- Rheumatoid arthritis causes joint inflammation, damage and disability if left untreated. It affects around 1% of the population. - Early, aggressive treatment is important to prevent long-term joint damage and disability. Combination treatments, including disease-modifying antirheumatic drugs (DMARDs) and corticosteroids, work better than monotherapy. - The introduction of biologic DMARDs that target cytokines like tumor necrosis factor (TNF) have greatly improved treatment outcomes compared to conventional DMARDs alone. Combining biologics with methotrexate is more effective than biologics alone.

1. L. Essaadouni
Congrès de la SMMI
Fès
Septembre 2017

2.  Autoimmune disease
 Prevalence ~1% of population
 Joint inflammation, swelling, pain,
dysfunction, and disability
 Cartilage and bone destruction
 Co-morbidities+++

3. Pincus, et al. Rheum Dis Clin North Am. 1993;19:123–151.
• Damage occurs early in most patients
• 50% show joint space narrowing or erosions in the
first 2 years
• By 10 years, 50% of young working patients are
disabled
• Death comes early
• Multiple causes
• Compared to general population
 Women lose 10 years, men lose 4 years

6. S. Venuturupalli, MDImmunol Allergy Clin N Am 2017

7.  Induire et maintenir la rémission
 Prévenir les dégâts structurels
 Eviter le handicap fonctionnel
 Eviter les complications: CVX, ostéoporose…
 Réduire la sur mortalité

8. MTX
Etanercept
Infliximab Anakinra
1980
1999
2000
Rituximab
Abatacept
2006
Tocilizumab
Certolizumab
Golimumab
Denosumab
2009-2011

9. Traitements de fond non biologiques Traitements biologiques (bDMARD)
Traitements conventionnels
(csDMARD)
Anti-TNF
Traitement synthétique ciblé
(tsDMARD)
Autres traitements biologiques

10. Nom Cible thérapeutique
Méthotrexate antagoniste du métabolisme de l’acide folique
Leflunomide
inhibiteur sélectif de la synthèse des
pyrimidines
Sulfasalazine
implique possiblement aussi l’adénosine et
l’inhibition du facteur nucléaire kappa B (NF-
kB)
Hydroxychloroquine ?
En combinaison thérapeutique

11. Jose U. Bulletin of the Hospital for Joint Diseases 2013;71(3):204-7

13. Corticoïdes
- Systémiques
- Intra
articulares
- En
combinaison
avec les
DMARD‘s
DMARD‘s
En monothérapie
Biologiques
En combination
avec MTX
Ou en
monothérapie
En combinaison

14. Traiter tôt
Traitement initial intensif
Les combinaisons thérapeutiques
La monothérapie
L’immunogénécité
La place de la corticothérapie

15. Fenête d’ opportunité au début

16. Wiles NJ, et al. Arthritis Rheum 2001; 44: 1033 - 42
0.0
0.5
1.0
1.5
2.0
2.5
3.0
DegreeofDisability*
after5Years
<6 months
(n = 60)
6-12 months
(n = 47)
>12 months
(n = 76)
0.9
2.4
2.3

17. F.Espinoza et al. Ther Adv Musculoskel Dis 2016

18. Boers M et al. Lancet. 1997;350:309-318.
PooledIndex
SSZ alone
SSZ with
MTX + Pred
MTX 7.5 mg/week
Weeks
16 280
0.0
0.4
0.8
1.2
1.6
Prednisolone 7.5 mg/day
Prednisolone
60 mg/day
SSZ 2000 mg/day

19. P =0.008
0
10
20
30
40
0 1 2 3 4 5Years
COBRA:
5.4
points/year
SSZ alone:
8.6
points/year
Landewe RB et al. Arthritis Rheum 2002:46:347-356
SSZ alone
SSZ vs.
COBRA

20. D. L Scott, BMJ 2015

21. D. L Scott, BMJ 2015

22. PERMIER trial
Comet trial
ASPIRE trial
BEST trial
MTX + Adalimumab vs.
either drug alone
MTX + Etanercept vs.
either drug alone
MTX + infliximab vs.
MTX alone
4 treatment strategies
including
MTX + infliximab
St. Clair et al. Arthritis Rheum 2004, 50:3432
Klareskog et al. Arthritis Rheum 2004, 50:238
Emery P et al. Lancet. 2008;372:375-382
Goekoop-Ruiterman et al. Arthritis Rheum 2005, 52:3381

23. Breedveld FC, et al. Arthritis Rheum 2006;54:26-37
23*
21
25* 25
43*
49*
0
10
20
30
40
50
60
Adalumimab
+ MTX
Adalumimab
alone
MTX
alone
Ptsw/DAS28<2.6(%)
Wk 52
Wk 104
*P <.001 ADA + MTX alone and ADA alone.

24. ETN + MTX
(n=274)
Period 1
ETN
(1b)
MTX
(2b)
104 wk
Randomise
(n=542)
Placebo ETN + MTX
(n=268)
52 wk
ETN + MTX
(1a)
ETN + MTX
(2a)
Period 2
Emery P et al. Lancet. 2008;372:375-382.

25. DAS28
Remission
*P<0.0001; LOCF
DAS28 remission=DAS28 <2.6;
DAS44 remission=DAS<1.6; DAS28 LDA=≤3.2;
DAS LDA=DAS<2.4
28% 28%
41%
49%50% 51%
64%
73%
0
20
40
60
80
100Patients(%)
MTX (n=263)
ETN + MTX (n=265)
* *
DAS28
LDA
DAS44
Remission
DAS44
LDA
*
*
Emery P et al. Lancet. 2008;372:375-382.

26. 67%
49%
28%
86%
71%
48%
0
20
40
60
80
100
ACR20 ACR50 ACR70
Patients(%)(mITT)
MTX (n=243)
ETN + MTX (n=256)
*P<0.0001; LOCF
*
*
*
Emery P et al. Lancet. 2008;372:375-382.

27. 2.4
4
0.27
0
0.5
1
1.5
2
2.5
3
ChangefrombaselineinmTSS
MTX
(n=230)
ETN + MTX
(n=246)
Emery P et al. Lancet. 2008;372:375-382.

28. Cs DMARD en combinaison> Cs DMARS en monothérapie
Cs DMARDS en combinaison= Anti-TNF
Anti TNF+ MTX> Anti TNF
Anti TNF+ MTX> MTX

29. A-Infliximab
B-Adalimumab
C- Etanercept
D- Golimumab
E- Tocilizumab

31. 13 compared a biological
agent in monotherapy with
placebo
 14 compared a biological
agent monotherapy to MTX
 one study (ADACTA)
compared two biological agents
S.Tarp et al. Seminars in Arthritis and Rheumatism 2016

32. S.Tarp et al. Seminars in Arthritis and Rheumatism 2016

33. S.Tarp et al. Seminars in Arthritis and Rheumatism 2016

34. T. Schaeverbeke. Rheumatology 2016;55:210220

36. I.Arstikyte, BioMed Research International 2015

37. T. Schaeverbeke. Rheumatology 2016;55:210220

38. T. Schaeverbeke. Rheumatology 2016;55:210220

39. Chi Chiu Moka EXPERT OPINION ON BIOLOGICAL THERAPY, 2016

40. T. Pincus et al. Neuroimmunomodulation 2015;

41. Bjorn Svensson, ARTHRITIS & RHEUMATISM2005,
Objective. To assess the efficacy of low-dose prednisolone on joint
damage and disease activity in patients with early rheumatoid arthritis .
Methods. At the start of their initial treatmentwith a disease-modifying
antirheumatic drug (DMARD), patients with early (duration <1 year)
active RA were randomly assigned to receive either 7.5 mg/day
prednisolone or no prednisolone for 2 years

42. Bjorn Svensson, ARTHRITIS & RHEUMATISM2005,

47. F. Espinoza, Ther Adv Musculoskel Dis 2016, Vol. 8(4) 107–118