TY - JOUR
T1 - Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis
T2 - Results from Clinical Trials
AU - Panaccione, Remo
AU - Isaacs, John D.
AU - Chen, Lea Ann
AU - Wang, Wenjin
AU - Marren, Amy
AU - Kwok, Kenneth
AU - Wang, Lisy
AU - Chan, Gary
AU - Su, Chinyu
N1 - Funding Information:
These studies were sponsored by Pfizer Inc. Medical writing support was funded by Pfizer Inc. Acknowledgments
Funding Information:
The authors would like to thank the patients, investigators, and trial teams who were involved in the tofacitinib clinical trial programs. Medical writing support, under the guidance of the authors, was provided by Daniel Binks, PhD, CMC Connect, McCann Health Medical Communications, and was funded by Pfizer Inc, New York, NY, USA, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461?464). John D. Isaacs is supported by the NIHR Newcastle Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
Funding Information:
The authors would like to thank the patients, investigators, and trial teams who were involved in the tofacitinib clinical trial programs. Medical writing support, under the guidance of the authors, was provided by Daniel Binks, PhD, CMC Connect, McCann Health Medical Communications, and was funded by Pfizer Inc, New York, NY, USA, in accordance with Good Publication Practice (GPP3) guidelines (Ann Intern Med. 2015;163:461–464). John D. Isaacs is supported by the NIHR Newcastle Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/8
Y1 - 2021/8
N2 - Background: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. Methods: Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. Results: Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1–134.1) versus 19.2 U/L (8.5–29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1–63.7), 90.3 (51.9–128.7), and 115.6 U/L (91.6–139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. Conclusions: In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. Trial Registration: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.
AB - Background: Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. Methods: Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. Results: Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1–134.1) versus 19.2 U/L (8.5–29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1–63.7), 90.3 (51.9–128.7), and 115.6 U/L (91.6–139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. Conclusions: In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. Trial Registration: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.
KW - Creatine kinase
KW - Inflammatory bowel disease
KW - Safety
KW - Tofacitinib
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=85089703696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089703696&partnerID=8YFLogxK
U2 - 10.1007/s10620-020-06560-4
DO - 10.1007/s10620-020-06560-4
M3 - Article
C2 - 32816215
AN - SCOPUS:85089703696
SN - 0163-2116
VL - 66
SP - 2732
EP - 2743
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 8
ER -