ALTERAZIONI GENERALI E LEGATE

AL SITO DI INIEZIONE

Vertigini, eritema e/o prurito, emorragia, dolore, edema

DISTURBI DEL METABOLISMO Iperlipemia, ipokaliemia, iperuricemia, iperglicemia, ipocalcemia DISTURBI PSICHIATRICI Disturbi dell’umore, ansia, insonnia

NEOPLASIE Carcinoma basocellulare e a cellule squamose. Rari tumore mammella,

Tabella III: dati demografici e clinici dei pazienti studiati

M:F (N:N) 44:39

Età media all’esordio della malattia (anni; N±DS) 40.6±13.2 Durata media di malattia (mesi; N±DS) 144.3±74,9 Numero di DMARDs usati prima dell’anti-TNFa (N±DS) 2.2±1 Monoterapia con anti-TNFa:terapia di combinazione con anti-TNFa

(N:N) 52:31

DMARDs usati in terapia di combinazione (N) methotrexate leflunomide ciclosporina-A sulfosalazina idrossiclorochina 19 5 2 2 3

Tabella IV: cause di sospensione della terapia con adalimumab

Numero di pazienti che hanno sospeso la terapia con adalimumab 24

Cause di interruzione nei singoli pazienti

ridotta efficacia sulla psoriasi cutanea

ridotta efficacia su psoriasi cutanea e artrite psoriasica ridotta efficacia sull’artrite psoriasica

ridotta efficacia sull’artrite psoriasica ed edema al volto decisione del paziente

ipercolesterolemia rettorragia

anemia

pleuropericardite

pleurite con tosse e febbre tosse produttiva

polmonite diverticolite

aumento transaminasi

alterazione del visus e parestesie gravidanza durata della terapia in mesi 34 4 e 74 6, 15, 16, 28, 30, 38, 50 1 26 24 1 12 4 76 3 3 5 4, 8 7 96

Tabella V: persistenza in terapia Persistenza (mesi) Gruppo generale (%; N) Pazienti in monoterapia (%; N) Pazienti in terapia di combinazione (%; N) 12 mesi 86,8%; 76 86,5%; 50 88,9%; 26 24 mesi 82,3%; 68 79,2%; 47 85,7%; 21 36 mesi 67,8%; 59 68,3%; 41 66,7%; 18

BIBLIOGRAFIA

1) Wright V, Moll JMH. Psoriatic arthritis in seronegative polyarthritis. Amsterdam: North Holland Publishing; 1976:169-223.

2) Mercieca C, Landewè R, Borg A. Spondyloarthritis: pathogenesis, clinical aspects and diagnosis. Eular on-line course on rheumatic diseases 2012 – module n°6.

3) Ritchlin C. Psoriatic Arthritis: pathology and and pathogenesis. In: Klippel JH, Stone JH, Crofford LJ, et al. Primer on the Rheumatic Diseases, XIII ed. New York: Springer editore, 2008; cap.8:178-84.

4) Salvarani C, Lo Scocco G, Macchioni P et al. Prevalence of psoriatic arthritis in Italian psoriatic patients. J Rheumatol 1995;22:1499-503.

5) Gelfand JM, Gladman DD, Mease PJ et al. Epidemiology of psoriatic arthritis in the population of the United States. J Am Acad Dermatol 2005;53:573-7.

6) Punzi L. Artrite Psoriasica. In: Todesco S, Gambari PF: Malattie Reumatiche, III ed. Milano: McGraw-Hill editore 2002; cap 6:173-80.

7) Rahman P, Elder JT. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64(suppl.2):37-41.

8) Mease PJ. Tumour necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis 2002;61:298–304.

9) Langevitz P, Buskila D, Gladman DD. Psoriatic arthritis precipitated by physical trauma. J Rheumatol 1990;17:695-7.

10) Wang O, Vasey FB, Mahfood JP, et al. V2 regions of 16S ribosomal RNA used an a molecular marker for the species identification of streptococci in peripheral blood and synovial fluid from patients with psoriatic arthritis. Arthritis Rheum 1999;42:2055-9.

11) Travers JB, Hamid QA, Norris DA et al. Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis. J Clin Invest 1999;104:1181-9.

12) McGonagle D, Conaghan PG, Emery P. Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum 1999;42:1080-6.

13) Pitzalis C, Cauli A, Pipitone N et al. Cutaneous Lymphocyte Antigen- positive T Lymphocytes Preferentially Migrate to the Skin but not to the Joint in Psoriatic Arthritis. Arthritis Rheum 1996;39:137-45.

14) Ritchlin C, Haas-Smith SA, Hicks D, Cappuccio J, Osterland CK, Looney RJ. Patterns of cytokine production in psoriatic synovium. J Rheumatol 1998;25:1544-52.

15) Veale D, Yanni G, Rogers S, Barnes L, Bresnihan B, Fitzgerald O. Reduced synovial membrane macrophage numbers, ELAM-1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis. Arthritis Rheum 1993;36:893-900.

16) Veale DJ, Barnes L, Rogers S, Fitzgerald O. Immunohistochemical markers for arthritis in psoriasis. Ann Rheum Dis 1994;53:450-4.

17) Costello P, Fitzgerald O. Disease mechanism in psoriasis and psoriatic arthritis. Curr Rheumatol Rep 2001;3:419-27.

18) Tassiulas I, Duncan SR, Centola M, Theofilopoulos AN, Boumpas DT. Clonal characteristics of T cell infiltrates in skin and synovium of patients with psoriatic arthritis. Hum Immunol 1999; 60:479-91.

19) Costello PJ, Winchester RJ, Curran SA et al. Psoriatic arthritis joint fluids are characterized by CD8 and CD4 T cell clonal expansions appear antigen driven. J Immunol 2001;166:2878-86.

20) Danning CL, Illei GG, Hitchon C, Greer MR, Boumpas DT, McInnes IB. Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and of patients with psoriatic arthritis. Arthritis Rheum 2000;43:1244-1256.

21) Wright V, Moll JMH. Psoriatic arthritis in seronegative polyarthritis. Amsterdam: North Holland Publishing. 1976:169-223.

22) Ballistone MJ. Manaster BJ, Reda DJ et al. The prevalence of sacroileitis in psoriatic arthritis: new prospectives from a large, multicenter cohort. Skeletal Radiol 1999;28:196-01.

23) Cantini F, Salvarani C, Olivieri I et al. Distal extremity swelling with pitting edema in psoriatic arthiritis: a case-control study. Clin Exp Rheumatol 2001;19:291-6.

24) Olivieri I, Salvarani C, Cantini F et al. Fast spin echo-T2-weighted sequences with fat saturation in dactylitis of spondylarthritis. No evidence of entheseal involvement of the flexor digitorum tendons. Arthritis Rheum 2002;46:2964-7.

25) Brockbank J, Stein M, Schentag CT et al. Characteristics of dactylitis in psoriatic arthritis (PsA). Ann Rheum Dis 2005;62:188-90.

26) D'Agostino MA, Palazzi C, Olivieri I. Entheseal involvement. Clin Exp Rheumatol 2009;27(4 Suppl 55):S50-5.

27) Elkayam O, Ophir J, Yaron M et al. Psoriatic arthritis: interrelationship between skin and joint manifestation related to onset, course and distribution. Clin Rheumatol 2000;19:301-5.

28) Williamson L, Docketry JL, Dalbeth N et al. Gastrointestinal disease and psoriatic arthritis. J Rheumatol 2004;31:1469-70.

29) Gladman DD, Anhorn KB, Schachter RK et al. HLA antigens in psoriatic arthritis. J Rheumatol 1986;13:586-92.

30) Scarpa R, Manguso F, D’Arenzio A et al. Microscopic inflammatory changes in colon of patients with both active psoriasis and psoriatic arthritis without bowel symptoms. J Rheumatol 2000;27:1241-6.

31) Tobin AM, Veale DJ, Fitzgerald O et al. Cardiovascular Disease and Risk Factors in Patients with Psoriasis and Psoriatic Arthritis. J Rheumatol 2010;37:1386-94.

32) Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 2006;54:2665-73.

33) Abbas AK, Lichtman AH, Pober JS. Cellular and molecular immunology; IV ed. Philadelphia: W.B. Saunders Company 2000; cap 11:251-257.

34) Krueger G, Callis K. Potential of Tumor Necrosis Factor Inhibitors in Psoriasis and Psoriatic Arthritis. Arch Dermatol 2004;140:218-221.

35) Sarzi-Puttini P, Atzeni F. New Biological Treatments for Psoriatic Arthritis. IMAJ 2014;16: 643-45.

36) Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and psoriatic arthritis. J Autoimmun 2010;34:314-21.

37) Gatto B. Biologics targeted at TNF: design, production and challenges. Reumatismo 2006;58:94-103.

38) Mease P. TNF-alpha therapy in psoriatic arthritis and psoriasis. Ann Rheum Dis 2004;63:755–758.

39) Bencsáth M, Blaskovits A, Borvendég J. Biomolecular Cytokine Therapy. Pathology Oncology Research 2003;9:24-9.

40) Radstake TR, Svenson M, Eijsbouts AM et al. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis. Ann Rheum Dis 2009;68:1739-45.

41) Wolbink GJ, Vis M, Lems W et al. Development of antiinfliximab antibodies and relationship to clinical response in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:711–5.

42) de Vries MK, Wolbink GJ, Stapel SO et al. Decreased clinical response to infliximab in ankylosing spondylitis is correlated with anti-infliximab formation. Ann Rheum Dis 2007;66:1252–4.

43) Aikawa NE, de Carvalho JF, Almeida Silva CA, Bonfa E. Immunogenicity of anti-TNF agents in autoimmune diseases. Clinic Rev Allerg Immunol 2010;38:82-9.

44) Zisapel M, Zisman D, Madar-Balakirski N et al. Prevalence of TNF-α Blocker Immunogenicity in Psoriatic Arthritis. J Rheumatol 2015;42:73-8. 45) Bartelds GM, Wolbink GJ, Stapel S et al. High levels of human anti- human antibodies to adalimumab in a patient not responding to adalimumab treatment. Ann Rheum Dis 2006;65:1249-50.

46) Fiocco U, Bombardieri S. Differences in pharmacology of tumor necrosis

47) Wick MC, Ernestam S, Lindblad S, Bratt J, Klareskog L, van Vollenhoven RF. Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercept (Enbrel): results from the STURE registry at Karolinska University Hospital. Scand J Rheumatol 2005;34:353-8.

48) Valesini G, Montecucco C, Cutolo M. Recommendations for the use of biologic (TNF-alpha blocking) agents in the treatment of rheumatoid arthritis in Italy. Clin Exp Rheumatol 2006;24:413-23.

49) Furst DE, Wallis R, Broder M, Beenhouwer DO. Tumor necrosis factor antagonists: different kinetics and/or mechanisms of action may explain differences in the risk for developing granulomatous infection. Semin Arthritis Rheum 2006;36:159-67.

50) Desai SB, Furst DE. Problems encountered during anti-tumour necrosis factor therapy. Best Pract Res Clin Rheumatol 2006;20:757-90.

51) Geyer M, Muller-Landner U. “Rationale of using different biological therapies in rheumatoid arthritis”. Arthritis Res Ther 2010,12:214.

52) Bathon JM, Martin RW, Fleischmann RM et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000;343:1586-93.

53) Salvarani C, Olivieri I, Pipitone N et al. Recommendations of the Italian Society for Rheumatology for the use of biologic (TNF-α) agents in the treatment of psoriatic arthritis. Clin Exp Rheumatol 2006;24:70-78.

54) Salvarani C, Pipitone N, Marchesoni A et al. Recommendations for the use of biologic therapy in the treatment of psoriatic arthritis: update from the Italian Society for Rheumatology. Clin Exp Rheumatol 2011;29(Suppl. 66):S28-S41.

55) Gossec L, Smolen JS, Gaujoux-Viala C et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis 2012;71:4-12.

56) Mease PJ, Goffe BS, Metz J et al. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet 2000;356:385–90.

57) Mease PJ, Gladman DD, Ritchlin CT et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:3279–89.

58) Kavanaugh A, McInnes I, Mease P et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum 2009;60:976–86.

59) Ash Z, Gaujoux-Viala C, Gossec L et al. A systematic literature review of conventional and biologic drug therapies for the treatment of psoriatic arthritis: current evidence informing the EULAR recommendations for the management of Psoriatic Arthritis. Ann Rheum Dis 2012 Mar;71:319-26. 60) Soriano ER, Acosta-Felquer ML, Luong P, Caplan L. Pharmacologic treatment of psoriatic arthritis and axial spondyloarthritis with traditional biologic and non-biologic DMARDs. Best Pract Res Clin Rheumatol 2014;28:793-806 .

61) Soubrier AS, Bele-Philippe P, Cortet B et al. Treatment response, drug survival and safety of anti-tumour necrosis factor α therapy in 193 patients with psoriatic arthritis: A twelve-year “real life” experience. Joint Bone Spine 2015;82:31-7.

62) Di Minno MN, Peluso R, Iervolino S et al. Obesity and the prediction of minimal disease activity: a prospective study in psoriatic arthritis. Arthritis Care Res 2013;65:141–7.

63) Saad AA, Ashcroft DM, Watson KD et al. BSRBR. Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an observational study from the British Society for Rheumatology Biologics Register. Rheumatology 2010;49:697–705.

64) Kristensen LE, Gülfe A, Saxne T et al. Efficacy and tolerability of anti- tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish Arthritis Treatment Group register. Ann Rheum Dis 2008;67:364–9.

65) Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM et al. Adalimumab for the Treatment of Patients With Moderately to Severely Active Psoriatic

Arthritis Results of a Double-Blind, Randomized, Placebo-Controlled Trial. Arthritis Rheum 2005;52:3279–89.

66) Gladman D, Mease PJ, Ritchlin CT et al. Adalimumab for Long-Term Treatment of Psoriatic Arthritis Forty-Eight Week Data From the Adalimumab Effectiveness in Psoriatic Arthritis Trial. Arthritis Rheum 2007;56:476–88. 67) Mease PJ, Ory P, Sharp JT, Ritchlin CT et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis 2009;68:702–9.

68) Saad AA, Ashcroft DM, Watson KD et al. Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society for of Rheumatology Biologics Register. Arthritis Res Ther 2009;11:R52.

69) Tubach F, Salmon D, Ravaud P et al. Risk of tuberculosis is higher with antitumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective french research axed on tolerance of biotherapies registry. Arthritis Rheum 2009;60:1884-94.

70) Lim LL, Fraunfelder FW,Rosenbaum JT. Do tumor necrosis factor inhibitors cause uveitis? A registry-based study. Arthritis Rheum 2007;56:3248-52.

71) Bonafede M, Johnson BH, Fox KM,Watson C,Gandra SR. Treatment patterns with etanercept and adalimumab for psoriasi diseases in real-world setting. J Dermatolog Treat 2013; 24: 369-373

72) Chastek B, Fox KM, Watson C, Gandra SR. Etanercept and adalimumab treatment patterns in psoriatic arthritis patients enrolled in a commercial health plan. Adv Ther 2012;29:691-7.

73) Fabbroni M, Cantarini L, Caso F et al. Drug retention rate and treatment discontinuation among anti-TNFα agents in psoriasi arthritis and ankylosing spondylitis in clinical practice. Mediators Inflamm 2014;2014:862-969.

74) Jobanputra P, Maggs F,Deeming A et al. A randomised efficacy and discontinuation study of etanercept versus adalimumab (RED SEA) for

rheumatoid arthritis: a pragmatic, unblinded, non-inferiority study of first TNF