Health-Related Quality of Life Improvements in Systemic Lupus Erythematosus Derived from a Digital Therapeutic Plus Tele-Health Coaching Intervention: Randomized Controlled Pilot Trial

Faiz Khan, Nora Granville, Raja Malkani, Yash Chathampally, Faiz Khan, Nora Granville, Raja Malkani, Yash Chathampally

Abstract

Background: Systemic lupus erythematosus (SLE), a systemic autoimmune disease with no known cure, remains poorly understood and patients suffer from many gaps in care. Recent work has suggested that dietary and other lifestyle factors play an important role in triggering and propagating SLE in some susceptible individuals. However, the magnitude of influence of these triggers, how to identify pertinent triggers in individual patients, and whether removing these triggers confers clinical benefit is unknown.

Objective: To demonstrate that a digital therapeutic intervention, utilizing a mobile app that allows self-tracking of dietary, environmental, and lifestyle triggers, paired with telehealth coaching, added to usual care, improves quality of life in patients with SLE compared with usual care alone.

Methods: In this randomized controlled pilot study, adults with SLE were assigned to a 16-week digital therapeutic intervention plus usual care or usual care alone. Primary outcome measures were changes from baseline to 16 weeks on 3 validated health-related quality of life (HRQoL) tools: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Brief Pain Inventory-Short Form (BPI-SF), and Lupus Quality of Life (LupusQoL).

Results: A total of 50 patients were randomized (23 control, 27 intervention). In per-protocol analysis, the intervention group achieved significantly greater improvement than the control group in 9 of 11 domains: FACIT-F (34% absolute improvement for the intervention group vs -1% for the control group, P<.001), BPI-SF-Pain Interference (25% vs 0%, P=.02), LupusQoL-Planning (17% vs 0%, P=.004), LupusQoL-Pain (13% vs 0%, P=.004), LupusQoL-Emotional Health (21% vs 4%, P=.02), and LupusQoL-Fatigue (38% vs 13%, P<.001) were significant when controlling for multiple comparisons; BPI-SF-Pain Severity (13% vs -6%, P=.049), LupusQoL-Physical Health (17% vs 3%, P=.049), and LupusQoL-Burden to Others (33% vs 4%, P=.04) were significant at an unadjusted 5% significance level.

Conclusions: A digital therapeutic intervention that pairs self-tracking with telehealth coaching to identify and remove dietary, environmental, and lifestyle symptom triggers resulted in statistically significant, clinically meaningful improvements in HRQoL when added to usual care in patients with SLE.

Trial registration: ClinicalTrials.gov NCT03426384; https://ichgcp.net/clinical-trials-registry/NCT03426384.

Keywords: autoimmunity; dietary intervention; digital health; digital therapeutic; environmental influences on autoimmunity; food as medicine; health-related quality of life; lifestyle medicine; mobile health; systemic lupus erythematosus.

Conflict of interest statement

Conflicts of Interest: FK and RM have received standard financial stipends from Mymee, Inc. and have no other disclosures to make. NG and YC have nothing to declare.

©Faiz Khan, Nora Granville, Raja Malkani, Yash Chathampally. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.10.2020.

Figures

Figure 1
Figure 1
Mobile app for entering symptoms and dietary, environmental, and lifestyle inputs.
Figure 2
Figure 2
Participant flow. ITT: intention to treat; PP: per protocol.
Figure 3
Figure 3
Absolute and Relative Improvement by Domain. Absolute improvement was median change from baseline to endpoint divided by total possible domain score. Relative improvement was median change divided by the median baseline domain score. Changes in BPI-SF-pain interference and BPI-SF-pain severity are converted to positive % for consistency with other domains. P-values are from the Mann–Whitney U test comparing changes in score between intervention and control groups. P-values are unadjusted. Although both ITT intervention and control groups achieved significant improvement in some domains, when the groups were compared, no statistically significant differences were found. aStatistically significant after using the Benjamini–Hochberg adjustment bStatistically significant at an unadjusted two-sided significance level of 5%. FACIT: Functional Assessment of Chronic Illness Therapy; ITT: intention to treat.
Figure 4
Figure 4
Change over time in FACIT-Fatigue and LupusQoL-Fatigue. FACIT: Functional Assessment of Chronic Illness Therapy; LupusQoL: Lupus Quality of Life.
Figure 5
Figure 5
Change over time in LupusQoL-Physical Health, LupusQoL-Pain and LupusQoL-Burden to Others. LupusQoL: Lupus Quality of Life.
Figure 6
Figure 6
Change over time in LupusQoL-Planning, LupusQoL-Relationships, LupusQoL-Emotional Health and LupusQoL-Body Image. LupusQoL: Lupus Quality of Life.
Figure 7
Figure 7
Change over time in BPI-SF Pain Severity and BPI-SF Pain Interference. BPI-SF: Brief Pain Index-Short Form.

References

    1. Lupus Facts and Statistics. 2016. Oct 06, [2020-08-03]. .
    1. Lightstone L, Doria A, Wilson H, Ward FL, Larosa M, Bargman JM. Can we manage lupus nephritis without chronic corticosteroids administration? Autoimmun Rev. 2018 Jan;17(1):4–10. doi: 10.1016/j.autrev.2017.11.002.
    1. Pons-Estel GJ, Alarcón Graciela S, Scofield L, Reinlib L, Cooper GS. Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum. 2010 Feb;39(4):257–68. doi: 10.1016/j.semarthrit.2008.10.007.
    1. Bernatsky S, Boivin J, Joseph L, Manzi S, Ginzler E, Gladman DD, Urowitz M, Fortin PR, Petri M, Barr S, Gordon C, Bae S, Isenberg D, Zoma A, Aranow C, Dooley M, Nived O, Sturfelt G, Steinsson K, Alarcón G, Senécal J, Zummer M, Hanly J, Ensworth S, Pope J, Edworthy S, Rahman A, Sibley J, El-Gabalawy H, McCarthy T, St Pierre Y, Clarke A, Ramsey-Goldman R. Mortality in systemic lupus erythematosus. Arthritis Rheum. 2006 Aug;54(8):2550–7. doi: 10.1002/art.21955. doi: 10.1002/art.21955.
    1. Yen EY, Shaheen M, Woo JMP, Mercer N, Li N, McCurdy DK, Karlamangla A, Singh RR. 46-Year Trends in Systemic Lupus Erythematosus Mortality in the United States, 1968 to 2013: A Nationwide Population-Based Study. Ann Intern Med. 2017 Dec 05;167(11):777–785. doi: 10.7326/M17-0102.
    1. Almehed K, Carlsten H, Forsblad-d'Elia H. Health-related quality of life in systemic lupus erythematosus and its association with disease and work disability. Scand J Rheumatol. 2010;39(1):58–62. doi: 10.3109/03009740903124408.
    1. Olesińska M, Saletra A. Quality of life in systemic lupus erythematosus and its measurement. Reumatologia. 2018;56(1):45–54. doi: 10.5114/reum.2018.74750.
    1. Utset TO, Chohan S, Booth SA, Laughlin JC, Kocherginsky M, Schmitz A. Correlates of formal work disability in an urban university systemic lupus erythematosus practice. J Rheumatol. 2008 Jun;35(6):1046–52.
    1. Yen EY, Singh RR. Brief Report: Lupus-An Unrecognized Leading Cause of Death in Young Females: A Population-Based Study Using Nationwide Death Certificates, 2000-2015. Arthritis Rheumatol. 2018 Aug;70(8):1251–1255. doi: 10.1002/art.40512. doi: 10.1002/art.40512.
    1. Mazzone R, Zwergel C, Artico M, Taurone S, Ralli M, Greco A, Mai A. The emerging role of epigenetics in human autoimmune disorders. Clin Epigenetics. 2019 Feb 26;11(1):34. doi: 10.1186/s13148-019-0632-2.
    1. Riscuta G, Xi D, Pierre-Victor D, Starke-Reed P, Khalsa J, Duffy L. Diet, Microbiome, and Epigenetics in the Era of Precision Medicine. Methods Mol Biol. 2018;1856:141–156. doi: 10.1007/978-1-4939-8751-1_8.
    1. Pan Y, Ke H, Yan Z, Geng Y, Asner N, Palani S, Munirathinam G, Dasari S, Nitiss KC, Bliss S, Patel P, Shen H, Reardon CA, Getz GS, Chen A, Zheng G. The western-type diet induces anti-HMGB1 autoimmunity in Apoe(-/-) mice. Atherosclerosis. 2016 Aug;251:31–38. doi: 10.1016/j.atherosclerosis.2016.05.027.
    1. Mu Q, Zhang H, Luo XM. SLE: Another Autoimmune Disorder Influenced by Microbes and Diet? Front Immunol. 2015;6:608. doi: 10.3389/fimmu.2015.00608. doi: 10.3389/fimmu.2015.00608.
    1. Parks CG, de Souza Espindola Santos A, Barbhaiya M, Costenbader KH. Understanding the role of environmental factors in the development of systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2017 Jun;31(3):306–320. doi: 10.1016/j.berh.2017.09.005.
    1. Hardy TM, Tollefsbol TO. Epigenetic diet: impact on the epigenome and cancer. Epigenomics. 2011 Aug;3(4):503–18. doi: 10.2217/epi.11.71.
    1. Young KA, Munroe ME, Harley JB, Guthridge JM, Kamen DL, Gilkensen GS, Weisman MH, Karp DR, Wallace DJ, James JA, Norris JM. Less than 7 hours of sleep per night is associated with transitioning to systemic lupus erythematosus. Lupus. 2018 Aug;27(9):1524–1531. doi: 10.1177/0961203318778368.
    1. Gaine ME, Chatterjee S, Abel T. Sleep Deprivation and the Epigenome. Front Neural Circuits. 2018;12:14. doi: 10.3389/fncir.2018.00014. doi: 10.3389/fncir.2018.00014.
    1. Hsiao Y, Chen Y, Tseng C, Wu L, Lin W, Su VY, Perng D, Chang S, Chen Y, Chen T, Lee Y, Chou K. Sleep disorders and increased risk of autoimmune diseases in individuals without sleep apnea. Sleep. 2015 Apr 01;38(4):581–6. doi: 10.5665/sleep.4574.
    1. Song H, Fang F, Tomasson G, Arnberg FK, Mataix-Cols D, Fernández de la Cruz L, Almqvist C, Fall K, Valdimarsdóttir UA. Association of Stress-Related Disorders With Subsequent Autoimmune Disease. JAMA. 2018 Jun 19;319(23):2388–2400. doi: 10.1001/jama.2018.7028.
    1. Gudsnuk K, Champagne FA. Epigenetic influence of stress and the social environment. ILAR J. 2012;53(3-4):279–88. doi: 10.1093/ilar.53.3-4.279.
    1. Lee RS, Tamashiro KLK, Yang X, Purcell RH, Harvey A, Willour VL, Huo Y, Rongione M, Wand GS, Potash JB. Chronic corticosterone exposure increases expression and decreases deoxyribonucleic acid methylation of Fkbp5 in mice. Endocrinology. 2010 Sep;151(9):4332–43. doi: 10.1210/en.2010-0225.
    1. Simpson R, Kunz H, Agha N, Graff R. Exercise and the Regulation of Immune Functions. Prog Mol Biol Transl Sci. 2015;135:355–80. doi: 10.1016/bs.pmbts.2015.08.001.
    1. Zhang FF, Cardarelli R, Carroll J, Zhang S, Fulda KG, Gonzalez K, Vishwanatha JK, Morabia A, Santella RM. Physical activity and global genomic DNA methylation in a cancer-free population. Epigenetics. 2011 Mar;6(3):293–9. doi: 10.4161/epi.6.3.14378.
    1. Manzi S, Raymond S, Tse K, Peña Y, Anderson A, Arntsen K, Bae S, Bruce I, Dörner T, Getz K, Hanrahan L, Kao A, Morand E, Rovin B, Schanberg LE, Von Feldt JM, Werth VP, Costenbader K. Global consensus building and prioritisation of fundamental lupus challenges: the ALPHA project. Lupus Sci Med. 2019;6(1):e000342. doi: 10.1136/lupus-2019-000342.
    1. Examples of Device Software Functions the FDA Regulates. Silver Spring, MD: Food and Drug Administration; 2019. Sep 26, [2020-08-02]. .
    1. Coravos A, Khozin S, Mandl KD. Developing and adopting safe and effective digital biomarkers to improve patient outcomes. NPJ Digit Med. 2019;2(1):40. doi: 10.1038/s41746-019-0090-4. doi: 10.1038/s41746-019-0090-4.
    1. Gordon WJ, Landman A, Zhang H, Bates DW. Beyond validation: getting health apps into clinical practice. NPJ Digit Med. 2020;3:14. doi: 10.1038/s41746-019-0212-z. doi: 10.1038/s41746-019-0212-z.
    1. Us in Lupus. [2020-08-02]. .
    1. Track the Symptoms of Lupus with this Symptom Tracking App. [2020-08-02]. .
    1. My Lupus Log. .
    1. Mango Health. [2020-09-18].
    1. McElhone K, Abbott J, Shelmerdine J, Bruce IN, Ahmad Y, Gordon C, Peers K, Isenberg D, Ferenkeh-Koroma A, Griffiths B, Akil M, Maddison P, Teh L. Development and validation of a disease-specific health-related quality of life measure, the LupusQol, for adults with systemic lupus erythematosus. Arthritis Rheum. 2007 Aug 15;57(6):972–9. doi: 10.1002/art.22881. doi: 10.1002/art.22881.
    1. Lai J, Beaumont JL, Ogale S, Brunetta P, Cella D. Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial. J Rheumatol. 2011 Apr;38(4):672–9. doi: 10.3899/jrheum.100799.
    1. Mease PJ, Spaeth M, Clauw DJ, Arnold LM, Bradley LA, Russell IJ, Kajdasz DK, Walker DJ, Chappell AS. Estimation of minimum clinically important difference for pain in fibromyalgia. Arthritis Care Res (Hoboken) 2011 Jun;63(6):821–6. doi: 10.1002/acr.20449. doi: 10.1002/acr.20449.
    1. Izadi Z, Gandrup J, Katz PP, Yazdany J. Patient-reported outcome measures for use in clinical trials of SLE: a review. Lupus Sci Med. 2018;5(1):e000279. doi: 10.1136/lupus-2018-000279.
    1. Naegeli AN, Tomaszewski EL, Al Sawah S. Psychometric validation of the Brief Pain Inventory-Short Form in patients with systemic lupus erythematosus in the United States. Lupus. 2015 Nov;24(13):1377–83. doi: 10.1177/0961203315588972.
    1. McElhone K, Abbott J, Sutton C, Mullen M, Lanyon P, Rahman A, Yee C, Akil M, Bruce IN, Ahmad Y, Gordon C, Teh L. Sensitivity to Change and Minimal Important Differences of the LupusQoL in Patients With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken) 2016 Oct;68(10):1505–13. doi: 10.1002/acr.22850. doi: 10.1002/acr.22850.
    1. Allaire S. Is work disability associated with systemic lupus erythematosus modifiable? J Rheumatol. 2008 Jun;35(6):953–5.
    1. Scofield L, Reinlib L, Alarcón GS, Cooper GS. Employment and disability issues in systemic lupus erythematosus: a review. Arthritis Rheum. 2008 Oct 15;59(10):1475–9. doi: 10.1002/art.24113. doi: 10.1002/art.24113.
    1. Connolly D, Fitzpatrick C, O'Toole L, Doran M, O'Shea F. Impact of Fatigue in Rheumatic Diseases in the Work Environment: A Qualitative Study. Int J Environ Res Public Health. 2015 Oct 28;12(11):13807–22. doi: 10.3390/ijerph121113807.
    1. Arroyo Hornero R, Hamad I, Côrte-Real B, Kleinewietfeld M. The Impact of Dietary Components on Regulatory T Cells and Disease. Front Immunol. 2020;11:253. doi: 10.3389/fimmu.2020.00253. doi: 10.3389/fimmu.2020.00253.
    1. Hussain N. N282: Effect of gluten containing diet on pristane induced lupus prone mice. Lupus Science and Medicine. 2017;4(Suppl_1):A129–A130. doi: 10.1136/lupus-2017-000215.282.
    1. Coucke F. Food intolerance in patients with manifest autoimmunity. Observational study. Autoimmun Rev. 2018 Nov;17(11):1078–1080. doi: 10.1016/j.autrev.2018.05.011.
    1. Constantin M, Nita IE, Olteanu R, Constantin T, Bucur S, Matei C, Raducan A. Significance and impact of dietary factors on systemic lupus erythematosus pathogenesis. Exp Ther Med. 2019 Feb;17(2):1085–1090. doi: 10.3892/etm.2018.6986.
    1. Seguin D, Peschken C, Dolovich C, Grymonpre R, St JP, Tisseverasinghe A. Polypharmacy and potentially inappropriate medication use in young vs older adults with SLE (abstract). 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. 2019.
    1. Leelakanok N, Holcombe AL, Lund BC, Gu X, Schweizer ML. Association between polypharmacy and death: A systematic review and meta-analysis. J Am Pharm Assoc (2003) 2017;57(6):729–738.e10. doi: 10.1016/j.japh.2017.06.002.
    1. Manfredo Vieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Khan N, Costa FRC, Tiniakou E, Greiling T, Ruff W, Barbieri A, Kriegel C, Mehta SS, Knight JR, Jain D, Goodman AL, Kriegel MA. Translocation of a gut pathobiont drives autoimmunity in mice and humans. Science. 2018 Mar 09;359(6380):1156–1161. doi: 10.1126/science.aar7201.
    1. He B, Hoang TK, Wang T, Ferris M, Taylor CM, Tian X, Luo M, Tran DQ, Zhou J, Tatevian N, Luo F, Molina JG, Blackburn MR, Gomez TH, Roos S, Rhoads JM, Liu Y. Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors. J Exp Med. 2017 Jan;214(1):107–123. doi: 10.1084/jem.20160961.
    1. Mu Q, Kirby J, Reilly CM, Luo XM. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017;8:598. doi: 10.3389/fimmu.2017.00598. doi: 10.3389/fimmu.2017.00598.
    1. Hevia A, Milani C, López P, Cuervo A, Arboleya S, Duranti S, Turroni F, González S, Suárez A, Gueimonde M, Ventura M, Sánchez B, Margolles A. Intestinal dysbiosis associated with systemic lupus erythematosus. mBio. 2014 Sep 30;5(5):e01548–14. doi: 10.1128/mBio.01548-14.
    1. NIH Integrative Human Microbiome Project. [2008-05-20].
    1. Jolly M, Katz P. Systemic lupus erythematosus: The promise of PROMIS - is it ready for prime time in SLE? Nat Rev Rheumatol. 2017 Aug;13(8):453–454. doi: 10.1038/nrrheum.2017.100.
    1. Mahieu M, Yount S, Ramsey-Goldman R. Patient-Reported Outcomes in Systemic Lupus Erythematosus. Rheum Dis Clin North Am. 2016 May;42(2):253–263. doi: 10.1016/j.rdc.2016.01.001.
    1. More People Search for Health Online. . [2020-09-28]. .
    1. Mobile Fact Sheet. [2020-09-20].

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