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Strategies to Improve Outcomes in Psoriatic Arthritis

  • Psoriatic Arthritis (JU Scher, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The therapeutic response to biologic agents in psoriasis is significantly higher than observed in psoriatic arthritis (PsA). In this review, specific actions to improve treatment outcomes in PsA are discussed.

Recent Findings

Increased understanding of disease pathogenesis derived from improved preclinical models and advances in cell-based and molecular technologies provide new tools to identify therapeutic targets. In addition to the important contributions of metabolic comorbidities, chronic pain and the lack of a diagnostic biomarker signal the need for new strategies to improve outcomes. Potential strategies include the following: (1) discover a novel pathway or cellular subset, (2) apply stratification biomarkers to individualize therapy, (3) preclinical intervention, (4) combination therapy, (5) lifestyle modification, (6) address chronic pain and fatigue, and (7) multidisciplinary care.

Summary

The future holds great promise for enhanced treatment responses in PsA based on improved understanding of individual variation in disease pathophysiology coupled with comprehensive and integrated treatment programs.

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References

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  1. Moll JM, Wright V. Psoriatic arthritis. Seminars in Arthritis and Rheumatism. 1973;3(1):55–78.

    CAS  PubMed  Google Scholar 

  2. Moll JM, Haslock I, Macrae IF, Wright V. Associations between ankylosing spondylitis, psoriatic arthritis, Reiter’s disease, the intestinal arthropathies, and Behcet’s syndrome. Medicine. 1974;53(5):343–64.

    CAS  PubMed  Google Scholar 

  3. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med. 2017;376(10):957–70.

    PubMed  Google Scholar 

  4. Kavanaugh AF, Ritchlin CT, Committee GTG. Systematic review of treatments for psoriatic arthritis: an evidence based approach and basis for treatment guidelines. The Journal of Rheumatology. 2006;33(7):1417–21.

    PubMed  Google Scholar 

  5. Coates LC, FitzGerald O, Merola JF, Smolen J, van Mens LJJ, Bertheussen H, et al. Group for research and assessment of psoriasis and psoriatic arthritis/outcome measures in rheumatology consensus-based recommendations and research agenda for use of composite measures and treatment targets in psoriatic arthritis. Arthritis & Rheumatology. 2018;70(3):345–55.

    Google Scholar 

  6. Raychaudhuri SP, Wilken R, Sukhov AC, Raychaudhuri SK, Maverakis E. Management of psoriatic arthritis: early diagnosis, monitoring of disease severity and cutting edge therapies. J Autoimmun. 2017;76:21–37.

    PubMed  Google Scholar 

  7. Mease PJ, Coates LC. Considerations for the definition of remission criteria in psoriatic arthritis. Seminars in arthritis and rheumatism. 2018;47(6):786–96 Thoughtful discussion on the application of composiite measures to define remission in PsA.

    PubMed  Google Scholar 

  8. Baeten D, Ostergaard M, Wei JC, Sieper J, Jarvinen P, Tam LS, et al. Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study. Annals of the Rheumatic Diseases. 2018;77(9):1295–302 The antibody to IL-23 was ineffective in treating ankylosing spondylitis. This finding was unexpected based on the preclinical reports that demonstrated an etiologic role of IL-23 in axial inflammation.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Araujo EG, Englbrech M, Hoepken S, Finzel S, Hueber AJ, Rech J, et al. Ustekinumab is superior to TNF inhibitor treatment in resolving enthesitis in Psa patients with active enthesitis- results from the enthesial clearance in psoriatic arthritis study [abstract]. Arthritis Rheumatol. 2017;69(suppl 10).

  10. Conrad C, Gilliet M. Psoriasis: from pathogenesis to targeted therapies. Clinical Reviews in Allergy & immunology. 2018;54(1):102–13.

    CAS  Google Scholar 

  11. McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity. 2019;50(4):892–906 Comprehensive and timely review of the structure and function of the IL-17 molecules and the central importance of this family in immune-mediated disorders including psoriasis and PsA.

    CAS  PubMed  Google Scholar 

  12. Donlin LT, Rao DA, Wei K, Slowikowski K, McGeachy MJ, Turner JD, et al. Methods for high-dimensonal analysis of cells dissociated from cyropreserved synovial tissue. Arthritis Research & Therapy. 2018;20(1):139.

    Google Scholar 

  13. Tang F, Barbacioru C, Nordman E, Li B, Xu N, Bashkirov VI, et al. RNA-Seq analysis to capture the transcriptome landscape of a single cell. Nat Protoc. 2010;5(3):516–35.

    CAS  PubMed  Google Scholar 

  14. Stadhouders R, Lubberts E, Hendriks RW. A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun. 2018;87:1–15.

    CAS  PubMed  Google Scholar 

  15. Stephenson W, Donlin LT, Butler A, Rozo C, Bracken B, Rashidfarrokhi A, et al. Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation. Nat Commun. 2018;9(1):791 This report demonstrated that scRNA-seq can be performed with a low-cost microfluidic instrument which was applied to the analysis of cell populations in rheumatoid synovium.

    PubMed  PubMed Central  Google Scholar 

  16. Mimitou EP, Cheng A, Montalbano A, Hao S, Stoeckius M, Legut M, et al. Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells. Nat Methods. 2019;16(5):409–12.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Croft AP, Campos J, Jansen K, Turner JD, Marshall J, Attar M, et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature. 2019;570(7760):246–51 This scRNA-seq analysis of rheumatoid synovium identified 5 fibroblastoid populations located in different regions of the synovial membrane. Specific subsets expressed genes associated with inflammation or tissue degradation.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Matos TR, O’Malley JT, Lowry EL, Hamm D, Kirsch IR, Robins HS, et al. Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing alphabeta T cell clones. The Journal of Clinical Investigation. 2017;127(11):4031–41.

    PubMed  PubMed Central  Google Scholar 

  19. Nguyen CT, Maverakis E, Eberl M, Adamopoulos IE. gammadelta T cells in rheumatic diseases: from fundamental mechanisms to autoimmunity. Semin Immunopathol. 2019.

  20. Culemann S, Gruneboom A, Nicolas-Avila JA, Weidner D, Lammle KF, Rothe T, et al. Locally renewing resident synovial macrophages provide a protective barrier for the joint. Nature. 2019;572(7771):670–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542(7640):177–85 Elegant discussion of the interaction between metabolic and inflammatory pathways that is of particular relevance in PsA.

    CAS  PubMed  Google Scholar 

  22. Aterido A, Canete JD, Tornero J, Ferrandiz C, Pinto JA, Gratacos J, et al. Genetic variation at the glycosaminoglycan metabolism pathway contributes to the risk of psoriatic arthritis but not psoriasis. Annals of the Rheumatic diseases. 2019;78(3).

  23. Pietrzak A, Chabros P, Grywalska E, Kicinski P, Pietrzak-Franciszkiewicz K, Krasowska D, et al. Serum lipid metabolism in psoriasis and psoriatic arthritis - an update. Arch Med Sci. 2019;15(2):369–75.

    CAS  PubMed  Google Scholar 

  24. McGarry T, Orr C, Wade S, Biniecka M, Wade S, Gallagher L, et al. JAK/STAT Blockade alters synovial bioenergetics, mitochondrial function, and proinflammatory mediators in rheumatoid arthritis. Arthritis & Rheumatology. 2018;70(12):1959–70.

    CAS  Google Scholar 

  25. Orange DE, Agius P, DiCarlo EF, Robine N, Geiger H, Szymonifka J, et al. Identification of three rheumatoid arthritis disease subtypes by machine learning integration of synovial histologic features and rna sequencing data. Arthritis & Rheumatology. 2018;70(5):690–701.

    CAS  Google Scholar 

  26. Miyagawa I, Nakayamada S, Nakano K, Kubo S, Iwata S, Miyazaki Y, et al. Precision medicine using different biological DMARDs based on characteristic phenotypes of peripheral T helper cells in psoriatic arthritis. Rheumatology. 2019;58(2):336–44.

    PubMed  Google Scholar 

  27. Al-Mossawi H, Coates LC. Personalized medicine - a new reality in psoriatic arthritis? Nature Reviews Rheumatology. 2018;14(8):449–51.

    CAS  PubMed  Google Scholar 

  28. Palit S, Heuser C, de Almeida GP, Theis FJ, Zielinski CE. Meeting the challenges of high-dimensional single-cell data analysis in immunology. Front Immunol. 2019;10:1515.

    PubMed  PubMed Central  Google Scholar 

  29. Tillett W, Charlton R, Nightingale A, Snowball J, Green A, Smith C, et al. Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort. Rheumatology. 2017;56(12):2109–13.

    PubMed  Google Scholar 

  30. Eder L, Polachek A, Rosen CF, Chandran V, Cook R, Gladman DD. The development of psoriatic arthritis in patients with psoriasis is preceded by a period of nonspecific musculoskeletal symptoms: a prospective cohort study. Arthritis & Eheumatology. 2017;69(3, 622):–9 Important report that documented early clinical symptoms of PsA in a large longitudinal psoriasis cohort.

  31. Ogdie A, Gelfand JM. Clinical risk factors for the development of psoriatic arthritis among patients with psoriasis: a review of available evidence. Current Rheumatology Reports. 2015;17(10):64.

    PubMed  PubMed Central  Google Scholar 

  32. Faustini F, Simon D, Oliveira I, Kleyer A, Haschka J, Englbrecht M, et al. Subclinical joint inflammation in patients with psoriasis without concomitant psoriatic arthritis: a cross-sectional and longitudinal analysis. Annals of the Rheumatic Diseases. 2016.

  33. Finzel S, Ohrndorf S, Englbrecht M, Stach C, Messerschmidt J, Schett G, et al. A detailed comparative study of high-resolution ultrasound and micro-computed tomography for detection of arthritic bone erosions. Arthritis and Rheumatism. 2011;63(5):1231–6.

    PubMed  Google Scholar 

  34. Gisondi P, Tinazzi I, El-Dalati G, Gallo M, Biasi D, Barbara LM, et al. Lower limb enthesopathy in patients with psoriasis without clinical signs of arthropathy: a hospital-based case-control study. Annals of the Rheumatic Diseases. 2008;67(1):26–30.

    CAS  PubMed  Google Scholar 

  35. Namey TC, Rosenthall L. Periarticular uptake of 99mtechnetium diphosphonate in psoriatics: correlation with cutaneous activity. Arthritis and Rheumatism. 1976;19(3):607–12.

    CAS  PubMed  Google Scholar 

  36. Simon D, Faustini F, Kleyer A, Haschka J, Englbrecht M, Kraus S, et al. Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis. Annals of the Rheumatic Diseases. 2016;75(4):660–6.

    CAS  PubMed  Google Scholar 

  37. Savage L, Goodfield M, Horton L, Watad A, Hensor E, Emery P, et al. Regression of peripheral subclinical enthesopathy in therapy-naive patients treated with ustekinumab for moderate-to-severe chronic plaque psoriasis: a fifty-two-week, prospective, open-label feasibility study. Arthritis & Rheumatology. 2019;71(4):626–31.

    CAS  Google Scholar 

  38. Scher JU, Ogdie A, Merola JF, Ritchlin C. Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nature reviews Rheumatology. 2019;15(3):153–66 Comprehensive review of the risk factors and pathophysiologic events associated with the transition from psoriasis to PsA.

    PubMed  Google Scholar 

  39. Mease PJ, Gladman DD, Coller DH, Ritchlin CT, Helliwell PS, Kricorian G, et al. Monotherapy or in combination for psoriatic arthritis: primary results from a randomized, controlled phase III trial. Arthritis & rheumatology. 2019;71(7):1112-24. First clinical trial to document that combination therapy with etanercept and methotrexate was not more effective than etanercept alone for treatment of PsA. Methotrexate monotherapy, however, was shown to be effective for all domains.

  40. van der Heijde D, Klareskog L, Rodriguez-Valverde V, Codreanu C, Bolosiu H, Melo-Gomes J, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis and Rheumatism. 2006;54(4):1063–74.

    PubMed  Google Scholar 

  41. Genovese MC, Cohen S, Moreland L, Lium D, Robbins S, Newmark R, et al. Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. Arthritis and Rheumatism. 2004;50(5):1412–9.

    CAS  PubMed  Google Scholar 

  42. Genovese MC, Weinblatt ME, Aelion JA, Mansikka HT, Peloso PM, Chen K, et al. ABT-122, a bispecific dual variable domain immunoglobulin targeting tumor necrosis factor and interleukin-17A, in patients with rheumatoid arthritis with an inadequate response to methotrexate: a randomized, double-blind study. Arthritis & Rheumatology. 2018;70(11):1710–20.

    CAS  Google Scholar 

  43. Mease PJ, Genovese MC, Weinblatt ME, Peloso PM, Chen K, Othman AA, et al. Phase II study of ABT-122, a tumor necrosis factor- and interleukin-17A-targeted dual variable domain immunoglobulin, in patients with psoriatic arthritis with an inadequate response to methotrexate. Arthritis & Rheumatology. 2018;70(11):1778–89 The dual variable domain immunoglobulin (anti-IL-17 and anti-TNF) was not more effective than adalimumab alone but adverse events were not higher in the patients treated with the antibody construct.

    CAS  Google Scholar 

  44. Ogdie A, Schwartzman S, Husni ME. Recognizing and managing comorbidities in psoriatic arthritis. Current opinion in Rheumatology. 2015;27(2):118–26.

    PubMed  Google Scholar 

  45. Hojgaard P, Glintborg B, Kristensen LE, Gudbjornsson B, Love TJ, Dreyer L. The influence of obesity on response to tumour necrosis factor-alpha inhibitors in psoriatic arthritis: results from the DANBIO and ICEBIO registries. Rheumatology. 2016;55(12):2191–9.

    PubMed  Google Scholar 

  46. Di Minno MN, Peluso R, Iervolino S, Russolillo A, Lupoli R, Scarpa R, et al. Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor alpha blockers. Annals of the Rheumatic Diseases. 2014;73(6):1157–62.

    PubMed  Google Scholar 

  47. Klingberg E, Bilberg A, Bjorkman S, Hedberg M, Jacobsson L, Forsblad-d’Elia H, et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis research & therapy. 2019;21(1):17 Marked caloric restriction followed by a supportive dietary counseling was associated with a high degree of weight loss and significant improvement in a wide range of clinical parameters in PsA.

    Google Scholar 

  48. Liu R, Hong J, Xu X, Feng Q, Zhang D, Gu Y, et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nature Medicine. 2017;23(7):859–68.

    CAS  PubMed  Google Scholar 

  49. Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, et al. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis & Rheumatology. 2015;67(1):128–39.

    CAS  Google Scholar 

  50. Ansaldo E, Slayden LC, Ching KL, Koch MA, Wolf NK, Plichta DR, et al. Akkermansia muciniphila induces intestinal adaptive immune responses during homeostasis. Science. 2019;364(6446):1179–84 Interesting report that discusses the impact of this bacterial species on the gut immune reponse.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nature Medicine. 2019;25(7):1096–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Benatti FB, Pedersen BK. Exercise as an anti-inflammatory therapy for rheumatic diseases-myokine regulation. Nature reviews. Rheumatology. 2015;11(2):86–97.

    CAS  PubMed  Google Scholar 

  53. Bidonde J, Busch AJ, Schachter CL, Webber SC, Musselman KE, Overend TJ, et al. Mixed exercise training for adults with fibromyalgia. Cochrane Database Syst Rev. 2019;5:CD013340.

    PubMed  Google Scholar 

  54. Husni ME, Merola JF, Davin S. The psychosocial burden of psoriatic arthritis. Seminars in Arthritis and Rheumatism. 2017;47(3):351–60 Comprehensive and thoughtful discussion of the psychosocial challenges prevalent in PsA.

    PubMed  Google Scholar 

  55. Rifbjerg-Madsen S, Christensen AW, Christensen R, Hetland ML, Bliddal H, Kristensen LE, et al. Pain and pain mechanisms in patients with inflammatory arthritis: a Danish nationwide cross-sectional DANBIO registry survey. PloS one. 2017;12(7):e0180014.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Lage-Hansen PR, Chrysidis S, Lage-Hansen M, Hougaard A, Ejstrup L, Amris K. Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy: a cross-sectional study. Scandinavian Journal of Rheumatology. 2016;45(1):45–8.

    CAS  PubMed  Google Scholar 

  57. Hojgaard P, Ellegaard K, Nielsen SM, Christensen R, Guldberg-Moller J, Ballegaard C, et al. Pain mechanisms and ultrasonic inflammatory activity as prognostic factors in patients with psoriatic arthritis: a prospective cohort study. Arthritis Care & Research. 2019;71(6):798–810.

    CAS  Google Scholar 

  58. Skougaard M, Jorgensen TS, Rifbjerg-Madsen S, Coates LC, Egeberg A, Amris K, et al. In psoriatic arthritis fatigue is driven by inflammation, disease duration, and chronic pain: an observational DANBIO registry study. The Journal of Rheumatology. 2019.

  59. Thomsen RS, Nilsen TIL, Haugeberg G, Bye A, Kavanaugh A, Hoff M. Impact of high-intensity interval training on disease activity and disease in patients with psoriatic arthritis: a randomized controlled trial. Arthritis Care & Research. 2019;71(4):530–7 High-intensity interval training was associated with decreased level of fatigue in PsA.

    Google Scholar 

  60. Okhovat JP, Ogdie A, Reddy SM, Rosen CF, Scher JU, Merola JF. Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network Consortium (PPACMAN) Survey: benefits and challenges of combined rheumatology-dermatology clinics. The Journal of Rheumatology. 2017;44(5):693–4.

    PubMed  Google Scholar 

  61. Soleymani T, Reddy SM, Cohen JM, Neimann AL. Early recognition and treatment heralds optimal outcomes: the benefits of combined rheumatology-dermatology clinics and integrative care of psoriasis and psoriatic arthritis patients. Current rheumatology reports. 2017;20(1):1 Excellent discussion of multidisciplinary care in psoriatic disease and potential impact on patient outcomes.

    CAS  PubMed  Google Scholar 

  62. Queiro R, Coto P, Rodriguez J, Notario J, Navio Marco T, de la Cueva P, et al. Multidisciplinary care models for patients with psoriatic arthritis. Reumatol Clin. 2017;13(2):85–90.

    PubMed  Google Scholar 

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Ritchlin, C., Scher, J.U. Strategies to Improve Outcomes in Psoriatic Arthritis. Curr Rheumatol Rep 21, 72 (2019). https://doi.org/10.1007/s11926-019-0876-z

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