Advances in molecular immunology and rapid technical evolution during the past two decades have led to a new class of medicines called biologics. Recently, a large number of biologics, or biologic immunomodulators, directed towards an array of immune–mediated diseases, have entered the market. This has lead to a dramatic change in the immunotherapy of autoimmune diseases, as biologics present new potential to improve or substitute conventional immunosuppressive therapies. According to literature, biologics are used by only a small number of a health plan’s members, (approximately one per cent), but a single occurrence can be relatively expensive. Furthermore, there is an indication that the frequency of use and cost of biologics are on the rise, and as more biologics enter the market, health plans and employers face the challenge of controlling costs while ensuring that biologics are affordable. The general objective of this study was to determine the prevalence and cost of biologic immunomodulating medicine in the treatment of certain autoimmune diseases during the period 2005 to 2008 in a section of the private health care sector of South Africa, by employing a medicine claims database as a source to obtain necessary information. A quantitative, retrospective drug utilisation review (rDUR) was performed on computerised medication records (medicine claims data) for four consecutive years (i.e. 2005 to 2008) provided by a pharmacy benefit management company (PBM). The study population consisted of all patients on the database who received at least one medicine item with adalimumab, etanercept, infliximab, interferon beta–1a, interferon 1–b or rituximab as active ingredient and who were diagnosed with either rheumatoid arthritis (RA), multiple sclerosis (MS) or Crohn’s disease between 1 January 2005 and 31 December 2008. Between 2005 and 2008, an average of 1,305,201 patients appeared on the total database, and of these 0.055% (n = 713) received biologic immunomodulating medicine. More than two thirds of biological users were female and most patients who received these medicine items were between the ages of 39 and 64 years, followed by those patients aged between 25 and 39 years. Biologic immunomodulating medicine items (n = 11,914) and biologic prescriptions (n = 9,537) represented 0.016% of the total number of medicine items (N = 76,129,173) and 0.030% of the total number of prescriptions (N = 31,985,153). The percentage contribution of biologic immunomodulators to the total number of medicine items and prescriptions on the total database increased each year, and in four years’ time the percentage of all the medicine items on the total database that included biologic immunomodulators had tripled, from 0.009% to 0.023%. The total cost of biologic immunomodulating medicine accounted for 1.278% of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM between 2005 and 2008. The percentage contribution of biologic immunomodulators to the total medicine expenditure also increased from one year to another for the four–year study period. The average cost of a biologic immunomodulating medicine item increased with 71.10% from 2005 (R5602.71 ± 2166.61) to (R9586.25 ± 5956.56) in 2008. The CPI for biologic immunomodulators, (CPI = 60.00 for 2005; CPI = 74.62.17 for 2006; CPI = 85.26 for 2007; and CPI = 86.96 for 2008) indicated that biologic immunomodulating medicine items were relatively expensive and the d–value between the average cost per biologic immunomodulator and the average cost per non–biological medicine item (d–value = 2.54 in 2005, d–value = 3.32 in 2006, d–value = 2.23 in 2007 and d–value = 1.59 in 2008) furthermore indicated that the impact of biological therapies was large and practically significant. Rheumatoid arthritis patients represented 19.78% of the total number of patients (n = 713) who claimed the biologic immunomodulators during the four–year period, MS patients (n = 172) represented 24.12% and Crohn’s patients (n = 11) represented 1.5%. Biological drugs prescribed to RA patients represented 0.28% (n = R20, 708,818.82) of the total cost (N = R7, 483,759,176.23) of all medication claimed through the PBM during the four–year period, while those prescribed to MS patients represented 0.41% (R30, 922,520.07) and those prescribed to Crohn’s disease patients represented 0.015% (R1, 108,568.02). Although biologic immunomodulating medicine items used in the treatment of RA, MS and Crohn’s disease are relatively expensive, it seems that the number of other medication prescribed to patients with these diseases decreased after treatment with biologics, which may influence the medicine treatment cost of these patients. It can be concluded that even though biologic immunomodulators are used by only a very small percentage of the total patient population in a section of the private health care sector of South Africa, they are relatively expensive and have a considerable impact not only the medical aid scheme, but also on the patient. / Thesis (M.Pharm (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2011.

<p>Reumatoidni artritis (RA) je hronično inflamatorno oboljenje zglobova koji nastaje usled poremećaja u regulaciji imunskih mehanizama. TNF-alfa jedan je od ključnih medijatora inflamacije u RA, a koji preko složenih mehanizama podstiče aktivnost osteoklasta koji dovodi do poremećaja u procesu ko&scaron;tanog remodelovanja u pravcu povećane ko&scaron;tane resorpcije koji se klinički može pratiti određivanjem nivoa markera ko&scaron;tane resorpcije i ko&scaron;tanog formiranja u urinu i serumu. Primenom TNF inhibitora započeo je novi koncept lečenja RA. Cilj rada: Utvrditi razliku mineralne ko&scaron;tane gustine (BMDg/cm2) i vrednosti ko&scaron;tanih biohemijskih markera-prokolagen tip 1N-terminalni propeptid (P1NP) i beta-crosslapsa pre uvođenja terapije, i nakon godinu dana sprovedene terapije TNF inhibitorima. Metode: Studija je sprovedena u Specijalnoj bolnici za reumatske bolesti Novi Sad jednim delom kao retrospektivno, a drugim delom prospektivno istraživanje, koje je obuhvatilo 50 bolesnica sa dijagnozom reumatoidnog artritisa kod kojih je postojala indikacija za uvođenje lekova iz grupe TNF inhibitora. Da bi u&scaron;le u studiju bolesnice su morale da ispune određene uključne/isključne kriterijume koji su bili vezani za dužinu trajanja RA i menopauze, način lečenja RA, stepen o&scaron;tećenja zglobova i prisutnost drugih oboljenja sa reperkusijom na ko&scaron;tano tkivo. Pored reumatolo&scaron;kog i fizikalnog pregleda određivani su faktori rizika za osteoporozu i prelome. Na početku i na kraju godinu dana po uvođenju terapije TNF inhibitora rađena je osteodenzitometrija na aparatu tipa &bdquo;Lunar&ldquo; merena na lumbalnoj kičmi i kuku kao i određivanje biohemijskih markera u serumu prokolagen tip 1 N-terminalni propeptid (P1NP) i betacrosslapsa ECLIA metodom. Rezultati: Prosečna starost bolesnica bila je 51,5 godina koje su u 84%, bolovale od RA do 5 godina kod kojih je u najvećem procentu dužina trajanja menopauze bila do dve godine, a u svojoj terapiji pored metotreksata su imale uključen TNF inhibitor, Etanercept 34%, Adalimubam 46%, Golimubam 9% i 2% Infliksimab.Pre uvođenja biolo&scaron;ke terapije najveći broj bolesnica 80% imalo je osteopeniju, 14% normalan nalaz, dok je osteoporoza zabeležena kod 6% bolesnica. Na kraju jednogodi&scaron;nje primene TNF inhibitora 18% bolesnica je imalo normalan osteodenzitometrijski nalaz, 78 % osteopeniji, a 4% osteoporozu. Ova promena je statistički značajna ( p=0,000). Nakon jednogodi&scaron;nje primene TNF inhibitora nije do&scaron;lo do smanjenja vrednosti BMD (g/cm&sup2;) merenog na lumbalnom delu kičme i kuka. Beleži se statističko značajno povećanje vrednosti T- skora (SD) merenog na lumbalnom delu kičme i vratu butne kosti. Vrednost ko&scaron;tanih biohemijskih markera P1NP i beta crosslapsa značajno su povećani nakon jednogodi&scaron;nje primene TNF inhibitora, pri čemu se beleži veće povećanje biohemijskog markera ko&scaron;tane sinteze, P1NP. Zaključak: Savremeni pristup lečenja reumatoidnog artritisa podrazumeva primenu biolo&scaron;kih lekova kao &scaron;to su TNF inhibitori koji značajno suzbijaju inflamaciju i dovode do smanjenja odnosa RANKL/OPG sistema, čime se inhibira dejstvo osteoklasta i sprečava gubitak mineralne ko&scaron;tane gustine. Primena TNF inhibitora nakon godinu dana sprečila je pad vrednosti BMD (g/cm&sup2;), povećana je vrednost T- skora (SD) i vrednosti ko&scaron;tanih biohemijskih markera, posebno markera ko&scaron;tane sinteze. Uprkos velikom broju studija vezanih za dejstvo TNF inhibitora na kost, za sada nema dovoljan broj istraživanja o njegovom uticaju na sprečavanju osteoporoze i preloma kostiju i nivou vrednosti ko&scaron;tanih biohemijskih markera posebno u dužem periodu praćenja, &scaron;to će biti verovatno predmet daljih istraživanja.</p> / <p>Rheumatoid arthritis (RA) is a chronic inflammatory joint disease resulting from compromised regulation of immune mechanisms. TNF-alpha is one of the key inflammation mediators in RA that, through complex mechanisms stimulates osteoclast activity, thereby modifying the bone remodeling process in the direction of increased bone resorption that can be clinically monitored by determining the level of bone resorption and bone formation markers in urine and serum. Use of TNF has initiated a new concept in RA treatment. Aims: To determine the differences in bone mineral density (BMD, g/cm2) and values of biochemical markers in bone procollagentype 1 N-terminal propeptide(P1NP) and betacrosslaps before and after yearlong TNF inhibitor therapy. Methods: The study was conducted at the Special Hospital for Rheumatic Diseases Novi Sad partly as retrospective and partly as prospective research, which involved 50 female patients diagnosed with rheumatoid arthritis in whom introduction of medications from the TNF inhibitor group was indicated. To be included in the study, patients had to meet certain inclusion/exclusion criteria related to RA and menopause duration, RA treatment, degree of joint impairment, and presence of comorbidities with repercussions for bone tissues. In addition to rheumatological and physical examinations, risk factors for osteoporosis and fractures were determined. At the beginning and one year after commencing TNF inhibitor therapy, osteodensitometry was performed using &ldquo;Lunar&rdquo; apparatus, taking measurements on lumbar spine and hip, and serum levels of biochemical markers procollagentype 1 Nterminal propeptide(P1NP) and beta-crosslaps were determined via ECLIA method. Results: Mean patient age was 51.5 years, 84% of whom suffered from RA for up to 5 years, and in the greatest percentage experienced menopause for two years, receiving therapy that in addition to methotrexate included a TNF inhibitor, Etanercept 34%, Adalimumab 46%, Golimumab 9%, and 2% Infliximab. Prior to commencing biological therapy, majority of patients 80% suffered from osteopenia, 14% had normal findings, and osteoporosis was recorded in 6% of patients. At the end of yearlong TNF inhibitor therapy, 18% of patients had normal osteodensitometry findings, 78% had osteopenia and 4% osteoporosis. This change was statistically significant (p = 0.000). As a result of yearlong TNF inhibitor therapy no reduction occurred in BMD (g/cm&sup2;) values in lumbar spine and hip. Statistically significantly higher T scores (SD) pertaining to lumbar spine and femur were measured. Values of biochemical markers P1NP and beta-crosslaps significantly improved after yearlong TNF inhibitor therapy, whereby a greater increase was recorded in the biochemical bone synthesis marker, P1NP. Conclusion: Advanced rheumatoid arthritis treatment involves the use of biological compounds such as TNF inhibitors that significantly suppress inflammation and reduce the RANKL/OPG ratio, thereby inhibiting osteoclast activity and preventing bone mineral loss. TNF inhibitor therapy after one year prevented reduction in the BMD (g/cm&sup2;) levels, while increasing the T score (SD) and bone biochemical marker values, bone synthesis marker in particular. Despite a large number of studies related to the TNF inhibitor effect on bone, there is presently not enough research on its influence on osteoporosis and bone fracture prevention and bone biochemical marker levels, especially over longer periods, which will likely be the topic of further research.</p>