Treating to Target: The Example of RA Presenter Neal S. Birnbaum, MD, FACP, MACR Clinical Professor of Medicine University of California, San Francisco Director, Division of Rheumatology California Pacific Medical Center San Francisco, California Disclosures Learning Objectives Dr. Birnbaum: Promotional speakers bureau AbbVie, Amgen, Janssen, Pfizer; Advisory board Takeda Discuss the most common disease activity and remission indicators in rheumatoid arthritis (RA) Review the literature behind the treat to target movement in RA Recognize the major recommendations of the Smolen treat to target article New Strategies in Therapy for RA Evolution of RA Treatment Small Molecules MTX, Oral gold Anakinra ADA TCZ HCQ, Steroids SSZ D-Pen, AZA Leflunomide IFX ETN Rituximab ABA GLM CZP TFA ASA 19 193s 195s 196s 197s 198s 1998/9 22 28 21 212 Era MTX Era Biologic Era Treat Signs and Symptoms in Established Disease Combination and Biologic Treatment Disease Modification ASA = aspirin; HCQ = hydroxychloroquine; SSZ = sulfasalazine; D-Pen = D-penicillamine; AZA = azathioprine; MTX = methotrexate; IFX = infliximab; ETN = etanercept; ADA = adalimumab; ABA = abatacept; GLM = golimumab; CZP = certolizumab; TCZ = tocilizumab; TFA = tofacitinib.
RA: Application of Clinical Assessment Tools in Practice Classification and Remission Criteria 1987 Revised ACR Classification Criteria for RA Criterion 1. Morning stiffness lasting 1 hour 2. Swelling of 3 joints 3. Swelling of hand joints 4. Symmetric joint involvement 5. Rheumatoid nodules 6. Serum RF 7. Radiographic changes RF = rheumatoid factor; ACR = American College of Rheumatology. Arnett C, et al. Arthritis Rheum. 1988;31(3):315-324. Must satisfy 4 of the 7 criteria Criteria 1 through 4 must have been present for 6 weeks Patients with 2 clinical diagnoses are not excluded 21 ACR/EULAR RA Classification Criteria 21 RA Classification Criteria 1 joint with synovitis (excluding the DIP, first MTP and first CMC joints) Absence of alternative diagnosis that better explains synovitis Achievement of total score of 6 (of 1) from individual scores in 4 domains Joint involvement patterns Serologic abnormality Elevated acute-phase response Symptom duration Swollen/Tender Joints (-5) 1 large joint 2-1 large joints 1 1-3 small joints 2 4-1 small joints 3 >1 joints ( 1 small joint) 5 Serology (-3) Negative RF AND ACPA Low-positive RF OR ACPA 2 High-positive RF OR ACPA 3 Symptom Duration (-1) <6 weeks 6 weeks 1 Acute Phase Reactants (-1) Normal CRP AND normal ESR Abnormal CRP OR abnormal ESR 1 Patients with a score of 6 have definite RA EULAR = European League Against Rheumatism. DIP = distal interphalangeal joint; MTP = metatarsophalangeal; CMC = carpometacarpal; ACPA = anti-citrullinated protein antibody; CPR = C-reactive protein; ESR = erythrocyte sedimentation rate. Aletaha D, et al. Arthritis Rheum. 21;62(9):2569-2581. 21 RA Classification Considerations EULAR Definition of Erosive Disease in RA In addition to those patients who are newly presenting, 3 other groups must be considered: 1. Those with erosions typical for RA were deemed to have prima facie evidence of RA classified as having definite RA 2. Those with longstanding disease either active or inactive who, based on retrospectively available data, can be determined to have previously satisfied the classification criteria classified as having definite RA 3. In the setting of early disease that is being treated, subjects may not fulfill the new criteria at initial presentation, but may do so as their condition evolves over time For use in the 21 ACR/EULAR RA classification criteria Intended to be highly specific (>9%) When an erosion (defined as a cortical break) is seen on radiographs of both hands and feet in at least 3 separate joints at any of the following sites: PIP joints MCP joints Wrist (counted as one joint) MTP joints Aletaha D, et al. Arthritis Rheum. 21;62(9):2569-2581. PIP = proximal interphalangeal; MCP = metacarpophalangeal. van der Heijde D, et al. Ann Rheum Dis. 213;72(4):479-481.
ACR/EULAR 211 Provisional Definition of Remission in RA for Clinical Trials Boolean-Based Definition At any time point, patient must satisfy all of the following: Tender joint count 1 * Swollen joint count 1 * CRP 1 mg/dl Patient global assessment 1 (on a 1 scale) Index-Based Definition At any time point, patient must have SDAI score 3.3 Clinical Measurement Including Patient- Reported Outcomes *Use of 28-joint tender and swollen joint counts may miss actively involved joints (especially in feet and ankles) preferable to include feet and ankles also when evaluating remission. SDAI = Simplified Disease Activity Index. Felson DT, et al. Arthritis Rheum. 211;63(3):573 586. Why Quantify RA Disease Activity? How to Quantify RA Disease Activity Measure burden of disease Assess potential for joint destruction Compare disease activity between visits Assess response to therapy Facilitate treatment-to-target Identify state of remission Clinical composite indices Patient-reported outcome measures ACR response criteria (ACR2/5/7) Disease activity score (DAS and DAS28) HAQ/MDHAQ RAPID3 SDAI RADAI CDAI SF-36 Laboratory tests Acute phase reactants: ESR, CRP Biomarker panels Imaging Plain radiographs Musculoskeletal ultrasound Magnetic resonance imaging DAS = Disease Activity Score; CDAI = Clinical Disease Activity Index; HAQ = Health Assessment Questionnaire; MDHAQ = Multidimensional Health Assessment Questionnaire; RADAI = Rheumatoid Arthritis Disease Activity Index; SF-36 = Short Form-36; RAPID3 = Routine Assessment of Patient Index Data with 3 measures. Keystone EC. J Rheumatol. 21;37(5)883-884. Felson DT, et al. Arthritis Rheum. 1995;38(6)727-735. Anderson J, et al. Arthritis Care Res. 212;64(5):64-647. Zatarain E, et al. Nat Clin Pract Rheumatol. 26;2(11): 611-618. Yazici Y, et al. Bull NYU Hosp Jt Dis. 27;65(suppl 1):S25-S28. Keller SD, et al. Med Care. 1999; 37(5 Suppl):MS1-MS9. What Rheumatologists Measure Outcome Measures: The Debate Physician Responders (%) 9 8 7 6 5 4 3 2 1 15.4 Scored HAQ 34.1 Patient Global VAS 38.3 38.8 Pain VAS 28- Joint Count 83.9 77.1 71.1 12.2 DAS ESR CRP CCP Rationale for using objective outcome measures Successful use of treatment targets in other disease states Blood pressure in hypertension Hemoglobin A1c in diabetes Low-density lipoprotein in hyperlipidemia Uric acid in gout Published studies demonstrating benefit ( treat to target ) A more scientific/objective approach to treating a disease Integration of outcome measures with electronic health records Patient outcomes and/or quality improvement goals CCP = cyclic citrullinated peptide. Surveymonkey 28. Courtesy of John Cush, MD. Bakker MF, et al. Ann Rheum Dis. 27;66(suppl 3):iii56-iii6. Grigor C, et al. Lancet. 24; 364(943):263-269.
Outcome Measures: The Debate ACR Response Criteria Rationale for not using objective outcome measures Perceived increased time requirement Lack of consensus regarding which instrument(s) to use Does quantitative measurement of disease activity in daily practice, as compared to in clinical trials, actually result in better patient outcomes? Integration into electronic health records has been challenging Reported as percent improvement, comparing disease activity at 2 discrete time points ACR2 is 2% improvement ACR5 is 5% improvement ACR5 responders include ACR2 responders ACR7 is 7% improvement ACR7 responders include ACR2 and ACR5 responders Used to maximally discriminate effective treatment from placebo treatment in clinical trials Not directly applicable to clinical practice Felson DT, et al. Arthritis Rheum. 1995;38(6):727-735. DAS DAS28 SDAI CDAI Continuous Measures of RA Disease Activity DAS28: A Simplified DAS Simplified DAS using 28-joint count Integrates measures of physical examination, acute phase response, and patient self-assessment DAS28 =.56 Tender 28.28 Swollen 28.7 ln(esr).14 (Global Health on VAS) Provides absolute indication of RA disease activity on a scale of.49 to 9.7 DAS28 >5.1 = high disease activity DAS28 3.2-5.1 = moderate disease activity DAS28 2.6-3.2 = low disease activity DAS28 <2.6 = remission van Gestel AM, et al. Arthritis Rheum. 1998;41(1):1845-185. Continuous Measures: Disease Activity Indices Clinical Components of Composite Measures SDAI* CDAI* Outcome Measures in RA TJC (-28) TJC (-28) ACR2/5/7 DAS28 SDAI CDAI RAPID SJC (-28) Patient Global Assessment (-1) SJC (-28) Patient Global Assessment (-1) Patient function Patient pain Patient global Physician Global Assessment (-1) CRP (mg/dl) Physician Global Assessment (-1) Eliminates ESR/CRP Physician global # Tender joints # Swollen joints *Both are highly correlated with DAS28, ACR2/5/7, and HAQ ESR or CRP TJC = tender joint count; SJC = swollen joint count. Aletaha D, et al. Clin Exp Rheumatol. 25;23(suppl 39):S1-S18. Yazici Y. Bull NYU Hosp Jt Dis. 27;65(suppl 1):S25-S28. Zatarain E, et al. Nat Clin Pract Rheumatol. 26;2(11):611-618. Pincus T, et al. Rheum Dis Clin North Am. 29;35(4):773-778.
TJC and SJC Central to the clinical assessment of synovitis Outcome upon which therapeutic decisions are based Prominent components of clinical composite indices ACR response criteria DAS and DAS28 SDAI CDAI Contribution of SJC/TJC Impact on Composite Indices ACR response criteria TJC and SJC must improve by 2%, 5%, or 7%, regardless of improvement in 3 of the other 5 score set measures DAS and DAS28 TJC and SJC are 2 of the 4 outcome measures TJC and SJC contribute numerically to 5% of the score TJC is weighted more heavily than SJC SDAI and CDAI TJC and SJC are weighted equally Keystone EC. J Rheumatol. 21;37(5):883-884. Keystone EC, et al. J Rheumatol. 21;37(5):883-884. Patient-Reported Outcome Measures RAPID3 HAQ MHAQ MDHAQ RAPID RADAI Includes 3 patient-reported outcome measures from ACR Core Data Set Patient self-assessed physical function Patient pain assessment Patient global assessment Requires no activity on the part of a health professional, other than to calculate simple arithmetic totals in about 5-1 seconds Provides absolute indication of RA disease activity on a scale of to 3 RAPID3 >12. = high disease activity RAPID3 6.1-12. = moderate disease activity RAPID3 3.1-6. = low disease activity RAPID3-3. = remission Correlates with DAS28 and with CDAI in clinical practice MHAQ = Modified Health Assessment Questionnaire. Pincus T, et al. Rheum Dis Clin North Am. 29;35(4):773-778. RAPID3 Instruments Used to Measure RA Disease Activity 1. Please check ( ) the ONE best answer for your abilities at this time: Without With OVER THE PAST WEEK, ANY SOME With UNABLE MUCH to Do Were You Able to: Difficulty Difficulty Difficulty Dress yourself, including tying shoelaces and doing buttons? 1 2 3 Get in and out of bed? 1 2 3 Lift a full cup or glass to your mouth? 1 2 3 Walk outdoors on flat ground? 1 2 3 Wash and dry your entire body? 1 2 3 Bend down to pick up clothing from the floor? 1 2 3 Turn regular faucets on and off? 1 2 3 Get in and out of a car, bus, train, or airplane? 1 2 3 Walk two miles? 1 2 3 Participate in sports and games as you would like? 1 2 3 2. How much pain have you had because of your condition OVER THE PAST WEEK? Please indicate below how severe your pain has been: NO PAIN AS BAD AS PAIN IT COULD BE.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 1 3. Considering all the ways in which illness and health conditions may affect you at this time, please indicate below how you are doing: VERY VERY WELL POORLY.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 1 Pincus T, et al. J Rheumatol. 28;35(11):2136-2147. FN 1 =.3 16 = 5.3 2 =.7 17 = 5.7 3 = 1. 18 = 6. 4 = 1.3 19 = 6.3 5 = 1.7 2 = 6.7 6 = 2. 21 = 7. 7 = 2.3 22 = 7.3 8 = 2.7 23 = 7.7 9 = 3. 24 = 8. 1 = 3.3 25 = 8.3 11 = 3.7 26 = 8.7 12 = 4. 27 = 9. 13 = 4.3 28 = 9.3 14 = 4.7 29 = 9.7 15 = 5. 3 = 1 PN PTGL RAPID (-3) DAS28 SDAI CDAI RAPID 3 REMISSION <2.6 3.3 2.8 Threshold of Disease Activity LOW MODERATE HIGH 3.2 >3.2 and 5.1 > 5.1 11 >11 and 26 >26 1 >1 and 22 >22 < 6. 3. 6. >6. and 12 >12 DAS28, Disease Activity Score 28 joints; SDAI, Simplified Disease Activity Index; CDAI, Clinical Disease Activity Index; RAPID 3, Routine Assessment Patient Index Data Saag KG, et al. Arthritis Rheum. 28;59(6):762-784; Pincus T, et al. Arthritis Care Res (Hoboken). 211;63(8):1142-1149. Iking-Konert C, et al. Ann Rheum Dis. 211;7(11):1986-199.
EULAR Response Criteria for RA Limitations of Measurement Tools DAS28 at Endpoint Improvement in DAS28 from Baseline >1.2 >.6 and <1.2 <.6 <3.2 Good Moderate None 3.2-5.1 Moderate Moderate None >5.1 Moderate Moderate None Joint assessment TJCs in context of fibromyalgia, nodal osteoarthritis Swollen joints fibrous thickening vs synovitis Patient global: inadequately addresses RA inflammatory activity Frequently includes comorbid symptoms (headache, back pain) Includes nonreversible functional impairment HAQ/MDHAQ allows for irreversible disability (floor effect) Acute phase reactants Even if current measurements available, not always reflective of underlying disease activity van Gestel AM, et al. Arthritis Rheum. 1996;39(1):34-4. Aletaha D, et al. Arthritis Rheum. 26;54(9):2784-2792. Vectra DA Biomarkers: Categories and Primary Role Biomarker Biomarker Category Primary Role VCAM-1 Adhesion molecules Cellular influx EGF VEGF-A Growth factors and tissue expansion IL-6 TNF-RI MMP-1 MMP-3 YKL-4 Leptin Resistin SAA CRP Cytokine-related proteins MMPs Skeletal-related proteins Hormones Acute phase proteins Local inflammation and destruction Cartilage degradation and joint damage Stromal activity and regulation (fibroblasts, chondrocytes, vascular cells) Systemic inflammatory response VCAM-1 = vascular cellular adhesion molecule 1; EGF = epidermal growth factor; VEGF-A = vascular endothelial growth factor; IL-6 = interleukin-6; TNF-RI = tumor necrosis factor-receptor 1; MMP = matrix metalloproteinase; SAA = serum amyloid. Curtis JR, et al. Arthritis Care Res (Hoboken). 212;64(12):1794-183. Vectra DA Is Validated Against DAS28-CRP to Measure RA Disease Activity True Positive Rate The Vectra DA score was significantly associated with disease activity categories based on DAS28-CRP* (P<.1) 1..75.5.25. RF and/or Anti-CCP AUROC =.77*.25.75.. 5 1. False Positive Rate *Low vs moderate/high disease activity using DAS28-CRP = 2.67 as the threshold. AUROC = area under the receiver operating curve. Curtis JR, et al. Arthritis Care Res (Hoboken). 212;64(12):1794-183. True Positive Rate 1..75.5.25. RF- and Anti-CCP- AUROC =.7*..25. 5.75 1. False Positive Rate Assessment of RA Disease Activity in Clinical Practice Data Collection Tools Online DAS28 calculator METEOR (calculates DAS/DAS28/SDAI/CDAI) CORRONA iphone DAS28 calculator application Other CORRONA = Consortium of Rheumatology Researchers of North America.
METEOR METEOR METEOR Foundation. www.meteorapplication.com. Accessed March 13, 213 METEOR Foundation. www.meteorapplication.com. Accessed March 13, 213 METEOR JointMan METEOR Foundation. www.meteorapplication.com. Accessed March 13, 213 JointMan Treat-to-Target
Concept and Background The Value of Tight Control Categorically 3 concepts Choose measurement and measure consistently Identify a target or targets Utilization of the measurement in a defined time frame Study Target Intensive Routine P value BeSt Remission (DAS28 <2.6) 31% 18% <.5 TICORA Remission (DAS < 1.6) 65% 16% <.1 CAMERA Remission = no swollen joints plus 2 out of 3 of the following: Number of painful joints 3 ESR 2 mm/hr 1st VAS general well being 2 mm 5% 37%.29 FIN-RACo Modified minimal disease activity 63% 43%.16 Remission (ACR criteria) 37% 19%.17 Goekoop-Ruiterman YP, et al. Ann Rheum Dis. 21;69:65-69. Grigor C, et al. Lancet. 24;364: 263-269. Verstappen SM, et al. Ann Rheum Dis. 27;66(11):1443-1449. Rantalaiho V, et al. Arthritis Rheum. 29;6(5):1222-1231. Quantitatively-Driven Therapy for Early RA: Clinical Trials TICORA BeSt TICORA: Tight Control for RA Intensive Management Group Monthly review of disease activity and measurement of DAS Structured escalation of therapy if DAS >2.4 after 3 months of a new DMARD SSZ MTX SSZ HCQ MTX (up to 25 mg/wk) SSZ (up to 5 g/d) add prednisolone 7.5 mg/d switch to MTX CSA switch to leflunomide or sodium aurothiomalate IM steroid given as bridge therapy during first 3 months of a new DMARD IA corticosteroid injection of up to 3 swollen joints monthly Routine Care Group Reviewed every 3 months (with no measure of disease activity) Management at discretion of attending rheumatologist (eg, DMARD therapy, IA, IM, oral steroids) TICORA = Tight Control of Rheumatoid Arthritis study; BeSt = Behandel Strategieën study. Grigor C, et al. Lancet. 24;364(943):263-269. Goekoop-Ruiterman YP, et al. Arthritis Rheum. 25; 52(11):3381-339. DMARD = disease-modifying antirheumatic drug; HCQ = hydroxychloroquine; IM = intramuscular; IA = intraarticular. Grigor C, et al. Lancet. 24;364(943):263-269. TICORA: Tight Control for RA Improves Disease Activity after 18 Months of Intensive Management TICORA: Tight Control for RA Improves Outcomes after 18 Months of Intensive Management DAS 6 5 4 3 2 1 Intensive Routine 3 6 9 12 15 18 Month P<.1 vs routine care after month 3 ITT = intent to treat. Grigor C, et al. Lancet. 24;364(943):263-269. Patients Intensive Routine Care Management 1 * 91 * 84 8 * 71 64 6 4 2 4 18 ACR2 ACR5 ACR7 ITT population *P<.1 vs placebo Intensive Group (n=53) Routine Group (n=5) DAS 3.5 ± 1.1 1.9 ± 1.4 HAQ.97 ±.8.47 ±.9 Erosion score.5 ( - 3.375) Joint space 3.25 narrowing (1.125-7.5) Total Sharp score 4.5 (1-9.875) 3 (.5-8.5) 4.5 (1.5-9) 8.5 (2-15.5) Difference (95% CI) 1.6 (1.1-2.1).5 (.2 -.8) P <.1*.25* n/a.2 n/a.331 n/a.2 Data are mean ± SD. *Student s t test used. Median (IQR) increase in score. Mann-Whitney test used. CI = confidence interval. Grigor C, et al. Lancet. 24;364:263-269.
BeSt: Patient Population BeSt: Study Design Multicenter, randomized clinical trial Inclusion criteria Active, early RA 6 of 66 swollen joints 6 of 68 tender joints ESR 28 mm/hour or global health score of 2 mm Seen every 3 months and dose adjusted if DAS 44 2.4 not attained No routine care arm Goekoop-Ruiterman YP, et al. Arthritis Rheum. 25;52(11):3381-339. Group 1 Sequential Mono MTX 15 mg MTX 25 mg SSA Leflunomide MTX IFX n = 49 MTX CsA pred AZA pred Group 2 Step-up Combo MTX 15 mg MTX 25 mg MTX SSA MTX SSA HCQ MTX SSA HCQ pred MTX IFX n = 12 MTX CsA pred Leflunomide Group 3 Initial Combo n = 126 n = 121 n = 133 n = 128 Van der Kooij SM, et al. Ann Rheum Dis. 29;68(7):1153-1158. MTX 7.5 mg/wk SSA pred 6 7.5 mg/day MTX 25 mg SSA pred MTX CsA pred MTX IFX n = 25 Leflunomide AZA pred Group 4 IFX MTX MTX 25 mg IFX 3 mg/kg n = 12 MTX IFX 1 mg/kg SSA Leflunomide MTX CsA pred AZA pred Results from the BeSt Study at 3 Years Algorithm for Treating RA to Target Mean Score 1.6 1.2.8.4 Step-Up Therapy Initial Combination with Prednisone Initial Combination with Infliximab Sequential Monotherapy 1 HAQ DAS Remission (<1.6) 75 Patients (%) 5 25 44% Main Target Active RA Adapt therapy according to disease activity Remission Adapt therapy if state is lost Sustained remission Sharp Score 6 12 18 24 3 36 Time (months) 8 Radiographic Progression 6 4 2-2 2 4 6 8 1 Patients (Cumulative %) Patients (%) 6 12 18 24 3 36 Time (months) 1 Radiographic Progression >SDC 8 P =.4 6 44 43 4 29 25 2 Median* 3.8 3. 1.8 1.5 Mean* 9.5 6.6 3.9 3.3 Alternative Target Use a composite measure of disease activity every 1-3 months Adapt therapy according to disease activity Low disease activity Assess disease activity about every 3-6 months Adapt therapy if state is lost Sustained low disease activity *Increases from baseline in Total Sharp Scores. SDC = smallest detectable change. Van der Kooij SM, et al. Ann Rheum Dis. 29;68(7):1153-1158. Smolen JS, et al. Ann Rheum Dis. 21;69(4):631-637. Clinical Trials vs Real-World Experience: Do Patients in Clinical Trials Reflect What is Seen in the Clinic? DREAM Remission Induction Cohort Study From 26, consecutive newly diagnosed RA patients, made at the discretion of the attending experienced rheumatologist Symptom duration (defined as time from the first reported symptom to the diagnosis of RA by a rheumatologist) of 1 year Patients were included in the study upon diagnosis DAS28 2.6 No previous treatment with DMARDs and/or prednisolone Rheumatology clinics of 5 hospitals in The Netherlands Prospective, nonrandomized, nonblinded cohort type observational study Vermeer M, et al. Arthritis Rheum. 211;63(1):2865-2872.
DREAM Remission Induction Cohort Study: Treatment DREAM: Primary Outcomes Week Number DAS28 Medication Week 2.6 MTX 15 mg/week Week 8 2.6 MTX 25 mg/week Week 12 2.6 MTX 25 mg/week; SSZ 2 mg/day Week 2 2.6 MTX 25 mg/week; SSZ 3 mg/day Week 24 3.2 * MTX 25 mg/week; ADA 4 mg every 2 weeks Week 36 2.6 and MTX 25 mg/week; ADA 4 mg/week decrease of 1.2 Week 52 3.2 * MTX 25 mg/week; ETN 5 mg/week 1 Year, 3 Months 3.2 * MTX 25 mg/week; IFX 3 mg/kg every 8 weeks 1 Year, 6 Months 2.6 MTX 25 mg/week; IFX 3 mg/kg every 4 weeks If DAS 2.6 for 6 months, medications tapered The goal of treatment was remission (DAS28 2.6); treatment was intensified when target was not met * Following the guidelines of the Dutch Society of Rheumatology and Dutch reimbursement regulations, anti-tnf therapy could be prescribed to patients with at least moderate disease activity (DAS28 3.2) and in whom treatment with at least 2 DMARDs had failed (including MTX 25 mg/week; Anti-TNF therapy could be continued only if the DAS28 had decreased by 1.2 after 3 months. SSZ = sulfasalazine. Vermeer M, et al. Arthritis Rheum. 211;63(1):2865-2872. Clinical Outcomes in the Patients after 6 Months of Follow-Up* 6 Months (n = 491) 12 Months (n = 389) 1. DAS28 Level Remission (DAS28<2.6) 231 (47.) 226 (58.1) Low (2.6 DAS28 3.2) 95 (19.4) 57 (14.7) Moderate (3.2<DAS28 5.1) 143 (29.1) 97 (24.9) High (DAS28>5.1) 22 (4.5) 9 (2.3) 2. EULAR Response Good 283 (57.6) 264 (67.9) Moderate 139 (28.3) 93 (23.9) None 69 (14.1) 32 (8.2) 3. ACR Remission 123/384 (32.) 149/321 (46.4) The successful implementation of this treat-to-target strategy aiming at remission demonstrated that achieving remission in daily clinical practice is a realistic goal *Values are the number (%); ACR remission could not be evaluated in all patients due to missing values for morning stiffness. Vermeer M, et al. Arthritis Rheum. 211;63(1):2865-2872. Summary What About Imaging? Newly established 21 ACR/EULAR RA classification criteria and 211 ACR/EULAR definition of remission Allows earlier disease recognition for clinical study and research Implications for clinical practice Clinical trials have demonstrated the benefit of targeted therapies RA disease measurement: allows quantitative baseline measure Key is to use a treatment strategy to continuously strive to push disease toward improvement Advance therapy in stepwise fashion while continuously measuring disease to achieve goal or as close as is reasonably feasible Not currently part of most disease activity and treat to target measures May be ultimate measure of disease control and inhibition of structural damage Plain X-Ray Ultrasound Long-time standard for imaging. Readily available Moderate cost Requires serial studies to assess degree of disease control Sharp score or other quantitative grading usually done only in clinical trials Radiographic progression may occur despite clinical remission Low cost, no radiation, portable in-office procedure Better for assessing synovitis than clinical exam Useful for both diagnosis and guidance for arthrocentesis Reliability is operator dependent Lillegraven S, et al. Ann Rheum Dis. 212;71(5):681-686. Karim Z, et al. Arthritis Rheum. 24;5(2):387-394. Nakagomi D, et al. Arthritis Rheum. 213; 65(4):89-898.
Ultrasound in Rheumatologic Practice (German US Score) MRI Wrist Fingers Toes Ability to identify early erosions before X-ray Synovitis Paratenonitis/ Tenosynovitis Ulnar Ulnar PD PD PD PD PD PD MCP II, III PIP II, III MCP II, III PD only PD PD only PD PD PD MTP II, V PD Significance of early lesions is not always clear Can identify inflammation in many RA patients in clinical remission or low disease activity state Erosions MCP II, III, MCP II Radial PIP II, III, MTP II, V, Plantar MTP V Lateral 1 Joint 4 Joints 2 Joints 7 Joints Gray-scale US and power Doppler US synovitis, tenosynovitis/paratenonitis, and erosions from dorsal, palmar, and ulnar aspects of wrist, MCP, PIP and MTP joints. Backhaus M, et al. Arthritis Rheum. 29;61(19):1194-121. Gandjbakhch F, et al. J Rheumatol. 211;38(9):239-244. Conclusions Better treatments for RA have resulted in higher expectations for control of signs and symptoms, better function, and long-term remission or low disease activity Quantitative disease activity measures combined with treat-to-target methodologies can lead to better longterm outcomes Constrained health care dollars and accountable care mandates will accelerate the movement to document high value care with better outcomes, lower cost and improved patient satisfaction Questions & Answers