute Severe Ulcerative Colitis: A Case Series in the United States, Inflammatory Bowel Diseases, Volume 30, Issue 6, June 2024, Pages 1042–1043, https://doi.org/10.1093/ibd/izae038
Close - Share Icon Share
Lay Summary
In 9 patients hospitalized for acute severe ulcerative colitis, 8 were successfully discharged without the need for colectomy. Six of 7 patients with sufficient follow-up achieved steroid-free clinical remission at 8 to 16 weeks, and 1 of 2 patients achieved endoscopic response.
Case Series
There are limited data regarding the effectiveness of upadacitinib for acute severe ulcerative colitis (ASUC).1-3 We described clinical outcomes through 8 to 16 weeks after upadacitinib initiation for ASUC.
Nine patients initiated upadacitinib (45 mg daily) during hospitalization for ASUC at a Brigham and Women’s Hospital (Boston, MA, USA) between January 1, 2023, and December 31, 2023. Seven had prior exposure to antitumor necrosis factor (TNF) agents and 3 received infliximab during hospitalization prior to upadacitinib (Table 1). Two patients had contraindications to anti-TNF therapy. Seven patients had Mayo endoscopic subscores of 3 on index sigmoidoscopy and were clinically refractory to corticosteroids (one patient refused corticosteroids). C-reactive protein improved from day 0 to day 2 after upadacitinib initiation in 5 patients: 244 to 52, 201 to 38, 40 to 7, 19 to 11, and 13 to 8 mg/dL. One patient underwent colectomy 9 days after upadacitinib initation for nonresponse. Median hospital length of stay (LOS) was 11 days, and median LOS after upadacitinib initiation was 5 days.
| Baseline Characteristics . | Value . |
|---|---|
| Female sex, % (n/N) | 67% (6/9) |
| Age at initiation, y, median (IQR) | 33 (25-53) |
| Disease duration, y, median (IQR) | 5 (2-11) |
| White race, % (n/N) | 100% (9/9) |
| Hispanic ethnicity, % (n/N) | 11% (1/9) |
| BMI, median (IQR) | 23 (23-28) |
| Prior infliximab exposure, % (n/N) | 78% (7/9) |
| Prior vedolizumab exposure, % (n/N) | 33% (3/9) |
| Other prior advanced therapy exposures, % (n/N) | 0% (0/9) |
| Index Mayo endoscopic subscore = 3, % (n/N) | 89% (8/9) |
| Days IV steroids until upadacitinib initiation, median (IQR) | 7 (4-11) |
| Serum albumin, g/dL, median (IQR) | 3.4 (3.1-3.6) |
| C-reactive protein, mg/L, median (IQR) | 40 (13-106) |
| Fecal calprotectin, ug/g, median (IQR) | 1369 (1201-2610) |
| SCCAI, median (IQR) | 11 (9-12) |
| Hospitalization Outcomes | Value |
| Hospital LOS, d, median (IQR) | 11 (10-15) |
| LOS after upadacitinib initiation, d, median (IQR) | 5 (2-8) |
| Colectomy, % (n/N) | 11% (1/9) |
| Adverse events, % (n/N) | 11% (1/9: heparin induced thrombocytopenia) |
| Postdischarge Outcomes | Value |
| Corticosteroid-free clinical remission at 8-16 weeks, % (n/N) | 86% (6/7) |
| Clinical response at 8-16 weeks, % (n/N) | 86% (6/7) |
| Endoscopic remission*, % (n/N) | 0% (0/2) |
| Endoscopic response*, % (n/N) | 50% (1/2) |
| Adverse events*, % (n/N) | 11% (1/9: pulmonary embolism) |
| Baseline Characteristics . | Value . |
|---|---|
| Female sex, % (n/N) | 67% (6/9) |
| Age at initiation, y, median (IQR) | 33 (25-53) |
| Disease duration, y, median (IQR) | 5 (2-11) |
| White race, % (n/N) | 100% (9/9) |
| Hispanic ethnicity, % (n/N) | 11% (1/9) |
| BMI, median (IQR) | 23 (23-28) |
| Prior infliximab exposure, % (n/N) | 78% (7/9) |
| Prior vedolizumab exposure, % (n/N) | 33% (3/9) |
| Other prior advanced therapy exposures, % (n/N) | 0% (0/9) |
| Index Mayo endoscopic subscore = 3, % (n/N) | 89% (8/9) |
| Days IV steroids until upadacitinib initiation, median (IQR) | 7 (4-11) |
| Serum albumin, g/dL, median (IQR) | 3.4 (3.1-3.6) |
| C-reactive protein, mg/L, median (IQR) | 40 (13-106) |
| Fecal calprotectin, ug/g, median (IQR) | 1369 (1201-2610) |
| SCCAI, median (IQR) | 11 (9-12) |
| Hospitalization Outcomes | Value |
| Hospital LOS, d, median (IQR) | 11 (10-15) |
| LOS after upadacitinib initiation, d, median (IQR) | 5 (2-8) |
| Colectomy, % (n/N) | 11% (1/9) |
| Adverse events, % (n/N) | 11% (1/9: heparin induced thrombocytopenia) |
| Postdischarge Outcomes | Value |
| Corticosteroid-free clinical remission at 8-16 weeks, % (n/N) | 86% (6/7) |
| Clinical response at 8-16 weeks, % (n/N) | 86% (6/7) |
| Endoscopic remission*, % (n/N) | 0% (0/2) |
| Endoscopic response*, % (n/N) | 50% (1/2) |
| Adverse events*, % (n/N) | 11% (1/9: pulmonary embolism) |
Abbreviations: y, years; d, days; IV, intravenous; IQR, interquartile range; BMI, body mass index; SCCAI, simple clinical colitis activity index; LOS, length of stay.
*These outcomes were assessed during all available follow-up (median 147 days, IQR 38-189 days).
| Baseline Characteristics . | Value . |
|---|---|
| Female sex, % (n/N) | 67% (6/9) |
| Age at initiation, y, median (IQR) | 33 (25-53) |
| Disease duration, y, median (IQR) | 5 (2-11) |
| White race, % (n/N) | 100% (9/9) |
| Hispanic ethnicity, % (n/N) | 11% (1/9) |
| BMI, median (IQR) | 23 (23-28) |
| Prior infliximab exposure, % (n/N) | 78% (7/9) |
| Prior vedolizumab exposure, % (n/N) | 33% (3/9) |
| Other prior advanced therapy exposures, % (n/N) | 0% (0/9) |
| Index Mayo endoscopic subscore = 3, % (n/N) | 89% (8/9) |
| Days IV steroids until upadacitinib initiation, median (IQR) | 7 (4-11) |
| Serum albumin, g/dL, median (IQR) | 3.4 (3.1-3.6) |
| C-reactive protein, mg/L, median (IQR) | 40 (13-106) |
| Fecal calprotectin, ug/g, median (IQR) | 1369 (1201-2610) |
| SCCAI, median (IQR) | 11 (9-12) |
| Hospitalization Outcomes | Value |
| Hospital LOS, d, median (IQR) | 11 (10-15) |
| LOS after upadacitinib initiation, d, median (IQR) | 5 (2-8) |
| Colectomy, % (n/N) | 11% (1/9) |
| Adverse events, % (n/N) | 11% (1/9: heparin induced thrombocytopenia) |
| Postdischarge Outcomes | Value |
| Corticosteroid-free clinical remission at 8-16 weeks, % (n/N) | 86% (6/7) |
| Clinical response at 8-16 weeks, % (n/N) | 86% (6/7) |
| Endoscopic remission*, % (n/N) | 0% (0/2) |
| Endoscopic response*, % (n/N) | 50% (1/2) |
| Adverse events*, % (n/N) | 11% (1/9: pulmonary embolism) |
| Baseline Characteristics . | Value . |
|---|---|
| Female sex, % (n/N) | 67% (6/9) |
| Age at initiation, y, median (IQR) | 33 (25-53) |
| Disease duration, y, median (IQR) | 5 (2-11) |
| White race, % (n/N) | 100% (9/9) |
| Hispanic ethnicity, % (n/N) | 11% (1/9) |
| BMI, median (IQR) | 23 (23-28) |
| Prior infliximab exposure, % (n/N) | 78% (7/9) |
| Prior vedolizumab exposure, % (n/N) | 33% (3/9) |
| Other prior advanced therapy exposures, % (n/N) | 0% (0/9) |
| Index Mayo endoscopic subscore = 3, % (n/N) | 89% (8/9) |
| Days IV steroids until upadacitinib initiation, median (IQR) | 7 (4-11) |
| Serum albumin, g/dL, median (IQR) | 3.4 (3.1-3.6) |
| C-reactive protein, mg/L, median (IQR) | 40 (13-106) |
| Fecal calprotectin, ug/g, median (IQR) | 1369 (1201-2610) |
| SCCAI, median (IQR) | 11 (9-12) |
| Hospitalization Outcomes | Value |
| Hospital LOS, d, median (IQR) | 11 (10-15) |
| LOS after upadacitinib initiation, d, median (IQR) | 5 (2-8) |
| Colectomy, % (n/N) | 11% (1/9) |
| Adverse events, % (n/N) | 11% (1/9: heparin induced thrombocytopenia) |
| Postdischarge Outcomes | Value |
| Corticosteroid-free clinical remission at 8-16 weeks, % (n/N) | 86% (6/7) |
| Clinical response at 8-16 weeks, % (n/N) | 86% (6/7) |
| Endoscopic remission*, % (n/N) | 0% (0/2) |
| Endoscopic response*, % (n/N) | 50% (1/2) |
| Adverse events*, % (n/N) | 11% (1/9: pulmonary embolism) |
Abbreviations: y, years; d, days; IV, intravenous; IQR, interquartile range; BMI, body mass index; SCCAI, simple clinical colitis activity index; LOS, length of stay.
*These outcomes were assessed during all available follow-up (median 147 days, IQR 38-189 days).
Seven patients had postdischarge assessments (the patient who underwent colectomy was considered a treatment failure for postdischarge end points). At the first 8 to 16 week postdischarge appointment, 6 patients remained on upadacitinib and achieved both clinical response (reduction in simple clinical colitis activity index [SCCAI] by ≥3 points) and corticosteroid-free clinical remission (SCCAI ≤2 with no use of oral corticosteroids; Table 1). Five were taking 30 mg daily and one 45 mg daily. Two patients had endoscopic evaluations at 56 and 308 days after upadacitinib initiation, of which the latter patient achieved endoscopic response, but neither achieved endoscopic remission. One adverse event occurred (pulmonary embolism [PE], attributed to heparin induced thrombocytopenia) 47 days after upadacitinib initiation but did not lead to treatment discontinuation. No deaths occurred.
Discussion
This is one of the largest case series to date evaluating the effectiveness of upadacitinib induction for ASUC. Most patients were able to achieve corticosteroid-free clinical remission at 8-16 weeks postdischarge despite having steroid-refractory disease. Upadacitinib appeared to be safe, as only 1 adverse event occurred (PE). While this PE was attributed primarily to heparin-induced thrombocytopenia, the independent risks of deep venous thrombosis with severe UC and Janus-kinase inhibitors should be considered and appropriate prophylaxis administered during hospitalization. When considering the data from this and other published case series, upadacitinib appears to be effective for ASUC. Large prospective studies are needed to confirm these findings and evaluate the long-term safety of upadacitinib in this population.
Author Contributions
R.S.D.: study concept and design, acquisition of data, analysis and interpretation of data, drafting of article
G.F.S., S.C., R.W.W., M.J.H.: acquisition of data, critical revision of the article for important intellectual content
J.R.A.: study concept and design, analysis and interpretation of data, critical revision of the article for important intellectual content, study supervision
Funding
None.
Conflicts of Interest
R.S.D. has served as a consultant for Centaur Labs and Janssen and has received research grant support from Pfizer and Janssen. R.W.W. serves as a consultant for Bristol-Meyers Squibb and has research support from AbbVie, Takeda, and Janssen. M.J.H. has served as a consultant for Bristol-Meyers Squibb and has received research support from Abbvie, Takeda, and Pfizer. J.R.A. serves as a consultant for Abbvie, Janssen, Pfizer, Pandion, Servatus, Finch Therapeutics, Iterative Scopes, BMS, Merck, Summit, Artizan, and Artugen and has grant support from Merck, Pfizer and Janssen. All other authors have no conflicts of interest to disclose.
