Potential Mechanism of Fatigue Induction and Its Management by JAK Inhibitors in Inflammatory Rheumatic Diseases

References

• Surowiec I, Gjesdal CG, Jonsson G, et al. Metabolomics study of fatigue in patients with rheumatoid arthritis naive to biological treatment. Rheumatol Int. 2016;36(5):703–711. doi:10.1007/s00296-016-3426-2
   PubMed Web of Science ®Google Scholar
• Bower JE. Cancer-related fatigue--mechanisms, risk factors, and treatments. Nature reviews. Clin Oncol. 2014;11(10):597–609.
   Web of Science ®Google Scholar
• Norheim KB, Jonsson G, Omdal R. Biological mechanisms of chronic fatigue. Rheumatology. 2011;50(6):1009–1018.
   PubMed Web of Science ®Google Scholar
• Korte SM, Straub RH. Fatigue in inflammatory rheumatic disorders: pathophysiological mechanisms. Rheumatology. 2019;58(Suppl 5):v35–v50.
   PubMedGoogle Scholar
• Versteeg GA, Ten Klooster PM, van de Laar M. Fatigue is associated with disease activity in some, but not all, patients living with rheumatoid arthritis: disentangling “between-person” and “within-person” associations. BMC Rheumatol. 2022;6(1):3.
   PubMedGoogle Scholar
• Druce KL, Basu N. Predictors of fatigue in rheumatoid arthritis. Rheumatology. 2019;58(Suppl 5):v29–v34.
   PubMedGoogle Scholar
• Westhoff G, Dorner T, Zink A. Fatigue and depression predict physician visits and work disability in women with primary Sjogren’s syndrome: results from a cohort study. Rheumatology. 2012;51(2):262–269.
   PubMed Web of Science ®Google Scholar
• Pollard LC, Choy EH, Gonzalez J, Khoshaba B, Scott DL. Fatigue in rheumatoid arthritis reflects pain, not disease activity. Rheumatology. 2006;45(7):885–889.
   PubMed Web of Science ®Google Scholar
• Husted JA, Gladman DD, Farewell VT, Cook RJ. Health-related quality of life of patients with psoriatic arthritis: a comparison with patients with rheumatoid arthritis. Arthritis Rheum. 2001;45(2):151–158.
   PubMedGoogle Scholar
• Dagfinrud H, Vollestad NK, Loge JH, Kvien TK, Mengshoel AM. Fatigue in patients with ankylosing spondylitis: a comparison with the general population and associations with clinical and self-reported measures. Arthritis Rheum. 2005;53(1):5–11. doi:10.1002/art.20910
   PubMed Web of Science ®Google Scholar
• Massalska M, Maslinski W, Ciechomska M. Small molecule inhibitors in the treatment of rheumatoid arthritis and beyond: latest updates and potential strategy for fighting COVID-19. Cells. 2020;9(8):1876. doi:10.3390/cells9081876
   PubMed Web of Science ®Google Scholar
• Pope JE. Management of Fatigue in Rheumatoid Arthritis. RMD Open. 2020;6(1):e001084. doi:10.1136/rmdopen-2019-001084
   PubMed Web of Science ®Google Scholar
• Howard Tripp N, Tarn J, Natasari A, et al. Fatigue in primary Sjogren’s syndrome is associated with lower levels of proinflammatory cytokines. RMD Open. 2016;2(2):e000282. doi:10.1136/rmdopen-2016-000282
   PubMedGoogle Scholar
• Muskardin TLW, Niewold TB. Type I interferon in rheumatic diseases. Nat Rev Rheumatol. 2018;14(4):214–228. doi:10.1038/nrrheum.2018.31
   PubMed Web of Science ®Google Scholar
• Druce KL, Bhattacharya Y, Jones GT, Macfarlane GJ, Basu N. Most patients who reach disease remission following anti-TNF therapy continue to report fatigue: results from the British society for rheumatology biologics register for rheumatoid arthritis. Rheumatology. 2016;55(10):1786–1790. doi:10.1093/rheumatology/kew241
   PubMed Web of Science ®Google Scholar
• Almeida C, Choy EH, Hewlett S, et al. Biologic interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst. Rev. 2016;2016(6):CD008334. doi:10.1002/14651858.CD008334.pub2
   PubMedGoogle Scholar
• Bonek K, Roszkowski L, Massalska M, Maslinski W, Ciechomska M. Biologic drugs for rheumatoid arthritis in the context of Biosimilars, Genetics, Epigenetics and COVID-19 Treatment. Cells. 2021;10(2):323. doi:10.3390/cells10020323
   PubMed Web of Science ®Google Scholar
• Norheim KB, Imgenberg-Kreuz J, Alexsson A, et al. Genetic variants at the RTP4/MASP1 locus are associated with fatigue in Scandinavian patients with primary Sjögren’s syndrome. RMD Open. 2021;7(3):e001832. doi:10.1136/rmdopen-2021-001832
   PubMed Web of Science ®Google Scholar
• Deepak HB, Prince SE, Deshpande P. Effect of baricitinib in regulating programmed death 1 and ligand programmed cell death ligand 1 through JAK/STAT pathway in psoriasis. Indian J Pharmacol. 2022;54(3):183–193. doi:10.4103/ijp.ijp_1089_20
   PubMed Web of Science ®Google Scholar
• Morris G, Berk M, Galecki P, Walder K, Maes M. The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases. Mol Neurobiol. 2016;53(2):1195–1219.
   PubMed Web of Science ®Google Scholar
• Teleanu DM, Niculescu AG, Lungu II, et al. An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. Int J Mol Sci. 2022;23:11.
   Web of Science ®Google Scholar
• Avalos I, Chung CP, Oeser A, et al. Oxidative stress in systemic lupus erythematosus: relationship to disease activity and symptoms. Lupus. 2007;16(3):195–200.
   PubMed Web of Science ®Google Scholar
• Sharpe M, Wilks D. Fatigue. BMJ. 2002;325(7362):480–483.
   PubMed Web of Science ®Google Scholar
• Davies K, Dures E, Ng WF. Fatigue in inflammatory rheumatic diseases: current knowledge and areas for future research. Nat Rev Rheumatol. 2021;17(11):651–664.
   PubMed Web of Science ®Google Scholar
• McCusker RH, Kelley KW. Immune-neural connections: how the immune system’s response to infectious agents influences behavior. J Exp Biol. 2013;216(Pt 1):84–98.
   PubMed Web of Science ®Google Scholar
• Schaible HG. Nociceptive neurons detect cytokines in arthritis. Arthritis Res Ther. 2014;16(5):470.
   PubMed Web of Science ®Google Scholar
• Eddleston M, Mucke L. Molecular profile of reactive astrocytes--implications for their role in neurologic disease. Neuroscience. 1993;54(1):15–36.
   PubMed Web of Science ®Google Scholar
• Schwarcz R, Pellicciari R. Manipulation of brain kynurenines: glial targets, neuronal effects, and clinical opportunities. J Pharmacol Exp Ther. 2002;303(1):1–10.
   PubMed Web of Science ®Google Scholar
• Maes M, Leonard BE, Myint AM, Kubera M, Verkerk R. The new ‘5-HT’ hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(3):702–721.
   PubMed Web of Science ®Google Scholar
• Sas K, Robotka H, Toldi J, Vecsei L. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci. 2007;257(1–2):221–239.
   PubMed Web of Science ®Google Scholar
• Akesson K, Pettersson S, Stahl S, et al. Kynurenine pathway is altered in patients with SLE and associated with severe fatigue. Lupus Sci Med. 2018;5(1):e000254.
   PubMed Web of Science ®Google Scholar
• Schrocksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta. 2006;364(1–2):82–90.
   PubMed Web of Science ®Google Scholar
• Tykocinski LO, Lauffer AM, Bohnen A, et al. Synovial Fibroblasts selectively suppress Th1 Cell Responses through IDO1-mediated tryptophan catabolism. J Immunol. 2017;198(8):3109–3117.
   PubMed Web of Science ®Google Scholar
• Massalska M, Kuca-Warnawin E, Janicka I, et al. Survival of lymphocytes is not restricted by IDO-expressing fibroblast from rheumatoid arthritis patients. Immunopharmacol Immunotoxicol. 2019;41(2):214–223.
   PubMed Web of Science ®Google Scholar
• Yao N, Tretter T, Kvacskay P, et al. Targeting of janus kinases limits pro-inflammatory but also immunosuppressive circuits in the crosstalk between synovial fibroblasts and lymphocytes. Biomedicines. 2021;9:10.
   Web of Science ®Google Scholar
• Lamba M, Wang R, Fletcher T, Alvey C, Kushner J, Stock TC. Extended-release once-daily formulation of tofacitinib: evaluation of pharmacokinetics compared with immediate-release tofacitinib and impact of food. J Clin Pharmacol. 2016;56(11):1362–1371.
   PubMed Web of Science ®Google Scholar
• Shi JG, Chen X, Lee F, et al. The pharmacokinetics, pharmacodynamics, and safety of baricitinib, an oral JAK 1/2 inhibitor, in healthy volunteers. J Clin Pharmacol. 2014;54(12):1354–1361.
   PubMed Web of Science ®Google Scholar
• Mohamed MF, Camp HS, Jiang P, Padley RJ, Asatryan A, Othman AA. Pharmacokinetics, safety and tolerability of ABT-494, a novel selective JAK 1 inhibitor, in healthy volunteers and subjects with rheumatoid arthritis. Clin Pharmacokinet. 2016;55(12):1547–1558.
   PubMed Web of Science ®Google Scholar
• Larssen E, Brede C, Hjelle A, et al. Fatigue in primary Sjogren’s syndrome: a proteomic pilot study of cerebrospinal fluid. SAGE Open Medicine. 2019;7:2050312119850390.
   Web of Science ®Google Scholar
• Holdren M, Schieir O, Bartlett SJ, et al. Improvements in fatigue lag behind disease remission in early rheumatoid arthritis: results from the Canadian early arthritis cohort. Arthrit Rheumatol. 2021;73(1):53–60.
   PubMed Web of Science ®Google Scholar
• Dowell NG, Bouyagoub S, Tibble J, Voon V, Cercignani M, Harrison NA. Interferon-alpha-induced changes in NODDI predispose to the development of fatigue. Neuroscience. 2019;403:111–117.
   PubMed Web of Science ®Google Scholar
• Davies K, Mirza K, Tarn J, et al. Fatigue in primary Sjogren’s syndrome (pSS) is associated with lower levels of proinflammatory cytokines: a validation study. Rheumatol Int. 2019;39(11):1867–1873.
   PubMed Web of Science ®Google Scholar
• Azizoddin DR, Gandhi N, Weinberg S, Sengupta M, Nicassio PM, Jolly M. Fatigue in systemic lupus: the role of disease activity and its correlates. Lupus. 2019;28(2):163–173.
   PubMed Web of Science ®Google Scholar
• Wu Q, Inman RD, Davis KD. Tumor necrosis factor inhibitor therapy in ankylosing spondylitis: differential effects on pain and fatigue and brain correlates. Pain. 2015;156(2):297–304.
   PubMed Web of Science ®Google Scholar
• Reygaerts T, Mitrovic S, Fautrel B, Gossec L. Effect of biologics on fatigue in psoriatic arthritis: a systematic literature review with meta-analysis. Joint Bone Spine. 2018;85(4):405–410.
   PubMed Web of Science ®Google Scholar
• Atzeni F, Nucera V, Masala IF, Sarzi-Puttini P, Bonitta G. Il-6 Involvement in pain, fatigue and mood disorders in rheumatoid arthritis and the effects of Il-6 inhibitor sarilumab. Pharmacol Res. 2019;149:104402.
   PubMed Web of Science ®Google Scholar
• Wu P, Wu X, Zhou G, et al. P2X7 receptor-induced bone cancer pain by regulating microglial activity via NLRP3/IL-1beta Signaling. Pain Physician. 2022;25(8):E1199–E1210.
   PubMed Web of Science ®Google Scholar
• Alciati A, Di Carlo M, Siragusano C, Palumbo A, Masala IF, Atzeni F. Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis. Expert Opin Biol Ther. 2022;22(10):1311–1322.
   PubMed Web of Science ®Google Scholar
• Moulton VR. Sex Hormones in Acquired Immunity and Autoimmune Disease. Front Immunol. 2018;9:2279.
   PubMed Web of Science ®Google Scholar
• Sokka T, Toloza S, Cutolo M, et al. Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study. Arthritis Res Ther. 2009;11(1):R7.
   PubMed Web of Science ®Google Scholar
• Fleischmann R, Schiff M, van der Heijde D, et al. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthrit Rheumatol. 2017;69(3):506–517.
   PubMed Web of Science ®Google Scholar
• Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The committee on outcome measures in rheumatoid arthritis clinical trials. Arthritis Rheum. 1993;36(6):729–740.
   PubMed Web of Science ®Google Scholar
• Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis. Arthrit Care Res. 2016;68(1):1–25.
   PubMed Web of Science ®Google Scholar
• Smolen JS, Landewe R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960–977.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration. Guidance for industry rheumatoid arthritis: developing drug products for treatment https://www.fda.gov/regulatory-information/search-fda-guidance-documents/rheumatoid-arthritis-developing-drug-products-treatment. Accessed August 11, 2023.
   Google Scholar
• Whalley D, McKenna SP, de Jong Z, van der Heijde D. Quality of life in rheumatoid arthritis. Br J Rheumatol. 1997;36(8):884–888.
   PubMedGoogle Scholar
• Cole JC, Motivala SJ, Khanna D, Lee JY, Paulus HE, Irwin MR. Validation of single-factor structure and scoring protocol for the Health Assessment Questionnaire-Disability Index. Arthritis Rheum. 2005;53(4):536–542.
   PubMedGoogle Scholar
• Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008;59(6):762–784.
   PubMed Web of Science ®Google Scholar
• Luqmani R, Hennell S, Estrach C, et al. British society for rheumatology and British health professionals in rheumatology guideline for the management of rheumatoid arthritis (after the first 2 years). Rheumatology. 2009;48(4):436–439.
   PubMed Web of Science ®Google Scholar
• Jansen JP, Buckley F, Dejonckheere F, Ogale S. Comparative efficacy of biologics as monotherapy and in combination with methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients with an inadequate response to conventional DMARDs--a systematic review and network meta-analysis. Health Qual Life Outcomes. 2014;12:102.
   PubMed Web of Science ®Google Scholar
• Ramey DR, Raynauld JP, Fries JF. The health assessment questionnaire 1992: status and review. Arthritis Care Res. 1992;5(3):119–129.
   PubMedGoogle Scholar
• Strand V, Singh JA. Improved health-related quality of life with effective disease-modifying antirheumatic drugs: evidence from randomized controlled trials. Am J Manag Care. 2008;14(4):234–254.
   PubMed Web of Science ®Google Scholar
• Mathias SD, Colwell HH, Miller DP, Moreland LW, Buatti M, Wanke L. Health-related quality of life and functional status of patients with rheumatoid arthritis randomly assigned to receive etanercept or placebo. Clin Ther. 2000;22(1):128–139.
   PubMed Web of Science ®Google Scholar
• van de Putte LB, Atkins C, Malaise M, et al. Efficacy and safety of Adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed. Ann Rheum Dis. 2004;63(5):508–516.
   PubMed Web of Science ®Google Scholar
• Holten K, Paulshus Sundlisater N, Lillegraven S, et al. Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment. Ann Rheum Dis. 2022;81(3):344–350.
   PubMed Web of Science ®Google Scholar
• Calin A, Edmunds L, Kennedy LG. Fatigue in ankylosing spondylitis--why is it ignored? J Rheumatol. 1993;20(6):991–995.
   PubMed Web of Science ®Google Scholar
• Hammoudeh M, Zack DJ, Li W, Stewart VM, Koenig AS. Associations between inflammation, nocturnal back pain and fatigue in ankylosing spondylitis and improvements with etanercept therapy. J Int Med Res. 2013;41(4):1150–1159.
   PubMed Web of Science ®Google Scholar
• Kotsis K, Voulgari PV, Drosos AA, Carvalho AF, Hyphantis T. Health-related quality of life in patients with ankylosing spondylitis: a comprehensive review. Expert Rev Pharmacoecon Outcomes Res. 2014;14(6):857–872.
   PubMed Web of Science ®Google Scholar
• Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A. A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol. 1994;21(12):2286–2291.
   PubMed Web of Science ®Google Scholar
• Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the bath ankylosing spondylitis functional index. J Rheumatol. 1994;21(12):2281–2285.
   PubMed Web of Science ®Google Scholar
• Boonen A, van der Heijde D, Landewe R, et al. How do the EQ-5D, SF-6D and the well-being rating scale compare in patients with ankylosing spondylitis? Ann Rheum Dis. 2007;66(6):771–777.
   PubMed Web of Science ®Google Scholar
• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10):1121–1123.
   PubMed Web of Science ®Google Scholar
• Doward LC, Spoorenberg A, Cook SA, et al. Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis. 2003;62(1):20–26.
   PubMed Web of Science ®Google Scholar
• Salaffi F, Carotti M, Gasparini S, Intorcia M, Grassi W. The health-related quality of life in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a comparison with a selected sample of healthy people. Health Qual Life Outcomes. 2009;7:25.
   PubMed Web of Science ®Google Scholar
• Singh H, Arya S, Talapatra P, et al. Assessment of fatigue in rheumatoid arthritis (by functional assessment of chronic illness therapy-fatigue score) and its relation to disease activity and anemia. J Clin Rheumatol. 2014;20(2):87–90.
   PubMed Web of Science ®Google Scholar
• Carneiro C, Chaves M, Verardino G, et al. Evaluation of fatigue and its correlation with quality of life index, anxiety symptoms, depression and activity of disease in patients with psoriatic arthritis. Clin Cosmet Investig Dermatol. 2017;10:155–163.
   PubMed Web of Science ®Google Scholar
• Gudu T, Gossec L. Quality of life in psoriatic arthritis. Expert Rev Clin Immunol. 2018;14(5):405–417.
   PubMed Web of Science ®Google Scholar
• Gudu T, Etcheto A, de Wit M, et al. Fatigue in psoriatic arthritis - a cross-sectional study of 246 patients from 13 countries. Joint Bone Spine. 2016;83(4):439–443.
   PubMed Web of Science ®Google Scholar
• Orbai AM, de Wit M, Mease P, et al. International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials. Ann Rheum Dis. 2017;76(4):673–680.
   PubMed Web of Science ®Google Scholar
• Gossec L, de Wit M, Kiltz U, et al. A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative. Ann Rheum Dis. 2014;73(6):1012–1019.
   PubMed Web of Science ®Google Scholar
• European Union. Olumiant. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/olumiant. Accessed August 11, 2023.
   Google Scholar
• European Union. Xeljanz. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/xeljanz. Accessed August 11, 2023.
   Google Scholar
• European Union. Rinvoq. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/rinvoq. Accessed August 11, 2023.
   Google Scholar
• Smolen JS, Breedveld FC, Burmester GR, et al. Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force. Ann Rheum Dis. 2016;75(1):3–15.
   PubMed Web of Science ®Google Scholar
• Lee EB, Fleischmann R, Hall S, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370(25):2377–2386.
   PubMed Web of Science ®Google Scholar
• Jones G, Sebba A, Gu J, et al. Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study. Ann Rheum Dis. 2010;69(1):88–96.
   PubMed Web of Science ®Google Scholar
• Emery P, Breedveld FC, Hall S, et al. Comparison of methotrexate monotherapy with a combination of methotrexate and etanercept in active, early, moderate to severe rheumatoid arthritis (COMET): a randomised, double-blind, parallel treatment trial. Lancet. 2008;372(9636):375–382.
   PubMed Web of Science ®Google Scholar
• Nash P, Nicholls D. Perceptions of methotrexate use in rheumatoid arthritis by rheumatologists and their patients: an Australian survey study. Int J Rheum Dis. 2013;16(6):652–661.
   PubMed Web of Science ®Google Scholar
• Palmroth M, Kuuliala K, Peltomaa R, et al. Tofacitinib suppresses several JAK-STAT pathways in rheumatoid arthritis in vivo and baseline signaling profile associates with treatment response. Front Immunol. 2021;12:738481.
   PubMed Web of Science ®Google Scholar
• Choy EHS, Calabrese LH. Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis. Rheumatology. 2018;57(11):1885–1895.
   PubMed Web of Science ®Google Scholar
• Li Y, Yuan L, Yang J, et al. Changes in serum cytokines may predict therapeutic efficacy of tofacitinib in rheumatoid arthritis. Mediators Inflamm. 2019;2019:5617431.
   PubMed Web of Science ®Google Scholar
• Wallenstein GV, Kanik KS, Wilkinson B, et al. Effects of the oral Janus kinase inhibitor tofacitinib on patient-reported outcomes in patients with active rheumatoid arthritis: results of two Phase 2 randomised controlled trials. Clin Exp Rheumatol. 2016;34(3):430–442.
   PubMed Web of Science ®Google Scholar
• Strand V, Kremer J, Wallenstein G, et al. Effects of tofacitinib monotherapy on patient-reported outcomes in a randomized Phase 3 study of patients with active rheumatoid arthritis and inadequate responses to DMARDs. Arthritis Res Ther. 2015;17:307.
   PubMed Web of Science ®Google Scholar
• Strand V, van Vollenhoven RF, Lee EB, et al. Tofacitinib or Adalimumab versus placebo: patient-reported outcomes from a phase 3 study of active rheumatoid arthritis. Rheumatology. 2016;55(6):1031–1041.
   PubMed Web of Science ®Google Scholar
• Strand V, Lee EB, Fleischmann R, et al. Tofacitinib versus methotrexate in rheumatoid arthritis: patient-reported outcomes from the randomised phase III ORAL Start trial. RMD Open. 2016;2(2):e000308.
   PubMedGoogle Scholar
• Strand V, Kremer JM, Gruben D, Krishnaswami S, Zwillich SH, Wallenstein GV. Tofacitinib in combination with conventional disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: patient-reported outcomes from a phase iii randomized controlled trial. Arthrit Care Res. 2017;69(4):592–598.
   Web of Science ®Google Scholar
• Strand V, Burmester GR, Zerbini CA, et al. Tofacitinib with methotrexate in third-line treatment of patients with active rheumatoid arthritis: patient-reported outcomes from a phase III trial. Arthrit Care Res. 2015;67(4):475–483.
   Web of Science ®Google Scholar
• Strand V, Mysler E, Moots RJ, et al. Patient-reported outcomes for tofacitinib with and without methotrexate, or Adalimumab with methotrexate, in rheumatoid arthritis: a phase IIIB/IV trial. RMD Open. 2019;5(2):e001040.
   PubMed Web of Science ®Google Scholar
• Mease P, Hall S, FitzGerald O, et al. Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med. 2017;377(16):1537–1550.
   PubMed Web of Science ®Google Scholar
• Gladman D, Rigby W, Azevedo VF, et al. Tofacitinib for psoriatic arthritis in patients with an inadequate response to TNF inhibitors. N Engl J Med. 2017;377(16):1525–1536. doi:10.1056/NEJMoa1615977
   PubMed Web of Science ®Google Scholar
• Coates LC, Bushmakin AG, FitzGerald O, et al. Relationships between psoriatic arthritis composite measures of disease activity with patient-reported outcomes in phase 3 studies of tofacitinib. Arthritis Res Ther. 2021;23(1):94. doi:10.1186/s13075-021-02474-2
   PubMed Web of Science ®Google Scholar
• Overman CL, Kool MB, Da Silva JA, Geenen R. The prevalence of severe fatigue in rheumatic diseases: an international study. Clin Rheumatol. 2016;35(2):409–415. doi:10.1007/s10067-015-3035-6
   PubMed Web of Science ®Google Scholar
• Strand V, de Vlam K, Covarrubias-Cobos JA, et al. Tofacitinib or Adalimumab versus placebo: patient-reported outcomes from OPAL Broaden-a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs. RMD Open. 2019;5(1):e000806. doi:10.1136/rmdopen-2018-000806
   PubMed Web of Science ®Google Scholar
• Strand V, de Vlam K, Covarrubias-Cobos JA, et al. Effect of tofacitinib on patient-reported outcomes in patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors in the Phase III, randomised controlled trial: OPAL Beyond. RMD Open. 2019;5(1):e000808. doi:10.1136/rmdopen-2018-000808
   PubMed Web of Science ®Google Scholar
• van der Heijde D, Deodhar A, Wei JC, et al. Tofacitinib in patients with ankylosing spondylitis: a Phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2017;76(8):1340–1347. doi:10.1136/annrheumdis-2016-210322
   PubMed Web of Science ®Google Scholar
• Navarro-Compan V, Wei JC, Van den Bosch F, et al. Effect of tofacitinib on pain, fatigue, health-related quality of life and work productivity in patients with active ankylosing spondylitis: results from a phase III, randomised, double-blind, placebo-controlled trial. RMD Open. 2022;8(2):e002253. doi:10.1136/rmdopen-2022-002253
   PubMed Web of Science ®Google Scholar
• Ruperto N, Brunner HI, Synoverska O, et al. Tofacitinib in juvenile idiopathic arthritis: a double-blind, placebo-controlled, withdrawal phase 3 randomised trial. Lancet. 2021;398(10315):1984–1996. doi:10.1016/S0140-6736(21)01255-1
   PubMed Web of Science ®Google Scholar
• McInnes IB, Byers NL, Higgs RE, et al. Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations. Arthritis Res Ther. 2019;21(1):183. doi:10.1186/s13075-019-1964-1
   PubMed Web of Science ®Google Scholar
• Weston S, Macdonald JL, Williams LM, et al. The JAK inhibitor baricitinib inhibits oncostatin M induction of proinflammatory mediators in ex-vivo synovial derived cells. Clin Exp Rheumatol. 2021;40:1620–1628. doi:10.55563/clinexprheumatol/cfsajk
   PubMed Web of Science ®Google Scholar
• Choy EHS, Miceli-Richard C, Gonzalez-Gay MA, et al. The effect of JAK1/JAK2 inhibition in rheumatoid arthritis: efficacy and safety of baricitinib. Clin Exp Rheumatol. 2019;37(4):694–704.
   PubMed Web of Science ®Google Scholar
• Schiff M, Takeuchi T, Fleischmann R, et al. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther. 2017;19(1):208. doi:10.1186/s13075-017-1410-1
   PubMedGoogle Scholar
• Taylor PC, Alten R, Alvaro Gracia JM, et al. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022;8(1):e001994. doi:10.1136/rmdopen-2021-001994
   PubMed Web of Science ®Google Scholar
• Michaud K, Pope JE, Emery P, et al. Relative Impact of pain and fatigue on work productivity in patients with rheumatoid arthritis from the RA-BEAM baricitinib trial. Rheumatol Therap. 2019;6(3):409–419. doi:10.1007/s40744-019-0164-4
   PubMed Web of Science ®Google Scholar
• Keystone EC, Taylor PC, Tanaka Y, et al. Patient-reported outcomes from a phase 3 study of baricitinib versus placebo or Adalimumab in rheumatoid arthritis: secondary analyses from the RA-BEAM study. Ann Rheum Dis. 2017;76(11):1853–1861. doi:10.1136/annrheumdis-2017-211259
   PubMed Web of Science ®Google Scholar
• Genovese MC, Kremer J, Zamani O, et al. Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med. 2016;374(13):1243–1252. doi:10.1056/NEJMoa1507247
   PubMed Web of Science ®Google Scholar
• Smolen JS, Kremer JM, Gaich CL, et al. Patient-reported outcomes from a randomised phase III study of baricitinib in patients with rheumatoid arthritis and an inadequate response to biological agents (RA-BEACON). Ann Rheum Dis. 2017;76(4):694–700. doi:10.1136/annrheumdis-2016-209821
   PubMed Web of Science ®Google Scholar
• Fautrel B, Wu J, Wang D, Haladyj E, van de Laar M, Takeuchi T. Relative impact of pain and disease activity on improvements in fatigue: results from 2 baricitinib phase 3 clinical trials. J Clin Rheumatol. 2022;2022:1.
   Google Scholar
• Parmentier JM, Voss J, Graff C, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2018;2:23. doi:10.1186/s41927-018-0031-x
   PubMedGoogle Scholar
• Strand V, Pope J, Tundia N, et al. Upadacitinib improves patient-reported outcomes in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying antirheumatic drugs: results from SELECT-NEXT. Arthritis Res Ther. 2019;21(1):272. doi:10.1186/s13075-019-2037-1
   PubMed Web of Science ®Google Scholar
• Strand V, Tundia N, Bergman M, et al. Upadacitinib improves patient-reported outcomes vs placebo or Adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Rheumatology. 2021;60(12):5583–5594. doi:10.1093/rheumatology/keab158
   PubMed Web of Science ®Google Scholar
• McInnes IB, Ostor AJK, Mease PJ, et al. Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: post hoc analysis of three randomised clinical trials. RMD Open. 2022;8(1):e002049. doi:10.1136/rmdopen-2021-002049
   PubMed Web of Science ®Google Scholar
• Deodhar A, van der Heijde D, Sieper J, et al. Safety and efficacy of upadacitinib in patients with active ankylosing spondylitis and an inadequate response to nonsteroidal antiinflammatory drug therapy: one-year results of a double-blind, placebo-controlled study and open-label extension. Arthrit Rheumatol. 2022;74(1):70–80. doi:10.1002/art.41911
   PubMed Web of Science ®Google Scholar
• van der Heijde D, Deodhar A, Maksymowych WP, et al. Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension. RMD Open. 2022;8(2):e002280. doi:10.1136/rmdopen-2022-002280
   PubMed Web of Science ®Google Scholar
• European Union. Jyseleca. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/jyseleca. Accessed August 11, 2023.
   Google Scholar
• Namour F, Anderson K, Nelson C, Tasset C. Filgotinib: a clinical pharmacology review. Clin Pharmacokinet. 2022;61:819–832. doi:10.1007/s40262-022-01129-y
   PubMed Web of Science ®Google Scholar
• Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021;80(7):865–875. doi:10.1136/annrheumdis-2020-219012
   PubMed Web of Science ®Google Scholar
• Dowty ME, Lin TH, Jesson MI, et al. Janus kinase inhibitors for the treatment of rheumatoid arthritis demonstrate similar profiles of in vitro cytokine receptor inhibition. Pharmacol Res Perspect. 2019;7(6):e00537. doi:10.1002/prp2.537
   PubMed Web of Science ®Google Scholar
• Bingham CO 3rd, Walker D, Nash P, et al. The impact of filgotinib on patient-reported outcomes and health-related quality of life for patients with active rheumatoid arthritis: a post hoc analysis of Phase 3 studies. Arthritis Res Ther. 2022;24(1):11. doi:10.1186/s13075-021-02677-7
   PubMedGoogle Scholar
• Huarte E, Peel MT, Verbist K, et al. Ruxolitinib, a JAK1/2 Inhibitor, ameliorates cytokine storm in experimental models of hyperinflammation syndrome. Front Pharmacol. 2021;12:650295. doi:10.3389/fphar.2021.650295
   PubMed Web of Science ®Google Scholar
• Bader-Meunier B, Hadchouel A, Berteloot L, et al. Effectiveness and safety of ruxolitinib for the treatment of refractory systemic idiopathic juvenile arthritis like associated with interstitial lung disease: a case report. Ann Rheum Dis. 2022;81(2):e20. doi:10.1136/annrheumdis-2020-216983
   PubMed Web of Science ®Google Scholar
• Jain P, Keating M, Renner S, et al. Ruxolitinib for symptom control in patients with chronic lymphocytic leukaemia: a single-group, phase 2 trial. Lancet Haematol. 2017;4(2):e67–e74. doi:10.1016/S2352-3026(16)30194-6
   PubMed Web of Science ®Google Scholar
• Hardwick RN, Brassil P, Badagnani I, et al. Gut-selective design of orally administered izencitinib (TD-1473) limits systemic exposure and effects of janus kinase inhibition in nonclinical species. Toxicol Sci. 2022;186(2):323–337. doi:10.1093/toxsci/kfac002
   PubMed Web of Science ®Google Scholar
• Toth L, Juhasz MF, Szabo L, et al. Janus kinase inhibitors improve disease activity and patient-reported outcomes in rheumatoid arthritis: a systematic review and meta-analysis of 24,135 patients. Int J Mol Sci. 2022;23(3):1246. doi:10.3390/ijms23031246
   PubMed Web of Science ®Google Scholar
• Odriozola ICC, Barnetche T, Richez C, Bannwarth B, Schaeverbeke T Is there a specific effect of jak-inhibitors on pain and fatigue in rheumatoid arthritis? Available from: https://acrabstracts.org/abstract/is-there-a-specific-effect-of-jak-inhibitors-on-pain-and-fatigue-in-rheumatoid-arthritis/. Accessed August 11, 2023.
   Google Scholar
• Taylor PC, Keystone EC, van der Heijde D, et al. Baricitinib versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2017;376(7):652–662. doi:10.1056/NEJMoa1608345
   PubMed Web of Science ®Google Scholar
• Fleischmann R, Pangan AL, Song IH, et al. Upadacitinib versus placebo or adalimumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase III, double-blind, randomized controlled trial. Arthrit Rheumatol. 2019;71(11):1788–1800. doi:10.1002/art.41032
   PubMed Web of Science ®Google Scholar
• Fleischmann R, Mysler E, Hall S, et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and Adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet. 2017;390(10093):457–468. doi:10.1016/S0140-6736(17)31618-5
   PubMed Web of Science ®Google Scholar
• Combe B, Kivitz A, Tanaka Y, et al. Filgotinib versus placebo or Adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial. Ann Rheum Dis. 2021;80(7):848–858. doi:10.1136/annrheumdis-2020-219214
   PubMed Web of Science ®Google Scholar
• EMA confirms measures to minimise risk of serious side effects with Janus kinase inhibitors for chronic inflammatory disorders. Available from: https://www.ema.europa.eu/en/news/ema-confirms-measures-minimise-risk-serious-side-effects-janus-kinase-inhibitors-chronic. Accessed August 11, 2023.
   Google Scholar