6, 21...,.,..,..,. - (RA) -,. (AS) (PsA). (Disease-modifying antirheumatic drugs, DMARDs). DMARDs 21. - RA, AS PsA. 21. RA, DMARDs. Leflunomide (Arava)., RA Methotrexate Leflunomid. DMARDs - 5 29. - RA AS. (NSAIDs DMARDs) AS. -,, 12. TNF-.42% RA.4% AS., DMARDs... 75%., DMARDs. -,,, -. -. :,,, R. Stoilov,. Ivanova, N. Stoilov and S. Marincheva. COST ANALYSIS OF THE TREATMENT OF RHEUMATOID ARTHRITIS, ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS WITH SYN- THETIC AND BIOLOGIC DISEASE MODIFYING ANTIRHEUMATIC DRUGS FOR 21 IN BULGARIA Summary. Early diagnosis and early aggressive treatment of rheumatoid arthritis (RA) are among the major factors for delaying the rate of bone-tendon destructions and, respectively, of invalidism. Such observations have also been reported in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Regarding this, great hopes are reposed in disease-modifying antirheumatic drugs (DMARDs) and, particularly, in biologic agents. The aim of this study was to determine and evaluate the utilization of synthetic and biologic DMARDs in the treatment of RA, AS and PsA for 21 in Bulgaria. For 21, an increase of the number of RA treatments with synthetic DMARDs was registered, predominantly attributed to treatments with leflunomide (Arava). This fact can be explained by the consensus achieved by the members of the Bulgarian Society for Rheumatology that a biologic agent is to be included in the treatment of RA, only after a lack of response to methotrexate and leflunomide. In 21, expenditures for biologic DMARDs were 5 times higher compared with these for the preceding 29. This increase was attributed mostly to RA and AS treatments. The lack of sufficiently effective synthetic medicinal products (NSAIDs and DMARDs) for the treatment of AS, has stimulated the use of biologic agents. Despite the increased utilization of biologic agents in the treatment of inflammatory joint diseases in Bulgaria, the proportion of their users is too small, compared with the average 12% in the other EU countries. In our country,.42% of the RA patients and.4% of the AS patients are on TNF- blockers. This indicates that the access to expensive and highly effective treatments with biologic DMARDs is very limited in Bulgaria. The reimbursement policy of the health insurance system is the key to improving the access to biologic agent treatment. The reimbursement of only 75% of the cost of this treatment is still far beyond patient affordability. The proportion of patients treated with synthetic DMARDs is still too low. Of course, reimbursement of synthetic DMARDs is of importance, but it has no such heaviness as this of biologic agents. Rheumatologist s opinion and patient's compliance are of greater importance. Key words: rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, treatment access
61... (RA) -.. -. - [5]. [1]. RA -.36 1% [7, 2]. - : -.85% [28],.8% [11]. RA -.31%,.46% [21, 29],.5 1% [25]. - RA.48% [15]. 28 19-6 158, - RA 29 711 [15]. - RA. 1998. 26-32. [17], 22. 1.6. (1.21. - 38. ) [7]., RA HAQ-DI Steinbrocker criteria 3718.3 22 946 V [14]. ACR 3 RA -, [3]. (NSAIDs),, - (Disease-modifying antirheumatic drugs, DMARDs). -. DMARDs - ( )., RA DMARDs,, DMARDs [16]. - 2 -, TNF-. - - - [8, 17, 27, 3], -. - DMARDs. -, : 1) - RA DAS28 5.1; 2) - - DMARDs, -,. TNF- - (AS) (PsA). AS HLA-B27.1-1.4% [19]. AS.8% [22],.55% [6],.13%.52% [12]., -.2.3% [15]. -,, AS - 15 4. PsA.5 1% [15]. - -,. - - DMARDs 21. - RA, AS PsA. : ISM Methotrexate, Leflunomide (Arava), Sulfasalazine (Salazopyrin), Penicillamine (Cuprenil), Hydroxychloroquine, Azathioprine (Imuran), Ciclosporin A, Cyclophosphamide, Adalimumab (Humira), Etanercept (Enbrel), Infliximab (Remicade), Rituximab (Mabthera) 21.;
62.,.,.. TNF- ; - RA, AS PsA., RA, - - [9]. - -, - [31]. DMARDs, -,. - - - RA., - RA,, -, RA. - TNF- Arava,. - - -, Methotrexate, Sulfasalazine DMARDs. DMARDs ( TNF- Adalimumab Etanercept). 1 -, 29 21. DMARDs,., 29-72 - RA..25% - (. 1). 1., DMARDs. 29 21. 1 1. 29 21 29 21 29 21 Adalimumab (Humira) 5 123 146% 14 872 14 824 743 6 1 823 317 Etanercept (Enbrel) 22 78 255% 13 648 12 66 36 856 983 273 Infliximab (Remicade) NA NA NA NA Rituximab (Mabthera) NA NA NA NA Methotrexate 3 276 1% 45 36 135 97 95 Leflunomide (Arava) 22 274 36% 963 933 194 526 25 5653 Sulfasalazine (Salazopyrin) 631 357 43% 177 161 24 72 6 615 Penicillamine (Cuprenil) 3 NA 262 NA 786 NA Hydroxychloroquine 4 1 75% 87 74 34 8 74 Azathioprine (Imuran) 25 1 6% 167 146 4175 146 Ciclosporin A NA NA NA NA Cyclophosphamide NA NA NA NA 21. TNF- (Adalimumab Etanercept) 21 (RA 125, AS 61, PsA 15). - 29., 72, 179%. 21 - - TNF- (Adalimumab Etanercept). 2 831 93-1 161 489 29., - 144% (. 1). - TNF- -
63... [16]. 21. - RA, TNF-. - Adalimumab (Humira) Etanercept (Enbrel).42% RA (29 711 ). - TNF RA -. 5 2% - TNF- [13]. - 3 28% [13]., 12% R TNF- [13]., -. (12 66-14 824 ) - (75%) -. +144% 2 831 93 2 5 2 1 5 +146% 1 161 489 1 +36% 5 347 621 471 859 27 28 29 21. 1. TNF-. 27-21. ( ) 21. 61,.4% - AS (15 4 ), Adalimumab Etanercept. TNF- AS NSAIDs, - DMARDs KS. - TNF- AS. PsA -, 15, -,.. 21. Adalimumab (Humira) Etanercept (Enbrel) -.. 1, - TNF- - - 347 621 27. 2 831 93 21., 27. - TNF-, 28. - 5%, 25%, 36%. 29 21. 75% TNF-,. 29 21. 146 144% (. 1,. 2).. 2, - DMARDs -. -. Enbrel 21. 12 66 1 - - 29. Humira 21. 14 824 29.
64.,.,.. 2. DMARDs 1 - [1].. Sulfasalazine (Salasopyrin) 1942 65 161 Aurothiomalic acid 1948 3-4 NA Hydroxychloroquine 1952 1-15 74 Penicillamine (Cuprenil) 1957 15-25 262 Auranofin 1982 44 NA Methotrexate 1 mg/. 1988 2-42 36 Azathioprine (Imuran) 1978 NA 146 Cyclosprorin A 1993 3-4 NA Leflunomide (Arava) 1998 144 933 Etanercept (Enbrel) 1998 9-15 1266 Infliximab (Remicade) 1998 1-18 NA Anakinra (Kinret) 21 1-12 NA Adalimumab (Humira) 23 1-15 14824 Rituximab (Mabthera) 26 7-1 NA Abatacept (Orencia) 26 15-19 NA - 21. Humira Enbrel. Infliximab (Remicade), -TNF-, [2]. 1, - Humira 61%, Enbrel 39%., 65% TNF- Humira 35% Enbrel (. 2). 3 273 183 246 817 2 193 754 216 514 18 586 153 637 123 944 13 18 125 393 119 668 13 376 1 7 857 28 272 71 226 93 682 35 648 68 234 4 96 65 269 14 826 112 585 112 68 85 349 21 829. 2. HUMIRA, ENBREL REMICADE. 21. ( )
65... DMARDs 21. 3447 RA DMARDs., 11.6% -., DMARDs,., RA. - -, -, - -. - -. (.. 2). Methotrexate ( ) 36 6 -., - - 9.1% RA. - 21. ( 1%), Arava. Leflunomide (Arava).9% RA (.. 1). 36% TNF- - Methotrexate Leflunomide. Sulfasalazine Hydroxychloroquine, 43% 75%. 21. 1.2% Sulfasalazine (Salasopyrin).3% Hydroxychloroquine. Penicillamine (Cuprenil) Imuran, Cyclosprorin A Cyclophosphamide RA (.. 1)., -. - -, -, TNF [13].. 2, - DMARDs,, -. Methotrexate 1 mg/ 36, 2-42. (Sulfasalazine, Hydroxychloroquine, Leflunomide), Arava - 933 144. Arava 21. 255 653, 31%. DMARDs 21. 3 229 624. 283193 TNF-, 87.7 %. DMARDs - 398 531, 12.3% DMARDs (. 3). 29. DMARDs 1 154 399, 537 315, 617 84, 47%, 53% -. 29. 21. : 1) - 2) DMARDs. 29. DMARDs 47 53%, 21. 87.7 12.3% (.. 3)., - -,, -. -, - - DMARDs,. - - /,., /. TNF - Etanercep Adalimumab (12 66-14 824 ) - DMARDs. TNF - RA - Methotrexate., - TNF- - - - [18].
66.,.,.. - TNF RA [23]. (, ) DMARDs RA 1998-21., - - 216, Leflunomide 21, Azathio- prine 1878, Sulfasalazine 119, Methotrexate 78, Hydroxychloroquine 684 [24]., - DMARDs a a. -, 28 29. 6.3% - TNF-. 1 9 1 9 3 229 624 2 831 93 8 8 7 7 6 5 1 % 617 84 537 315 6 5 1 % 87.7 4 4 3 2 1 53 % 47 % 3 2 398 531 1 12.3 29 21. 3... - 29 21.. 4., 879 997 471 29. 11% 959 463 873., DMARDs 18%.13% 29..34% 21. -. DMARDs.,. 9% -, 9%. -,,., - -, -. - -,,. - - -,, -., TNF - -, -, -, - - - [4].
67... 3 5 + 18% 3 229 624 98 96 959 463 873 94 92 1 75 1 154 399 9 88 879 997 471.34% 291 212 86 84.13% 29 21 1. 2.. 4. ( ) 29 21.. ( ) TNF - RA, AS PsA [26].,.. -, -. -., [13].., - -,,, TNF,.,, - ( ), -, - [13]. - - DMARDs ( -, )., TNF., -. 21. RA, DMARDs. Leflunomide (Arava) Methotrexate., RA Methotrexate Leflunomid. DMARDs -. RA AS. (NSAIDs DMARDs) - AS -. - -, -., - DMARDs. - -. 25, 5, 15, 2. 6 18-. -. - (,, ), [1]. DMARDs. 12 66 14 824, 1 mg/. 36. - -
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