Time course of changes in lipid profile measures in patients with early psoriatic arthritis during adalimumab therapy

Patients with psoriatic arthritis (PsA) have a higher risk of cardiovascular disease (CVD) compared with the general population. Inflammation and traditional CVD risk factors (RFs), including dyslipidemia, make a significant contribution to the development of CVD and their complications in patients with PsA.

Objective: to assess the time course of changes in lipid profile measures in patients with early PsA (ePsA) during adalimumab (ADA) treatment for 3-months.

Subjects and methods. The investigation enrolled 16 patients (11 women, 5 men; median (Me) age, 45.5 years) with early PsA (ePsA) (disease duration, 7.7 months). ADA was administered subcutaneously at doses of 40 mg once every 2 weeks for 3 months. Before and 3 months after the start of ADA therapy, DAS, C-reactive protein levels, and traditional CVD RFs, including lipid profile measures (total cholesterol, TC, low-density lipoprotein cholesterol, LDL-C, triglycerides, TG, high-density lipoprotein cholesterol, HDL-C, and atherogenic coefficient, AC) were estimated. Ten-year risk for fatal CVD was assessed using the SCORE scale.

Results and discussion. Lipid profile disorders mainly associated with elevated LDL-C levels were revealed in 11 (69%) patients; according to the SCORE scale, the total 10-year risk for fatal CVD was low and moderate in 10 (62.5%) and 6 (37.5%) patients, respectively. A correlation was found between the baseline DAS and TG (r=0.53; p<0.05) and AC (r=0.57; p<0.05); between HDL levels and DAS (r=-0.68; p<0.05), and between the number of tender (r=-0.63; p<0.05) and swollen joints (r=-0.65; p<0.05).

Three months after starting ADA Median level of TC increased from 4.9 [4.5; 5.9] to 5.5 [4.9; 6.3] mmol/L (p=therapy, 15 (94%) patients achieved remission of ePSA; one (6%) patient showed a low disease activity. 0.01) and TG — from 0.8 [0.7; 1.4] to 1.1 [0.9; 1.4] mmol/L (p=0.03). There were no significant changes in the level of LDL-C and HDL-C, and CA, their medians at the beginning and end of therapy were 3.3 [2.8; 4.1] and 3.6 [3.3; 4.1]; 3.0 [1.2; 1.  5] and 1.3 [1.2; 1.6]; 2.6 [2.3; 3.6] and 3.2 [2.4; 3.6] mmol/L, respectively. There was a tendency to increase the frequency of non-target TC values from 44 to 75%, LDL-C from 69 to 81%, TG from 12.5 to 19%, and AC from 37.5 to 62.5% (p>0.05).

Conclusion. Lipid profile changes were found in 69% of patients with ePSA and correlated with disease activity. The lower inflammatory activity during ADA therapy was accompanied by elevated TC and TG levels.

1. Yim KM, Armstrong AW. Updates on cardiovascular comorbidities associated with psoriatic diseases: epidemiology and mechanisms. Rheumatol Int. 2017;37(1):97-105. doi: 10.1007/s00296-016-3487-2

2. Eder L, Wu Y, Chandran V, et al. Incidence and predictors for cardiovascular events in patients with psoriatic arthritis. Ann Rheum Dis. 2016;75(9):1680-6. doi: 10.1136/annrheumdis-2015-207980

3. Favarato MH, Mease P, Goncalves CR, et al. Hypertension and diabetes significantly enhance the risk of cardiovascular disease in patients with psoriatic arthritis. Clin Exp Rheumatol. 2014;32(2):182-7. PMID: 24480317

4. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016;252:207-74. doi: 10.1714/2729.27821

5. Colantonio LD, Bittner V, Reynolds K, et al. Association of serum lipids and coronary heart disease in contemporary observational studies. Circulation. 2016;133:256-64. doi: 10.1161/CIRCULA-TIONAHA.115.011646

6. Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 2007;370:1829-39. doi: 10.1016/S0140-6736(07)61778-4

7. Tekin NS, Tekin IO, Barut F, Sipahi EY. Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of plasma lipid levels in psoriatic patients. Mediators Inflamm. 2007;2007:78454. doi: 10.1155/2007/78454

8. Azfar RS, Gelfand JM. Psoriasis and metabolic disease: epidemiology and pathophysiology. Curr Opin Rheumatol. 2008;20:416-22. doi: 10.1097/BOR.0b013e3283031c99

9. Jones SM, Harris CP, Lloyd J, et al. Lipoproteins and their sub¬fractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease. Ann Rheum Dis. 2000;59:904-9. doi: 10.1136/ard.59.11.904

10. Pietrzak A, Chabros P, Grywalska E, et al. Serum lipid metabolism in psoriasis and psoriatic arthritis — an update. Arch Med Sci. 2019;15(2):369-75. doi: 10.5114/aoms.2018.74021

11. Mehta NN, Li R, Krishnamoorthy P, et al. Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis. Atherosclerosis. 2012;224(1):218-21. doi: 10.1016/j.atherosclerosis.2012.06.068

12. Holzer M, Wolf P, Inzinger M, et al. Anti-psoriatic therapy recovers high-density lipoprotein composition and function. J Invest Dermatol. 2014;134(3):635-42. doi: 10.1038/jid.2013.359

13. 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(1):4-12. doi: 10.1136/annrheumdis-2011-200350

14. Kohm M, Burkhardt H, Behrens F. Anti-TNFа-therapy as an evidence-based treatment option for different clinical manifestations of psoriatic arthritis. Clin Exp Rheumatol. 2015;33(5 Suppl 93):S109-14. PMID: 26472504

15. Van Sijl AM, Peters MJ, Knol DL, et al. The effect of TNF-alpha blocking therapy on lipid levels in rheumatoid arthritis: a meta-analysis. Semin Arthritis Rheum. 2011;41(3):393-400. doi: 10.1016/j.semarthrit.2011.04.003

16. Daien CI, Duny Y, Barnetche T, et al. Effect of TNF inhibitors on lipid profile in rheumatoid arthritis: a systematic review with metaanalysis. Ann Rheum Dis. 2012;71(6):862-8. doi: 10.1016/j.semarthrit.2011.04.003

17. Myasoedova E, Crowson CS, Kremers HM, et al. Lipid para-dox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann Rheum Dis. 2011;70(3):482-7. doi: 10.1136/ard.2010.135871

18. Chandran V, Schentag CT, Gladman DD. Sensitivity and specificity of the CASPAR criteria for psoriatic arthritis in a family medicine clinic setting. J Rheumatol. 2008;35(10):2069-70. PMID: 18843760

19. Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: aproposed objecti vetarget for treatment. Ann Rheum Dis. 2010;69(1):48-53. doi: 10.1136/ard.2008.102053

20. Klimov AN. Prichiny i usloviya razvitiya ateroskleroza. Preventivnaya kardiologiya [The reasons and conditions of development atherosclerosis. Preventive cardiology]. Moscow: Medicine; 1977 (In Russ.).

21. Ma C, Harskamp CT, Armstrong EJ, Armstrong AW. The associa¬tion between psoriasis and dyslipidaemia: a systematic review. Br J Dermatol. 2013;168(3):486-95. doi: 10.1111/bjd.12101

22. Ramonda R, Lo Nigro A, Modesti V, et al. Atherosclerosis in pso¬riatic arthritis. Autoimmun Rev. 2011;10(12):773-8. doi: 10.1016/j.autrev.2011.05.022

23. Otocka-Kmiecik A, Mikhailidis DP, Nicholls SJ, et al. Dysfunctional HDL: a novel important diagnostic and therapeutic target in cardiovascular disease? Prog Lipid Res. 2012;51:314-24. doi: 10.1016/j.plipres.2012.03.003

24. Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993-2000. doi: 10.1001/jama.2009.1619

25. Catapano AL, Graham I, de Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(39):2999-3058. doi: 10.1093/eurheartj/ehw272

26. Banach M, Serban C, Aronow WS, et al. Lipid, blood pressure and kidney update 2013. Int Urol Nephrol. 2014;46:947-61. doi: 10.1007/s11255-014-0657-6 

27. Nikolic D, Castellino G, Banach M, et al. PPAR agonists, atherogenic dyslipidemia and cardiovascular risk. Curr Pharm Des. 2017;23(6):894-902. doi: 10.2174/1381612822666161006151134

28. Oliviero F, Sfriso P, Baldo G, et al. Apolipoprotein A-I and cholesterol in synovial fluid of patients with rheumatoid arthritis. Clin Exp Rheumatol. 2009;27:79-83. PMID: 19327233

29. Batuca J, Lamy M, Neves M, et al. Anti-apolipoprotein A-I (ApoA-I) antibodies have different target epitopes in different clinical conditions. Atherosclerosis. 2017;263:216-7. doi: 10.1016/j.atherosclerosis.2017.06.705

30. Ernste FC, Sanchez-Menendez M, Wilton KM, et al. Cardiovascular risk profile at the onset of psoriatic arthritis: a population-based cohort study. Arthritis Care Res (Hoboken). 2015;67(7):1015-21. doi: 10.1002/acr.22536

31. Navarini L, Margiotta DPE, Costa L, et al. Performance and calibration of the algorithm ASSIGN in predicting cardiovascular disease in Italian patients with psoriatic arthritis. Clin Rheumatol. 2019;38(4):971-6. doi: 10.1007/s10067-019-04442-3

32. Gonzalez-Juanatey C, Miranda-Filloy JA, Amigo-Diaz E, et al. Endothelial dysfunction in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum. 2007;57(2):287-93. doi: 10.1002/art.22530

33. Sattar N, McCarey DW, Capell H, McInnes IB. Explaining how «high-grade» systemic inflammation accelerates vascular risk in rheumatoid arthritis [review]. Circulation. 2003;108:2957-63. doi: 10.1161/01.CIR.0000099844.31524.05

34. Peters MJ, van Sijl AM, Voskuyl AE, et al. The effects of tumor necrosis factor inhibitors on cardiovascular risk in rheumatoid arthritis. CurrPharm Des. 2012;18:1502-11. PMID: 22364134

35. Chighizola C, Schioppo T, Ingegnoli F, et al. Potential effect of anti-inflammatory treatment on reducing the cardiovascular risk in rheumatoid arthritis. Curr Vasc Pharmacol. 2012;10:639-46. PMID: 22272912

36. Toms T, Symmons D, Kitas G. Dyslipidaemia in rheumatoid arthritis: the role of inflammation, drugs, lifestyle and genetic factors. Curr Vasc Pharmacol. 2010;8(3):301-26. PMID: 19758115

37. Ronda N, Greco D, Adorni MP, et al. Newly identified antiatherosclerotic activity of methotrexate and adalimumab: complementary effects on lipoprotein function and macrophage cholesterol metabolism. Arthritis Rheum. 2015;67(5):1155-64. doi: 10.1002/art.39039

38. Wu JJ, Poon KY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244-50. doi: 10.1001/archdermatol.2012.2502

39. Wu JJ, Guerin A, Sundaram M, et al. Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-а inhibitors versus methotrexate. J Am Acad Dermatol. 2017;76(1):81-90. doi: 10.1016/j.jaad.2016.07.042

40. Hoffmann JH, Knoop C, Enk AH, Hadaschik EN. Routine labo¬ratory parameter dynamics and laboratory adverse events in psoria¬sis patients on long-term treatment with Adalimumab, Etanercept, and Ustekinumab. Acta Derm Venereol. 2017;97(6):705-10. doi: 10.2340/00015555-2644

41. Hjuler KF, Bottcher M, Vestergaard C, et al. Association between changes in coronary artery disease progression and treatment with biologic agents for severe psoriasis. JAMA Dermatol. 2016;152(10):1114-21. doi: 10.1001/jamadermatol.2016.1984

42. Bissonnette R, Tardif JC, Harel F, et al. Effects of the tumor necrosis factor-а antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis: results of a randomized controlled trial. Circ Cardiovasc Imaging. 2013;6(1):83-90. doi: 10.1161/CIRCIMAGING.112.975730

43. Jokai H, Szakonyi J, Kontar O, et al. Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intima-media thickness in psoriasis: results of a pilot study. J Am Acad Dermatol. 2013;69(4):523-9. doi: 10.1016/j.jaad.2013.06.019

44. Tam LS, Kitas GD, Gonzalez-Gay MA. Can suppression of inflammation by anti-TNF prevent progression of subclinical atherosclerosis in inflammatory arthritis? Rheumatology (Oxford). 2014;53:1108-19. doi: 10.1093/rheumatology/ket454

45. Markelova EI, Novikova DS, Korotaeva TV, Loginova EYu. Dynamics of indicators of the thickness of the intima-media complex, stiffness of the vascular wall, daily monitoring of blood pressure in patients with early psoriatic arthritis as a result of therapy with an inhibitor of tumor necrosis factor-alpha. Ratsional'naya Farmakoterapiya v Kardiologii = Rational Pharmacotherapy in Cardiology. 2018;14(5):711-5 (In Russ.). doi: 10.20996/1819-6446-2018-14-5-711-715

46. Udachkina EV, Novikova DS, Popkova TV, et al. Time course of changes in blood lipid parameters in patients with early rheumatoid arthritis during treat-to-target antirheumatic therapy: According to 18-month follow-up findings. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(2):164-70 (In Russ.). doi: 10.14412/1995-4484-2016-164-170