Prescribing patterns of biologic immunomodulating medicine in the South African private health care sector

(1)

P rescribin g pattern s of biologic im m u n om odu latin g m edicin e in

P rescribin g pattern s of biologic im m u n om odu latin g m edicin e in th e

th e

S ou th A

S ou th A frican

frican

frican private

private

private health care sector

private

health care sector

Ilanca R oux

B .P harm

D issertation su bm itted in p artial fulfilm ent of the requ irem en ts for th e d egree M agister P h arm aciae in P harm acy P ractice at the P o tchefstroom cam pus of the N orth -W est U niversity.

S uperv isor: P rofessor M .S . L u bbe

C o-su pervisors: M rs. J.R . B urger

D r. J.C . L am prech t

P otchefstroom

(2)

_ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _

• I th an k m y L ord an d h eaven ly F a th er: T h an k you first of all for th e g ifts Y ou bestow ed on m e

th at en abled m e to do th is. T h an k yo u for giv in g m e stren gth an d p eace w h en I felt

d iscou raged and con fu sed, an d for giv in g m e th e w ord s to w rite w h en m in e seem ed to be

in ad equ ate. T h an k y ou for all of Y our b lessings, g ra ce an d lov in g-k in d n ess, b u t m ost of all,

th a nk yo u for surrou nd in g m e w ith am a z ing p eop le an d m ak ing th em p art of m y jo u rn ey and

p art o f m y life. A ll of th e g lory co m es to Y ou an d I p ray th at Y ou are th orou gh ly p leased .

I w ish to express m y sin cere gratitud e to th e m a ny peo p le w ho h elp ed an d su pp orted m e to realise

th is d issertatio n . T h e follow in g p eo p le d eserv e sp ecial ack n o w led gem en t:

• M y su p erv isor, P ro fesso r M .S . L u bbe: “T h a n k you ” d o es n ot begin to exp lain h o w m u ch all th e

h ard w ork , tim e an d effo rt yo u p ut in to th is stu dy are ap precia ted . T h an k you for go ing the

extra m ile an d ensu rin g tha t ev eryth in g w as alw ays accurate and u p to sta nd ard . T h an k you

for sh arin g you r w isdom an d ex p erien ce w ith m e. T o m e it w as a v ery reassu rin g exp erience to

b e ab le to rely on you r expert assistan ce thro ugho u t.

• M y co-su p erv iso r, D r. J.C . L am p rech t: T h a nk you fo r prov id in g th e m u ch n eed ed in sig ht in to

th e clin ical asp ects of th is stu d y an d for p rov id ing a fresh p ersp ectiv e w h en it w as n ecessary.

T h a n k you for you r con stru ctiv e con tribu tio n s a nd a dv ice an d fo r b eing so con sid erate w ith

regard to m y oth er o bligation s d u rin g th is p eriod .

• M rs. J.R . B u rger in yo u r capa city a s co-sup erv isor: T h an k you for ag reein g to get in volv ed in

th is stu dy a n d for alw ays being w illin g to h elp . Y our attention to d etail as w ell as yo ur

v alua ble adv ice and suggestio n s h av e b een greatly a p preciated a ll a long . Y ou r inp u t m ea n t

m u ch to m e an d I a m sin cerely gratefu l.

• M y fellow stu d ents: T h an k you so m u ch for m a k ing th is a m em orable exp erien ce an d for th e

o cca sion s th at w e co u ld lau gh togeth er w h en tim es w ere good an d co m p la in togeth er w h en th ey

w ere less good . B u t, th at’s research!

(3)

• T o S u n è a nd T iaan , th an k y ou fo r m a k ing th is fu n! T h an k yo u for alw ays being th ere, for yo ur

en couragem ent an d h elp , an d for being th e reason I w en t to th e office every d ay . T h is w ou ld

n o t h av e b een su ch a great exp erien ce if it h ad n ot b een for th e tw o of y ou .

• M y p aren ts, F ra n n ie a nd L in d a: I w an t to th an k you first of all for giv in g m e th e opp ortu n ity

to do th is. T h an k you for you r sup po rt an d m otiv atio n and for alw ays believ ing in m e. T h a n k

y ou for alw ay s en courag ing m e to do g rea t th in gs a n d for being at m y sid e throu g h every effort.

I d ed icate th is d issertatio n to yo u both , because w ithou t you it w o u ld not hav e been po ssible. I

lov e yo u .

• M y broth ers, R u an an d Jean d rè: I k n ow that yo u th in k it strang e th at an yon e w ou ld

w illin gly stu dy for long er th an w h at is ex p ected , b ut you n ev er sh o w ed a ny disco nten t that I

ch ose to d o th is and I am th a n kfu l. T h an k you for su p p orting m e an d m a k ing m e laugh

w h en ev er I to ok th in gs too seriou sly.

• W ayn e, you are m y rock . Y ou en cou raged a n d sup p ort ed m e ev ery step o f th e w ay , an d I

certain ly n eed ed th at. T h a n k you for all o f you r h elp ! T ha n k you for prov id in g a sho u lder for

m e to cry on w h en I felt discourag ed an d for being m y biggest fan w h en I su cceed ed . Y ou k ept

m e san e an d m otiva ted th rough out th is en tire pro cess, an d I am eterna lly gratefu l to yo u . I

lov e yo u .

• D r. S . E llis for yo ur exp ertise on th e sta tistical a n alysis.

• T o th e d ep artm en t of P h arm acy P ractice for fin a n cia l a n d tech n ical su p p ort.

• T o th e P h arm acy B en efit M an ag em ent co m p any for m ak ing th e d atabase availa ble.

• T o M s. M . T erblan ch e for ed iting th e lan gu age th is dissertatio n .

• T o M s. H . H offm a n an d M rs. A .M .E . P retorius for ed itin g th e b ibliograp h y.

(4)

_ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _

Title: Prescribing patterns of biologic immunomodulating medicine in the South African

private health care sector.

Keywords: biologics, biologic immunomodulating medicine, biological medicine,

autoimmune diseases, rheumatoid arthritis, multiple sclerosis, Crohn’s disease, pharmacoeconomics, drug utilisation review.

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

(5)

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.

(6)

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ ___ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ __ _ _ _ _ _ _ _ _ _ _ ___ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ __ _ _ _ _ _ _ _ _ _ _ ___ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ __ _ _ _ _ _ _ _ _ _ _ __

_ _

Titel: Voorskryfpatrone van biologiese immunomodulerende medisyne in die

Suid-Afrikaanse privaat gesondheidsorgsektor.

Sleutelwoorde: biologiese produkte, biologiese immunomodulerende medisyne, biologiese

medisyne, outo-immuun siektes, rumatoïde artritis, veelvuldige sklerose, Crohn se siekte, farmako-ekonomie, medisyneverbruiksevaluering.

Vooruitgang in molekulêre immunologie en _ŉ vinnige tegnologiese ontwikkeling gedurende die afgelope twee dekades het _ŉ nuwe groep geneesmiddels, bekend as biologiese

produkte, opgelewer. _ŉ Groot aantal biologiese produkte, of biologiese

immunomoduleerders, wat gemik is op _ŉ verskeidenheid van immuunbemiddelde

siektetoestande het onlangs die medisynemark bereik. Dit het aanleiding gegee tot _ŉ ingrypende verandering in immunoterapie van outo-immuun siektes, aangesien biologiese produkte nuwe potensiaal bied om konvensionele immuun-onderdrukkende terapieë te verbeter of te vervang. Volgens die literatuur word biologiese produkte gebruik deur slegs _ŉ klein gedeelte van ‘n mediese fonds se lede (ongeveer een persent), maar ‘n enkele voorval kan relatief duur wees. Boonop is daar _ŉ aanduiding dat die frekwensie van gebruik, sowel as die koste van biologiese produkte, besig is om te styg en soos wat nuwe biologiese produkte die mark bereik, word mediese fondse en werkgewers gekonfronteer met die uitdaging om die koste van hierdie produkte te beheer terwyl hulle moet verseker dat dit bekostigbaar is.

Die algemene doel van hierdie studie was om die voorkoms en koste van biologiese immunomodulerende medisyne in die behandeling van sekere outo-immuun siektes in ‘n gedeelte van die privaat gesondheidsorgsektor van Suid-Afrika te bepaal vir die periode 2005 tot 2008 deur gebruik te maak van _ŉ medisyne-eis databasis as _ŉ bron om die nodige inligting te bekom.

Die navorsingsmetode wat gebruik is in hierdie studie was ‘n kwantitatiewe, retrospektiewe medisyneverbruiksevaluering. Data was verkry vanaf gerekenariseerde medisyne rekords (medisyne-eis data) vir vier opeenvolgende jare (2005 tot 2008) wat beskikbaar gestel was deur ‘n apteek voordelebestuursmaatskappy. Die studie populasie het bestaan uit al die pasiënte op die databasis wat ten minste een medisyne item ontvang het wat adalimumab, etanercept, infliximab, interferon beta-1a, interferon 1-b of rituximab as aktiewe bestanddeel gehad het en wat gediagnoseer is met rumatoïde artritis (RA), veelvuldige sklerose (VS) of Crohn se siekte tussen 1 Januarie 2005 en 31 Desember 2008.

(7)

Tussen 2005 en 2008 het daar _ŉ gemiddeld van 1,305,201 pasiënte op die totale databasis verskyn, waarvan 0.055% (n = 713) biologiese immunomodulerende medisyne ontvang het. Meer as twee derdes van die pasiënte wat biologiese produkte gebruik het was vroulik en meeste van die pasiënte was tussen die ouderdomme van 39 en 64 jaar, gevolg deur pasiënte tussen die ouderdomme van 25 en 39 jaar. Biologiese immunomodulerende medisyne items (n = 11,914) en biologiese voorskrifte (n = 9,537) het 0.016% van die totale aantal medisyne items (N = 76,129,173) en 0.030% van die totale aantal voorskrifte (N = 31,985,153) verteenwoordig. Die persentasie van die totale aantal medisyne items en voorskrifte op die totale databasis wat deur biologiese immunomodulerende medisyne verteenwoordig is, het elke jaar verhoog. In vier jaar se tyd het die persentasie van al die medisyne items op die totale databasis, wat verteenwoordig is deur biologiese immunomoduleerders, verdriedubbel vanaf 0.009% tot 0.023%.

Die totale koste van biologiese immunomodulerende medisyne was verantwoordelik vir 1.278% van die totale koste (N = R7, 483,759,176.23) van al die medikasie wat geëis is deur die apteek voordelebestuursmaatskappy tussen 2005 en 2008. Die persentasie bydrae van biologiese immunomoduleerders tot die totale medisyne uitgawes het ook verhoog van een jaar na die volgende gedurende die vier-jaar periode. Die gemiddelde koste van ‘n biologiese immunomodulerende medisyne item het met 71.10% verhoog vanaf (R5602.71 ± 2166.61) in 2005 na (R9586.25 ± 5956.56) in 2008. Die koste-voorkoms indeks (“CPI”: Cost-prevalence index) vir biologiese immunomoduleerders, (CPI = 60.00 vir 2005; CPI = 74.62.17 vir 2006; CPI = 85.26 vir 2007; en CPI = 86.96 vir 2008) het aangetoon dat biologiese immunomodulerende medisyne items relatief duur was. Die d-waarde tussen die gemiddelde koste per biologiese immunomoduleerder en die gemiddelde koste per nie-biologiese medisyne item (d-waarde = 2.54 in 2005, d- waarde = 3.32 in 2006, d- waarde = 2.23 in 2007 en d- waarde = 1.59 in 2008) het boonop aangetoon dat die impak van biologiese terapieë groot en prakties betekenisvol was.

Pasiënte met RA het 19.78% van die totale aantal pasiënte (n = 713) verteenwoordig wat biologiese immunomoduleerders geëis het gedurende die vier-jaar periode. Pasiënte met VS (n = 172) het 24.12% verteenwoordig en pasiënte met Crohn se siekte (n = 11) het 1.5% verteenwoordig. Biologiese medisyne wat voorgeskryf is vir pasiënte met RA het 0.28% (n = R20, 708,818.82) van die totale koste (N = R7, 483,759,176.23) van alle medikasie wat deur die apteek voordelebestuursmaatskappy geëis is tussen 2005 en 2008 verteenwoordig. Biologiese medisyne wat voorgeskryf is vir pasiënte met VS het 0.41% (R30, 922,520.07) verteenwoordig en die wat voorgeskryf is vir pasiënte met Crohn se siekte het 0.015% (R1, 108,568.02) verteenwoordig.

(8)

Alhoewel die biologiese immunomodulerende medisyne wat gebruik word in die behandeling van RA, VS en Crohn se siekte relatief duur is, blyk dit of die aantal ander medisyne items wat voorgeskryf word vir pasiënte met hierdie siektetoestande afneem nadat hulle met biologiese produkte behandel is. Die medisyne behandelingskoste van hierdie pasiënte mag hierdeur beïnvloed word.

Die gevolgtrekking kan gemaak word dat, alhoewel biologiese immunomoduleerders deur slegs _ŉ klein gedeelte van die totale pasiënt populasie in _ŉ gedeelte van die privaat gesondheidsorg sektor van Suid-Afrika gebruik word, is hierdie middels relatief duur en het hulle _ŉ aansienlike uitwerking op beide mediese fondse en pasiënte as betalers.

(9)

_ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ ___ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ __ __ _ _ _ _ _ _ _ _ _ _ __ _ _ __ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ __ _ _ _

L IS T O F T A B L E S … … … ...

x ii

L IS T O F F I G U R E S … … ...… … … ...

xv ii

L IS T O F A B B R E V IA T I O N S … ...… … … ...… … … ..

x xi

L IS T O F S Y N O N IM S … … … ...… … … … ...

xxv

C ha pter 1

C ha pter 1: In trodu ction

1 .1

B ack gro u n d an d m o tivation for th e stu d y… … … …

…

… … … ...

… … ...

..

....

..

1 1 .2

1 .2

R esearch objectiv es… … … …

R esearch objectiv es… … … .

… .

… .… ...

… .

… ...

..

...

5 1 .2 .1

G en eral research objectiv e… … … .

6 1 .2 .2

S p ecific research objectiv es… … … …

6 1 .2 .2 .1

P h ase 1 : L iteratu re rev iew … … … ...

6 1 .2 .2 .2

P h ase 2 : E m p irica l in v estig atio n… … … ...

7 1 .3

1 .3

R esearch m eth ods… … … …

…

… … …

… …

… … …

… …

…

7 1 .3 .1

L iterature p h ase… … … ..

8 1 .3 .2

E m p irical p hase… … … ...… … … ....

8 1 .3 .2 .1

D ata sou rce a n d stu dy p opu latio n… … … .

8 1 .3 .2 .2

R esearch d esign … … … ...… … … .

9

(10)

T able of con tents

_ __ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _

1 .3 .2 .4

D ata analysis… … … ... ..

9 1 .3 .2 .5

R eliab ility and v alid ity of d ata… … … ..… … … ..

9 1 .3 .2 .6

E th ical consid eration s… … … ....

9 1 .4

1 .4

D iv isio n o f ch ap ters

D iv isio n o f ch ap ters … … … .

D iv isio n o f ch ap ters

… … … .

… … … ...

… … … .

..

1 0

1 .5

C h ap ter su m m ary

C h ap ter su m m ary … … … .

C h ap ter su m m ary

… … … .

… … … ...

1 0

C h ap te

C h ap terrrr 2

2

2 2 :

:

: A n O v erv iew of th e Im m u n e system a n d B iologic Im m u n om od u latin g M ed icin e

2222

I n trod u ctio n

I n trod u ctio n … … … …

… … … …

… … … .

… … … …

… .

1 1

2 .1

T h e im m u n e system

T h e im m u n e system … … … ....

… … … ....

… … … ...

… … … ....

....

1 1

2 .2

N o rm al im m u n e resp onses

N o rm al im m u n e resp onses… … … ...

… … … ...

....

1 3

2 .2 .1

T h e in n ate im m u n e response… … … .. ...

1 5

2 .2 .2

T h e a d aptiv e im m u n e resp on se… … … ...

1 9

2 .2 .2 .1

T h e ro le of B cells in im m u n e d efen ces… … … ...

2 3

2 .2 .2 .2

T h e ro le of T cells in im m u n e d efen ces… … … ...

2 4

2 .2 .3

A n tibod ies… … … …

2 6

2 .2 .3 .1

D efin itio n… … … .

2 6

2 .2 .3 .2

A n tibody stru ctu re… … … .

2 7

2 .2 .3 .3

G en eral fu n ction s of an tibod ies… … … ...

2 8

2 .2 .3 .4

A n tibody cla sses… … … ... ..

2 8

(11)

T able of con tents

_ __ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _

2 .2 .4 .1

O v erv iew … … … ...

2 9

2 .2 .4 .2

C ategories of cytok in es… … … ..

2 9

2 .3

A b n orm al im m u n e respon ses

A b n orm al im m u n e respon ses … … … .

… … … .

… … … ...

… … … .

3 2

2 .3 .1

H yp ersen sitiv ity… … … ...

3 2

2 .3 .2

Im m u n od eficien cy … … … ...

3 2

2 .3 .3

A u to im m u n ity… … … ..

3 2

2 .3 .3 .1

D efin ition… … … ....

3 2

2 .3 .3 .2

G en eral classifica tion… … … ....

3 3

2 .3 .3 .3

E tiology o f a u to im m u n e d iseases… … … ...

3 3

2 .4

B iolog

B iolog ics: A n O v erv iew

ics: A n O v erv iew

ics: A n O v erv iew … … … ...

… … … ...

3 5

2 .4 .1

In trod u ction… … … ....

3 5

2 .4 .2

A brief h isto ry of bio logics… … … .

3 5

2 .4 .3

C om p osition an d d ev elop m en t… … … ...

3 7

2 .4 .4

B iolog ics v ersus trad ition al sm all m o lecu le d ru gs… … … ..

3 8

2 .5

C lassification an d in d icatio n s of biologics

C lassification an d in d icatio n s of biologics… … … ...

… … … ...

4 0

2 .5 .1

In trod u ction… … … ....

4 0

2 .5 .2

C lassification of bio lo gics… … … .

4 2

2 .5 .3

In d ica tions of bio logics… … … .

4 5

2 .5 .4

P rev alence of u se of biologics… … … .

4 6

2 .6

B iolog ics u sed in th e treatm en t o f au to im m u n e

B iolog ics u sed in th e treatm en t o f au to im m u n e d isea ses… … … .

d iseases… … … .

5 0

(12)

T able of con tents

_ __ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _

2 .7

B iolog ic im m u n om od u lato rs u sed in th e treatm en t o f

B iolog ic im m u n om od u lato rs u sed in th e treatm en t o f rh eu m ato id arthritis,

rh eu m ato id arthritis,

C roh n ’s d isease a n d m u ltiple sclerosis

C roh n ’s d isease a n d m u ltiple sclerosis … … … …

… … … …

… … …

5 5

2 .7 .1

R h eu m a toid arth ritis (R A )… … …

5 5

2 .7 .1 .1

D efin ition… … … ..

5 5

2 .7 .1 .2

D isease p revalen ce b y age an d gend er… … … .

5 5

2 .7 .1 .3

P ath ogenesis… … … ...

5 6

2 .7 .1 .4

C lin ical p resen tation … … …

5 7

2 .7 .1 .5

D ia gn ostic criteria… … … ...

5 8

2 .7 .1 .6

D esired ou tcom e… … … ...

5 8

2 .7 .1 .7

P h arm a co lo gica l trea tm ent… … … ....

5 9

2 .7 .2

C roh n ’s d isease… … … .

7 3

2 .7 .2 .1

D efin ition… … … ...

7 3

2 .7 .2 .2

D isease p revalen ce b y age an d gend er… … … ..

7 3

2 .7 .2 .3

C lin ical p resen tation … … … .

7 3

2 .7 .2 .4

D ia gn ostic criteria… … … ....

7 4

2 .7 .2 .5

D esired ou tcom e… … … ...

7 4

2 .7 .2 .6

P h arm a co lo gica l trea tm ent… … … ...

7 4

2 .7 .3

M u ltip le sclerosis (M S )… … … .

8 1

2 .7 .3 .1

D efin ition… … … ...

8 1

2 .7 .3 .2

D isease p revalen ce b y age an d gend er… … … .

8 1

(13)

T able of con tents

_ __ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _

2 .7 .3 .4

D ia gn ostic criteria… … … ...

8 2

2 .7 .3 .5

D esired ou tcom e… … … ..

8 2

2 .7 .3 .6

P h arm a co lo gica l trea tm ent… … … ...

8 2

2 .8

A d v erse reaction s, co n tra

A d v erse reaction s, co n tra ----indications a nd drug

A d v erse reaction s, co n tra

in d ication s a n d d rug

in d ication s a n d d rug ----drug interactions of bio lo gic

d rug in teraction s of bio lo gic

im m u n om o d u lators

im m u n om o d u lators… … … ..

… … … ..

9 0

2 .8 .1

In trod u ction… … … ...

9 0

2 .8 .2

A d v erse reaction s… … …

9 0

2 .8 .3

C on tra-in d icatio n s a nd in tera ction s… … … ...

9 3

2 .9

C ost im p a ct of biolo gics

C ost im p a ct of biolo gics … … … ...

… … … ...

9 6

2 .9 .1

In trod u ction… … … ...

9 6

2 .9 .2

G lobal an d regio nal cost im p a ct of biolo gics… … …

9 7

2 .1 0

B iosim ilars: T h e fo llow

B iosim ilars: T h e fo llow ----on biologics

on biologics

on biologics… … … ..

… … … ..

111108

0 8

2 .1 1

L eg islation

L eg islation … … … .

… … … .

111110

1 0

2 .1 2

P h arm a co econ om ic asp e

P h arm a co econ om ic asp ects o f biologic im m u n om od u latin g m ed icin e...… … … …

cts o f biologic im m u n om od u latin g m ed icin e...… … … …

1 1 2

2 .1 2 .1

In trod u ction… … … ...

1 1 2

2 .1 2 .2

P h arm a co eco nom ics… … … .

1 1 2

2 .1 2 .3

P h arm a co eco nom ic asp ects o f biolog ics… … … ...

1 1 3

2 .1 2 .4

P h arm a co eco nom ics app lied to R h eu m atoid arthritis… … …

1 1 4

2 .1 3

C h ap ter su m m ary

C h ap ter su m m ary … … … …

… … … …

… … …

… … … …

1 1 8

(14)

T able of con tents

_ __ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ __ _ _ _ _

C h ap ter 3 :

C h ap ter 3 : M ethodo logy an d E m p irical in v estigation

3 .1

R esearch objectiv es

R esearch objectiv es… … … .

… … … .

… … … . 119

… … … .

1 1 9

3 .1 .1

G en eral research objectiv e… … … …

1 1 9

3 .1 .2

S p ecific research objectiv es… … … ...

1 2 0

3 .2

R esearch d esign

R esearch d esign … … … ..

… … … ..

… … … .. 121

… … … ..

1 2 1

3 .2 .1

D ru g u tilisation rev iew … … … ...

1 2 1

3 .2 .1 .1

R etro spective d rug u tilisatio n rev iew (rD U R )… … … …

1 2 3

3 .3

R esearch m eth odo logy

R esearch m eth odo logy … … … .

… … … .

… … … . 124

1 2 4

3 .3 .1

D ata sou rce… … … ...

1 2 4

3 .3 .2

S tu d y p op u latio n… … … ....

1 2 4

3 .4

D ata an alysis

D ata an alysis … … … …

… … … …

… … …

… … … …

1 2 7

3 .4 .1

C lassification system s… … … .

1 2 8

3 .4 .1 .1

M ed ication… … … …

1 2 8

3 .4 .1 .2

D em ograp h ic p ara m eters… … … .

1 2 9

3 .4 .1 .3

G en eral p aram eters… … … .

1 3 0

3 .4 .2

D escrip tiv e m easu res… … … ..

1 3 1

3 .4 .2 .1

P rev alence… … … .

1 3 1

3 .4 .2 .2