Advertisement

Digestive Diseases and Sciences

, Volume 62, Issue 1, pp 197–206 | Cite as

Vedolizumab Therapy Is Associated with an Improvement in Sleep Quality and Mood in Inflammatory Bowel Diseases

  • Betsy W. Stevens
  • Nynke Z. Borren
  • Gabriella Velonias
  • Grace Conway
  • Thom Cleland
  • Elizabeth Andrews
  • Hamed Khalili
  • John G. Garber
  • Ramnik J. Xavier
  • Vijay Yajnik
  • Ashwin N. Ananthakrishnan
Original Article

Abstract

Introduction

Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents.

Methods

This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor α agents (anti-TNF). Sleep quality, depression, and anxiety were measured using validated short-form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed, and regression models were used to identify determinants of sleep quality.

Results

Our study included 160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p = 0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p = 0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6.

Conclusions

Both vedolizumab and anti-TNF biologic therapies were associated with improvement in sleep and mood quality in IBD.

Keywords

Vedolizumab Sleep Biologics Depression Anxiety 

Notes

Author contributions

Stevens, Borren, Velonias, Conway, Cleland, Andrews, Khalili, Garber, Xavier, and Yajnik: study design, data collection, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. Ananthakrishnan: study design, data collection, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and study supervision.

Funding

This work is supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. Ananthakrishnan is supported in part by a Grant from the National Institutes of Health (K23 DK097142).

Compliance with ethical standards

Conflict of interest

Ananthakrishnan has served on scientific advisory boards for Abbvie, Takeda, and Merck.

Supplementary material

10620_2016_4356_MOESM1_ESM.tif (54 kb)
Change in depression and anxiety T-scores with use of anti-tumor necrosis factor α biologic therapy in inflammatory bowel diseases (TIFF 53 kb)

References

  1. 1.
    Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–2078.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142:46–54 e42; quiz e30.Google Scholar
  3. 3.
    Bernstein CN, Loftus EV Jr, Ng SC, et al. Hospitalisations and surgery in Crohn’s disease. Gut. 2012;61:622–629.CrossRefPubMedGoogle Scholar
  4. 4.
    Graff LA, Vincent N, Walker JR, et al. A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflamm Bowel Dis. 2011;17:1882–1889.CrossRefPubMedGoogle Scholar
  5. 5.
    Graff LA, Walker JR, Bernstein CN. Depression and anxiety in inflammatory bowel disease: a review of comorbidity and management. Inflamm Bowel Dis. 2009;15:1105–1118.CrossRefPubMedGoogle Scholar
  6. 6.
    Hommes D, Colombel JF, Emery P, et al. Changing Crohn’s disease management: need for new goals and indices to prevent disability and improve quality of life. J Crohns Colitis. 2012;6:S224–S234.CrossRefPubMedGoogle Scholar
  7. 7.
    Hauser W, Janke KH, Klump B, et al. Anxiety and depression in patients with inflammatory bowel disease: comparisons with chronic liver disease patients and the general population. Inflamm Bowel Dis. 2011;17:621–632.CrossRefPubMedGoogle Scholar
  8. 8.
    Walker JR, Ediger JP, Graff LA, et al. The Manitoba IBD cohort study: a population-based study of the prevalence of lifetime and 12-month anxiety and mood disorders. Am J Gastroenterol. 2008;103:1989–1997.CrossRefPubMedGoogle Scholar
  9. 9.
    Kurina LM, Goldacre MJ, Yeates D, et al. Depression and anxiety in people with inflammatory bowel disease. J Epidemiol Community Health. 2001;55:716–720.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Ananthakrishnan AN. Environmental risk factors for inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2013;9:367–374.Google Scholar
  11. 11.
    Ananthakrishnan AN, Khalili H, Pan A, et al. Association between depressive symptoms and incidence of Crohn’s disease and ulcerative colitis: results from the Nurses’ Health Study. Clin Gastroenterol Hepatol. 2013;11:57–62.CrossRefPubMedGoogle Scholar
  12. 12.
    Lerebours E, Gower-Rousseau C, Merle V, et al. Stressful life events as a risk factor for inflammatory bowel disease onset: a population-based case-control study. Am J Gastroenterol. 2007;102:122–131.CrossRefPubMedGoogle Scholar
  13. 13.
    Tocchi A, Lepre L, Liotta G, et al. Familial and psychological risk factors of ulcerative colitis. Ital J Gastroenterol Hepatol. 1997;29:395–398.PubMedGoogle Scholar
  14. 14.
    Singh S, Graff LA, Bernstein CN. Do NSAIDs, antibiotics, infections, or stress trigger flares in IBD? Am J Gastroenterol. 2009;104:1298–313; quiz 1314.Google Scholar
  15. 15.
    Bernstein CN, Singh S, Graff LA, et al. A prospective population-based study of triggers of symptomatic flares in IBD. Am J Gastroenterol. 2010;105:1994–2002.CrossRefPubMedGoogle Scholar
  16. 16.
    Ananthakrishnan AN, Gainer VS, Perez RG, et al. Psychiatric co-morbidity is associated with increased risk of surgery in Crohn’s disease. Aliment Pharmacol Ther. 2013;37:445–454.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gaines LS, Slaughter JC, Horst SN, et al. Association between affective-cognitive symptoms of depression and exacerbation of Crohn’s disease. Am J Gastroenterol. 2016;111:864–870.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Mikocka-Walus A, Pittet V, Rossel JB, et al. Symptoms of depression and anxiety are independently associated with clinical recurrence of inflammatory bowel disease. Clin Gastroenterol Hepatol. 2016;14:829–835 e1.Google Scholar
  19. 19.
    Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep. 2007;30:1145–1152.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Uthgenannt D, Schoolmann D, Pietrowsky R, et al. Effects of sleep on the production of cytokines in humans. Psychosom Med. 1995;57:97–104.CrossRefPubMedGoogle Scholar
  21. 21.
    Vgontzas AN, Papanicolaou DA, Bixler EO, et al. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab. 1997;82:1313–1316.CrossRefPubMedGoogle Scholar
  22. 22.
    Wilson RG, Stevens BW, Guo AY, et al. High C-reactive protein is associated with poor sleep quality independent of nocturnal symptoms in patients with inflammatory bowel disease. Dig Dis Sci. 2015;60:2136–2143.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Ali T, Madhoun MF, Orr WC, et al. Assessment of the relationship between quality of sleep and disease activity in inflammatory bowel disease patients. Inflamm Bowel Dis. 2013;19:2440–2443.CrossRefPubMedGoogle Scholar
  24. 24.
    Ananthakrishnan AN, Long MD, Martin CF, et al. Sleep disturbance and risk of active disease in patients with Crohn’s disease and ulcerative colitis. Clin Gastroenterol Hepatol. 2013;11:965–971.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Keefer L, Stepanski EJ, Ranjbaran Z, et al. An initial report of sleep disturbance in inactive inflammatory bowel disease. J Clin Sleep Med. 2006;2:409–416.PubMedGoogle Scholar
  26. 26.
    Ananthakrishnan AN, Khalili H, Konijeti GG, et al. Sleep duration affects risk for ulcerative colitis: a prospective cohort study. Clin Gastroenterol Hepatol. 2014;12:1879–1886.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ranjbaran Z, Keefer L, Farhadi A, et al. Impact of sleep disturbances in inflammatory bowel disease. J Gastroenterol Hepatol. 2007;22:1748–1753.CrossRefPubMedGoogle Scholar
  28. 28.
    Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590–1605.CrossRefPubMedGoogle Scholar
  29. 29.
    Ordas I, Eckmann L, Talamini M, et al. Ulcerative colitis. Lancet. 2012;380:1606–1619.CrossRefPubMedGoogle Scholar
  30. 30.
    Sandborn WJ, Feagan BG, Lichtenstein GR. Medical management of mild to moderate Crohn’s disease: evidence-based treatment algorithms for induction and maintenance of remission. Aliment Pharmacol Ther. 2007;26:987–1003.CrossRefPubMedGoogle Scholar
  31. 31.
    Chande N, Patton PH, Tsoulis DJ, et al. Azathioprine or 6-mercaptopurine for maintenance of remission in Crohn’s disease. Cochrane Database Syst Rev. 2015;CD000067. doi: 10.1002/14651858.CD000067.pub3.
  32. 32.
    McDonald JW, Wang Y, Tsoulis DJ, et al. Methotrexate for induction of remission in refractory Crohn’s disease. Cochrane Database Syst Rev. 2014;CD003459. doi: 10.1002/14651858.CD003459.pub4.
  33. 33.
    Danese S, Vuitton L, Peyrin-Biroulet L. Biologic agents for IBD: practical insights. Nat Rev Gastroenterol Hepatol. 2015;12:537–545.CrossRefPubMedGoogle Scholar
  34. 34.
    D’Haens G, Daperno M. Advances in biologic therapy for ulcerative colitis and Crohn’s disease. Curr Gastroenterol Rep. 2006;8:506–512.CrossRefPubMedGoogle Scholar
  35. 35.
    Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.CrossRefPubMedGoogle Scholar
  36. 36.
    Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–721.CrossRefPubMedGoogle Scholar
  37. 37.
    Weinberger JF, Raison CL, Rye DB, et al. Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation. Brain Behav Immun. 2015;47:193–200.CrossRefPubMedGoogle Scholar
  38. 38.
    Zamarron C, Maceiras F, Mera A, et al. Effect of the first infliximab infusion on sleep and alertness in patients with active rheumatoid arthritis. Ann Rheum Dis. 2004;63:88–90.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Ersozlu-Bozkirli ED, Keskek SO, Bozkirli E, et al. The effect of infliximab on depressive symptoms in patients with ankylosing spondylitis. Acta Reumatol Port. 2015;40:262–267.PubMedGoogle Scholar
  40. 40.
    Vavricka SR, Schoepfer A, Scharl M, et al. Extraintestinal Manifestations of Inflammatory Bowel Disease. Inflamm Bowel Dis. 2015;21:1982–1992.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Ananthakrishnan AN, Cagan A, Cai T, et al. Common genetic variants influence circulating vitamin D levels in inflammatory bowel diseases. Inflamm Bowel Dis. 2015;21:2507–2514.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Pringle PL, Stewart KO, Peloquin JM, et al. Body mass index, genetic susceptibility, and risk of complications among individuals with Crohn’s disease. Inflamm Bowel Dis. 2015;21:2304–2310.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Ananthakrishnan AN, Huang H, Nguyen DD, et al. Differential effect of genetic burden on disease phenotypes in Crohn’s disease and ulcerative colitis: analysis of a North American cohort. Am J Gastroenterol. 2014;109:395–400.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1:514.CrossRefPubMedGoogle Scholar
  45. 45.
    Walmsley RS, Ayres RC, Pounder RE, et al. A simple clinical colitis activity index. Gut. 1998;43:29–32.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Irvine EJ, Zhou Q, Thompson AK. The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn’s Relapse Prevention Trial. Am J Gastroenterol. 1996;91:1571–1578.PubMedGoogle Scholar
  47. 47.
    Buysse DJ, Yu L, Moul DE, et al. Development and validation of patient-reported outcome measures for sleep disturbance and sleep-related impairments. Sleep. 2010;33:781–792.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Yu L, Buysse DJ, Germain A, et al. Development of short forms from the PROMIS sleep disturbance and sleep-related impairment item banks. Behav Sleep Med. 2011;10:6–24.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Kappelman MD, Long MD, Martin C, et al. Evaluation of the patient-reported outcomes measurement information system in a large cohort of patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol. 2014;12:1315–1323 e2.Google Scholar
  50. 50.
    Schalet BD, Pilkonis PA, Yu L, et al. Clinical validity of PROMIS depression, anxiety, and anger across diverse clinical samples. J Clin Epidemiol. 2016;73:119–127.CrossRefPubMedGoogle Scholar
  51. 51.
    Irwin MR, Wang M, Campomayor CO, et al. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166:1756–1762.CrossRefPubMedGoogle Scholar
  52. 52.
    Krueger JM, Obal FJ, Fang J, et al. The role of cytokines in physiological sleep regulation. Ann N Y Acad Sci. 2001;933:211–221.CrossRefPubMedGoogle Scholar
  53. 53.
    Krueger JM, Rector DM, Churchill L. Sleep and cytokines. Sleep Med Clin. 2007;2:161–169.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Karadag O, Nakas D, Kalyoncu U, et al. Effect of anti-TNF treatment on sleep problems in ankylosing spondylitis. Rheumatol Int. 2012;32:1909–1913.CrossRefPubMedGoogle Scholar
  55. 55.
    Taylor-Gjevre RM, Gjevre JA, Nair BV, et al. Improved sleep efficiency after anti-tumor necrosis factor alpha therapy in rheumatoid arthritis patients. Ther Adv Musculoskelet Dis. 2011;3:227–233.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Ghia JE, Blennerhassett P, Deng Y, et al. Reactivation of inflammatory bowel disease in a mouse model of depression. Gastroenterology. 2009;136:2280–2288 e1–4.Google Scholar
  57. 57.
    Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71:171–186.CrossRefPubMedGoogle Scholar
  58. 58.
    Horst S, Chao A, Rosen M, et al. Treatment with immunosuppressive therapy may improve depressive symptoms in patients with inflammatory bowel disease. Dig Dis Sci. 2015;60:465–470.CrossRefPubMedGoogle Scholar
  59. 59.
    Guloksuz S, Wichers M, Kenis G, et al. Depressive symptoms in Crohn’s disease: relationship with immune activation and tryptophan availability. PLoS One. 2013;8:e60435.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Ali T, Orr WC. Sleep disturbances and inflammatory bowel disease. Inflamm Bowel Dis. 2014;20:1986–1995.CrossRefPubMedGoogle Scholar
  61. 61.
    Targownik LE, Nugent Z, Singh H, et al. The prevalence and predictors of opioid use in inflammatory bowel disease: a population-based analysis. Am J Gastroenterol. 2014;109:1613–1620.CrossRefPubMedGoogle Scholar
  62. 62.
    Sanford D, Thornley P, Teriaky A, et al. Opioid use is associated with decreased quality of life in patients with Crohn’s disease. Saudi J Gastroenterol. 2014;20:182–187.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Betsy W. Stevens
    • 1
  • Nynke Z. Borren
    • 1
    • 2
  • Gabriella Velonias
    • 1
  • Grace Conway
    • 1
  • Thom Cleland
    • 1
  • Elizabeth Andrews
    • 1
  • Hamed Khalili
    • 1
    • 3
  • John G. Garber
    • 1
    • 3
  • Ramnik J. Xavier
    • 1
    • 3
  • Vijay Yajnik
    • 1
    • 3
  • Ashwin N. Ananthakrishnan
    • 1
    • 3
  1. 1.Division of GastroenterologyMassachusetts General Hospital Crohn’s and Colitis CentreBostonUSA
  2. 2.University of GroningenGroningenThe Netherlands
  3. 3.Harvard Medical SchoolBostonUSA

Personalised recommendations