Treat - to - Target Pathway Commissioning Chronic and Complex Care MIDLANDS RHEUMATOLOGY & MUSCULOSKELETAL (MSK) COMMISSIONING NETWORK

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1 Treat - to - Target Pathway Commissioning Chronic and Complex Care MIDLANDS RHEUMATOLOGY & MUSCULOSKELETAL (MSK) COMMISSIONING NETWORK Dr Bruce Kirkham Consultant Rheumatologist Guy s & St Thomas NHS Foundation Trust

2 Disclosures Industry and investigator-initiated studies of therapies for arthritis since 1985, currently Novartis, Lilly Research support: Novartis, UCB, Roche Consultant/Speaker: Abbott, BMS, Chugai, MSD, Novartis, Pfizer, Roche, UCB Guy s and St Thomas Hospitals Schmollinger Map

3 Treat-to-Target in Chronic Disease Management Uncontrolled chronic diseases have serious adverse long-term outcomes, eg, hypertension, diabetes, glaucoma, inflammatory arthritis Control of disease should relieve symptoms now, AND also prevent serious long-term problems Short-term measures to indicate good control should also predict better long-term outcomes, eg, targets for BP, blood sugar, bone turnover Smolen JS, et al. Ann Rheum Dis. 2010;69:

4 Aims of Therapy in RA Treatment of rheumatoid arthritis must be based on a shared decision between patient and rheumatologist Control signs and symptoms, especially reduce pain Prevent joint damage Maintain quality of life and ability to function Reduce risk of mortality from comorbidities such as cardiovascular disease, lymphoma, and interstitial lung disease Smolen JS, et al. Ann Rheum Dis. 2013;0:1-18; Smolen JS, et al. Ann Rheum Dis. 2010;69:

5 Composite Disease Activity Measures Swollen/tender joint count, patient global score, and ESR or CRP DAS28 Scale Severe disease activity DAS remission DAS28 <2.6 DAS44 <1.6 Other composite measures Moderate disease activity Low disease activity Remission SDAI, CDAI, Boolean Other indices of remission Disease activity Normal labs (ESR, CRP) Quality of life Zero disability (HAQ <0.5) X-rays No radiographic progression True remission: absence of symptoms, inflammation, and damage progression van der Heijde D, et al. Ann Rheum Dis. 1990;49:916-20; Prevoo MLL, et al. Arthritis Rheum. 1995;38:44-8; Smolen JS, et al. Rheumatology. 2003;42:244-57; Aletaha D, et al. Arthritis Rheum. 2005;52: ; Aletaha D, Smolen JS. Rheum Dis Clin North Am. 2006;32:

6 SDAI, CDAI, More Stringent Targets Simple Disease Activity Index (SDAI) 28 SJC, 28 TJC, patient global score, physician global score, CRP, simple additive score (no logs!) Clinical Disease Activity Index (CDAI) 28 SJC, 28 TJC, physician global score, patient global score, no ESR Similar to DAS28 with severe, moderate, and low disease activity, and remission boundaries Remission measures are more stringent, fewer people achieve them, but they have significantly better related functional and QoL outcomes Smolen JS, et al. Rheumatology. 2003;42:244-57; Aletaha D, et al. Arthritis Rheum. 2005;52: ; Aletaha D, et al. Arthritis Res Ther. 2005,7:R

7 Algorithm to Treat RA to Target Active RA Main target Adapt therapy according to disease activity Remission Adapt therapy if state is lost Sustained remission Use a composite measure of disease activity every 1-3 months Assess disease activity about every 3-6 months Adapt therapy according to disease activity Low disease activity Adapt therapy if state is lost Sustained low disease activity Alternative target Smolen J, et al. Ann Rheum Dis. 2010;69:

8 The TICORA Study: The First Treat-to-Target (T2T) Study Using DAS Mean DAS Month Routine Group (n=55) Intensive Group (n=55) Intensive, goal-driven therapy achieves better patient outcome than routine therapy 110 patients with active RA treated over 18 months (DAS44 goal <2.4) Patients in intensive-treatment group had monthly objective assessments Sulfasalazine (SSZ) monotherapy triple therapy escalate dosages add prednisone switch to MTX/cyclosporin switch to alternative DMARD IA/IM steroid in intensive group No biologic agents used Grigor C, et al. Lancet. 2004;364:

9 TICORA: T2T vs Routine Care Resulted in Significantly Better Clinical Outcomes at 18-Month Assessment Significant reduction in disease activity with T2T at 3 months, sustained to month 18 P <0.001 P <0.001 Adult patients with highly active RA (mean DAS=4.7) and mean disease duration of 19.5 months. *DAS <2.4 and decline in score from baseline by >1.2; DAS <1.6. Grigor C, et al. Lancet. 2004;364:

10 Median Change TICORA: T2T vs Routine Care Resulted in Significantly Lower Radiographic Progression at 18-Month Assessment P=0.002 P=0.331 P=0.02 Adult patients with highly active RA (mean DAS=4.7) and mean disease duration of 19.5 months. *2 radiologists scored hands and feet radiographs at 0 and 18 mo with van der Heijde modification of Sharp score. Correlation between scores of 2 radiologists tested interobserver variability. Mann Whitney nonparametric analysis. Error bars represent interquartile ranges. Grigor C, et al. Lancet. 2004;364:

11 Challenges of Goal-Directed Therapy in Routine Care Most studies evaluating the T2T strategy (eg, TICORA, CAMERA) have studied patients with early RA and after informed consent has been obtained Are they representative of our normal RA population? How does this affect important patient related outcomes, such as function (Health Assessment Questionnaire, HAQ) or Quality of Life? 11

12 The RA Centre Treat-to-Target aim: DAS28 remission in all patients since 2004 DAS28, function (HAQ), and QoL (EQ-5D) assessed at each visit 12

13 Patients With DAS28 <2.6, % Median HAQ Higher Remission Rates and Better Function With T2T vs Routine Care in Patients With RA Duration Up to 15 Years Improvements in disease control up to 2 years were more pronounced at lower disease duration T2T therapy up to 2 years improved function in patients with disease duration up to 15 y T2T Routine All all P <0.05 *P <0.01 P <0.05 * 5 y 10 y 15 y 30 y Disease Duration 5 y 10 y 15 y 30 y Disease Duration Gullick NJ, et al. Rheumatology. 2012;51:

14 Patients, % T2T Therapy Resulted in Improved Disease Activity While Maintaining Functional Capacity Over 3-Year Follow-up in Patients With Longstanding RA (N=281) Median HAQ, IQR Increasing numbers achieved DAS28 remission (<2.6) over 3 y (P <0.01 vs baseline) Baseline Year 2 In 119 patients who achieved remission at least once, function significantly improved over 3 y Year 1 Year 3 P=0.001 n= HDAS, high disease activity score (DAS); IQR, interquartile range; LDAS, low DAS; MDAS, moderate DAS. Gullick NJ, et al. Ann Rheum Dis. 2011;70(suppl 3):

15 What about Quality of life? As joint damage becomes less severe, quality of Life becomes a key output of patient-related outcomes of effective RA management There are many measures we have used the EQ-5D (EuroQuol) Questions cover 5 domains of life the utility index, plus a VAS of overall health (the thermometer) How does achieving a better DAS28 outcome relate to QoL?

16 Mean value Function and QoL improve with better DAS28 responses in RA (n=123) 2.5 HAQ EQ5D Remission LDAS MDAS HDAS Unpublished data, RA Centre

17 Mean DAS28 COST of T2T? CAMERA-II Course of DAS28 during 2 years of treatment 1 * MTX + placebo MTX + prednisone * Early diagnosis of RA offers the potential to achieve better outcomes with simple therapies, eg steroids and methotrexate Requires regular visits and monitoring in the early stages ie The Best Practice Tariff Pathway (monthly visits initially) A T2T strategy, if used with early arthritis treatment pathways, does not increase use of biologic therapies in routine use Time (Months) RA Centre - largest group in remission are taking Methotrexate only Biologic use in 29.6% of all patients *P <0.001; dotted line = DAS28 remission cut-off. 1. Bakker MF, et al. Ann Intern Med. 2012;156:329-39; 2. Jurgens M. Clin Exp Rheumatol. 2014;32:

18 Conclusions The T2T strategy is now possible in routine clinical practice in early and established RA The T2T strategy increases the number of patients achieving short-term remission with improved long-term outcome: function, QoL, reduction of structural damage progression A T2T strategy, if used with early arthritis treatment pathways, does not increase use of biologic therapies in routine use 18

19 Acknowledgments Dr. Nicola Gullick Laura Blackler, Specialist Nurse Alex Vincent, Database Manager RA Centre Clinicians: Prof. Gabriel Panayi, Dr. Jon Rees, Dr. Alan Mistlin, Dr. Alex Bennett, Dr. Toby Garrood, Prof. Andy Cope Guy s and St Thomas NHS Foundation Trust and King s College London s comprehensive Biomedical Research Centre