Asymptomatic hyperCKemia During Infliximab Therapy in Patients With Inflammatory Bowel Disease

Theodoraki, Eirini; Orfanoudaki, Eleni; Foteinogiannopoulou, Kalliopi; Koutroubakis, Ioannis Ε.

doi:10.1093/ibd/izy088

Cited by 8 publications

(8 citation statements)

References 28 publications

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“…Our findings are also consistent with data for other therapies with an immunosuppressant mode of action used to treat inflammatory diseases, including the JAK inhibitors baricitinib [14], upadacitinib [15][16][17], and TNFi infliximab [20]. In RA clinical studies of baricitinib [14], dose-dependent increases in CK were observed within one week, which plateaued at 8-12 weeks.…”

Section: Discussionsupporting

confidence: 89%

“…Elevated CK levels were among the most common AEs reported in clinical trials of upadacitinib in UC [15], ankylosing spondylitis [16], and RA [17]. In a registry study of infliximab-treated patients with IBD, 30.5% had elevated CK levels (absolute CK > 180 U/L), but none reported persistent symptoms potentially related to myopathy [20]. Other commonly used medications associated with increases in CK include antipsychotics and certain beta blockers [2], as well as statins, where CK elevations 2-10 × ULN occur in around 5% of users [4].…”

Section: Discussionmentioning

confidence: 99%

“…CK elevations with tofacitinib have been shown to be reversible with tofacitinib withdrawal [18] and not associated with myopathies [19]. Asymptomatic, drug-related CK elevations have also been observed with infliximab, a tumor necrosis factor inhibitor (TNFi) used to treat inflammatory bowel disease [20]. However, the origin and implications of CK elevations in patients with UC have not been fully explored.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials

et al. 2020

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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 openlabel, 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.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials

et al. 2020

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“…28 Furthermore, myositis has rarely been observed in patients treated with tumour necrosis factor (TNF) alpha inhibitors 29 and infliximab therapy is rarely associated with increased creatinine kinase levels in the blood. 30 None of our participants terminated the study due to muscle cramps or other signs of muscle alterations and only one participant in the endurance group discontinued the study due to CD-specific symptoms. These findings are consistent with previous investigations with other types of exercise programmes.…”

Section: Discussionmentioning

confidence: 91%

“…Previously, there were controversies about the safety of physical activity in CD patients, as a previous study had suggested that strenuous exercise may cause acute gastrointestinal symptoms such as heartburn and diarrhoea 28 . Furthermore, myositis has rarely been observed in patients treated with tumour necrosis factor (TNF) alpha inhibitors 29 and infliximab therapy is rarely associated with increased creatinine kinase levels in the blood 30 . None of our participants terminated the study due to muscle cramps or other signs of muscle alterations and only one participant in the endurance group discontinued the study due to CD‐specific symptoms.…”

Section: Discussionmentioning

confidence: 99%

Moderate endurance and muscle training is beneficial and safe in patients with quiescent or mildly active Crohn’s disease

et al. 2020

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Background and aims Physical activity is beneficial in several chronic disorders including Crohn′s disease, but the preferred type of exercise is unknown. Our study aimed to examine and compare the safety, feasibility and potential beneficial effects of individual moderate endurance and moderate muscle training in patients with Crohn’s disease. Methods Quiescent or mildly active (Crohn’s disease activity index <220) patients with Crohn’s disease were randomly allocated to either a control, endurance, or muscle training group. Participants exercised individually for 3 months three times per week. Endpoints included dropout rate, disease activity, inflammatory parameters including faecal calprotectin, anthropometric data, quality of life, physical activity and strength. Results A total of 45 patients with Crohn’s disease were randomly allocated. In the endurance group ( n = 17), the dropout rate was significantly higher (47% vs. 13%) compared with the muscle group ( n = 15). In both groups the maximal and average strength in the upper and lower extremities increased significantly (all P < 0.04). In the endurance group emotional function was significantly improved ( P = 0.03). Statistically significant changes of disease activity and other outcome parameters were not observed in this pilot cohort. Conclusion Both individual moderate endurance and muscle training can be safely performed in patients with mild or quiescent Crohn’s disease. Muscle training appears more feasible and may be favoured. Both forms of exercise have beneficial effects on strength. Quality of life increased in both intervention groups, although statistical significance was only reached in one subgroup.

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Selective Inhibition of the MK2 Pathway: Data From a Phase IIa Randomized Clinical Trial in Rheumatoid Arthritis

Gordon

Kivitz

Singhal³

et al. 2023

ACR Open Rheumatology

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Objective. The study objective was to evaluate the safety, tolerability, pharmacodynamics, and preliminary efficacy of ATI-450 with methotrexate in patients with rheumatoid arthritis (RA).Methods. A parallel-assignment, placebo-controlled, investigator-blinded/patient-blinded multicenter study evaluated patients with moderate-to-severe RA aged 18 to 70 years. Eligible patients were randomized (1:1) to ATI-450 50-mg oral tablets twice daily or placebo with a stable weekly dose of methotrexate for 12 weeks. The primary objective was to assess ATI-450 safety and tolerability. The secondary objectives were to assess the median percentage change from baseline high-sensitivity C-reactive protein (hs-CRP) levels, the mean change from baseline in Disease Activity Score in 28 joints based on CRP level (DAS28-CRP) and Rheumatoid Arthritis Magnetic Resonance Imaging Score hand-wrist assessments of synovitis or bone erosion at week 12, and the proportion of patients with American College of Rheumatology 20/50/70 (ACR 20/50/70) and with DAS28-CRP scores of less than 2.6. The exploratory outcomes were change from baseline in endogenous and ex vivo-stimulated cytokine levels.Results. ATI-450 was well tolerated with no severe adverse events reported. ATI-450 reduced median hs-CRP levels by 42% or more at all posttreatment timepoints. In the ATI-450 group, a mean (median) decrease in DAS28-CRP score of 2.0 (2.1) was observed at week 12; proportions of patients with an ACR 20/50/70 response in the per-protocol population were 60%, 33%, and 20%, respectively, at week 12. Endogenous plasma levels of key inflammatory cytokines (tumor necrosis factor α, macrophage inflammatory protein 1β, interleukin 6, interleukin 8) were reduced across the 12 treatment weeks.Conclusion. This is the first clinical study demonstrating that selective mitogen-activated protein kinase (MAPK)activated protein kinase 2 (MK2) pathway blockade leads to a sustained antiinflammatory effect. This suggests that targeting the MK2 pathway mitigates the tachyphylaxis observed with p38 MAPK inhibitors in RA and supports further exploration.

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Asymptomatic hyperCKemia During Infliximab Therapy in Patients With Inflammatory Bowel Disease

Abstract: More than 30% of IBD patients on IFX present asymptomatic persistent and treatment-related hyperCKemia. Further relevant prospective investigation is needed. 10.1093/ibd/izy088_video1izy088.video15778459427001.

Cited by 8 publications

References 28 publications

Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials

Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials

Moderate endurance and muscle training is beneficial and safe in patients with quiescent or mildly active Crohn’s disease

Selective Inhibition of the MK2 Pathway: Data From a Phase IIa Randomized Clinical Trial in Rheumatoid Arthritis

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