1. What is the definition of remission in RA? American Rheumatism Association (ARA)¹ Five or more of the following criteria must be fulfilled for at least two consecutive months: Duration of morning stiffness not exceeding 15 minutes No fatigue No joint pain (by history) No joint tenderness or pain on motion ESR (Westergren method): Female < 30 mm/h, Male < 20 mm/h DAS44² <1.6 DAS28² <2.6 CDAI³ < 2.8 1.Pinals RS, et al. Arthritis Rheum. 1981;24:1308-15. 2. Prevoo. Br J Rheumatol. 1996;35:1101-5. 3. Aletaha D, et al Arthritis Res Ther. 2005;7:R796-R806

2. Criteria for clinical remission Remission LDA Modified ACR criteria 4/5 (pain, TJ, SJ, MS,ESR) DAS ≤ 1.6 ≤ 2.4 DAS28 ≤ 2.6 ≤ 3.2 SDAI (SJ+TJ+PGA+CRP) ≤ 3.3 ≤ 11 CDAI (SJ+TJ+PGA) ≤ 2.8 ≤ 10 Sustained remission Imaging remission MRI, US Complete clinical response (FDA) : remission ≥ 6 months + radiographic arrest Remission in rheumatoid arthritis

3. Remission is Heterogenous Clinical Remission: ACR/DAS criteria, or normal acute phase response, no clinical synovitis Imaging Remission: no significant synovitis on sensitive imaging True Remission: a state of no detectable disease with no progression of structural damage

4. Radiographic progression – Improvement with TNF Targeted Therapies (TEMPO) van der Heijde, et al. Ann Rheum Dis 2006;65(Suppl. II):509 Total sharp score change over 3 years -2 0 2 4 6 012 3 Change from baseline (mean ± SD) MTX ETN ETN + MTX Years * * * †‡ P<0.05 * ETN vs MTX, † combo vs MTX ‡ combo vs ETN

5. TEMPO extension study: DAS28 remission 15% 64% (p<0.05) 56% (p<0.05) 41% 47% 26% 42% 25% 40% ETN + MTX Combination (n=96) MTX add ETN (n=55) ETN add MTX (n=76) Martin Mola E et al. Presented at EULAR 2007. FRI0148.

6. BeSt Treatment Strategies Sequential monotherapy n=126 Step-up combination n=121 Initial combination with prednisone n=133 Initial combination with infliximab n =128

7. Percentage in remission in BeSt sequential monostep-up combination combi with prednisonecombi with infliximab De Vries – Bouwstra Ann Intern Med 2007; 146: 406-15.

8. Results: Summary  At 5 years –48% of patients in DAS remission –10% - 19% of patients in drug-free remission –51 patients previously in drug-free remission had restarted a DMARD Klarenbeek et al. Ann Rheum Dis 2008;67(Suppl II):187