Gout Goals Are Not Being Achieved!! Strengthening The Provider/Patient Alliance Featuring PEPtools TM JointsAflame

Transcription

1 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance QS Priorities Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Paul P. Doghramji, MD, FAAFP Family Physician Collegeville Family Practice Medical Director of Health Services Ursinus College Collegeville, PA QS Priorities 1. Patient Safety: Making care safer by reducing harm caused in the delivery of care 2. Patient and Caregiver Engagement: Ensuring that each person and family are engaged as partners in their care 3. Coordination of Care: Promoting effective communication and coordination of care 4. Dissemination of Best Practices: Promoting the most effective prevention and treatment practices for the leading causes of mortality 5. Population and public health: Working with communities to promote wide use of best practices to enable healthy living 6. Efficient use of healthcare resources: Making quality care more affordable for individuals, families, employers, and governments by developing and spreading new health care delivery models How Do You Achieve Goal? Patients and Providers View Gout Differently 1. Know gout- and place it on the practice radar 2. Know that treating an acute attack is EVER enough 3. Know that getting SUA < 6mg/dL (< 5mg/dL with tophi) is THE GAL 4. Know that >25% of patients will need combinations of meds to achieve goal Providers view gout medication adherence as good - providing excellent relief In actuality, gout medication adherence is poor Less than 36% Patients discontinue gout meds Patients think ULT worsens or has no impact on gout Do not recognize long-term value DC therapy due to clinical and cost concerns Patients don t understand the concept of treatment goal Reach G. Joint Bone Spine. 2011;78: Harrold LR, et al. Chronic Illn : Coburn BW et al. Target Serum Urate- Do Gout Patients Know their Goal? 2016 Arth Care Res68(7): DC, discontinue ULT, urate lowering therapy Gout and The Patient Significant morbidity Work-related disability Loss of productivity Increase healthcare costs All-cause hospital admissions Diet Recommendations Weight loss or 5%-10% goal Reduce or eliminate alcohol Drink lots of water and/or other non-alcoholic fluids Increase low- or non-fat dairy Increase plant-based proteins Beans, legumes Avoid high-purine foods rgan meats ily fish Asparagus/cauliflower Mushrooms Rimler E, Lom J, Higdon, Cosco D, Jones D. A Primary Care Perspective on Gout 2016 pen Urol & eph Journ: 9, (Suppl 1:M5) ACR Recommendations and Healthline MEDX Detroit ovember 11,

2 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance The Economics behind Achieving Gout Goals Year Study Authors Title Factor Cost 2013 Rao S, Haji A, Burns L, Choi H 2015 Rai SK, Lindsay CB, De Vera MA, Haji A, Giustini D, Choi HK 2016 Lim Sy, Lu, za A, Fisher M, Rai SK, Menendez ME, Choi HK The Economic Burden of Gout: A Systematic Review of Direct and Indirect Costs (Boston U. and Univ. of British Columbia) The Economic Burden of Gout: A systematic review -Work productivity loss with >3 flares/yr -Gout related healthcare costs with 6+ flares/yr All-cause direct costs Employed Elderly Treatmentrefractory $ 2,000+ per patient $ 12,000+ per patient Gout on-gout $ 4,400 $ 2,560 $ 17,000 $10,600 $ 18,400 $ 7,200 Trends in Gout & -Inflation-adjusted $ 58,003 Rheumatoid Arthritis Hosps. annual hospitalization In the US costs for gout (+68%) Gout admissions Preventableinadequate or inefficient care Knowledge Gaps in Patients Clear understanding of progression Recurrent flares result in chronic joint damage Treatment options and duration of therapy for acute and chronic gout Concept of ULT to avoid complications and disability Treatment goals Khanna P et al. Knowledge Gaps In Patients with Gout- A Qualitative Study ACR/ARHP Annual Meeting. Coburn BW et al. Target Serum Urate- Do Gout Patients Know their Goal? 2016 Arth Care Res68(7): Patient Engagement Accountability starts with an informed patient Improves patient satisfaction with therapy decision Promotes adherence to therapeutic regimen and medication Patient Education Goals in Gout Patients want to know more 1 Causes of gout Treatment goals Long-term consequences Exercise for overall health, joint mobility, and weight maintenance 2 Diet Medication adherence tips 1. nna M, Hinsenveld E, de Vries H, Boonen A. Health Literacy in patients dealing with gout Clin Rheumatology 34(9): Physical Activity Goals CDC 2015 Arthritis improves with physical activity Adult goals 150 minutes moderate-intensity/ week plus Muscle strengthening 2 or more days/week lder adult goals minutes moderate-intensity/ week plus Muscle strengthening 2 or more days/week Physical disability Refer to physical therapist ACR: Diet Recommendations Avoid Limit Encourage rgan meats high in purine content non-fat dairy products Serving sizes of: Low-fat or (sweetbreads, liver, kidney) Beef, Lamb, Pork Seafood with high purine content B B B (sardines, shellfish) Servings of naturally High fructose corn syrup - sweetened sweet fruit juices Vegetables, Cherries sodas, other beverages, or foods Table sugar, and sweetened beverages and desserts Table salt, including in sauces C and gravies C C Alcohol overuse (defined as more than 2 Alcohol (particularly beer, but also wine servings per day for a male and 1 serving and spirits) in all gout patients per day for a female) in all gout patients B B Any alcohol use in gout during periods of frequent gout attacks, or advanced gout under poor control C CDC 2015 Gout Goals MEDX Detroit ovember 11,

3 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance The Patient - Achieving Gout Goals All of these points are welltaken, but how do we engage patients to change by understanding their goals and becoming ACTIVATED? Why is SDM Valuable? Enhances provider patient relationship and communication nly 4 of 10 Medicare patients feel their preferences are considered 1 Improves medication adherence 2 Understand risk/benefit Know value of therapy Decreases costs of care 3 Fewer unnecessary tests performed Improves patient satisfaction with therapy 4 1 Covinsky KE, et al. J Am Geriatr Soc. 2000;48(5 Suppl):S187-S Ratanawongsa, et al. JAMA Intern Med. 2013;173: shima LE, et al.. Engl J Med. 2013;368: Barry MJ, et al. Engl J Med. 2012;366: Shared Decision-Making Shared Decision-Making Process A process by which providers and patients make health care decisions together Aligns medical care with patient preferences and values A core tenet of patient centered care and quality improvement SDM required for Medicare Shared Savings Shared decision-making aids crucial to decision process Whoa way too much information! Provider Medical evidence and information Therapeutic options Patient-friendly terms Patient eeds, values, preferences for therapy Decision Care plan Follow-up SDM Tool SDM Aid: Interactive MEDX Detroit ovember 11,

4 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Patient Education Websites Gout and the Provider Gout and Uric Acid Education Society Most cases of gout are treated in the primary care setting 1 Recent survey found opportunities for gout management and treatment 2 Education re achievement of gout goals Implement office monitoring SUA (serum uric acid) Comorbidities ULT re comorbidities CFIDETIAL FR ITERAL USE LY 1. Becker MA, Schumacher HR, Romain PL Treatment of Acute Gout; 2016 UpToDate; UpToDate.com 2. Zychowicz M, Howson A, Kim D. et al. Improving gout management in primary care AAFP ational Conference Poster. Where Does Urate Come From? Gout Risk Factors About two-thirds of uric acid is generated endogenously by the body, while one-third comes from purines in the diet 1 Purine Catabolism 2-4 o Uricase in Humans and Higher Primates Advancing age Male gender Family history of gout besity Certain drugs: diuretics, low dose aspirin, cyclosporin Alcohol, especially beer and binge drinking Lead toxicity rgan transplants Thyroid problems ther serious illness 1 Fam AG. J Rheum. 2002;29: ; 2 Hediger MA, et al. Physiology. 2005;20: ; 3 Johnson RJ, et al. J Comp Physiol B. 2009;179:67-76; 4 Terkeltaub RA. In: Primer on the Rheumatic Diseases. 12 th ed. Atlanta, GA: Arthritis Foundation; 2001: Singh JA, Reddy SG, Kundukulam J. Risk Factors for Gout and Prevention 2011 Curr pin Rheum 23(2): Diagnosing Gout nly 50% of Gout patients have a dedicated office visit or are treated in first 6 months Common S&S Joint swelling Intense pain in one or two joints Pain free times between attacks Uric Acid Levels Low or normal during attack >6.0 Imaging X-rays, CT Scan, Ultrasound Joint damage Joint Aspiration Urate crystals Zhang W, et al. Ann Rheum Dis. 2006;65: Differential Diagnosis Rule out other conditions Pseudogout Calcific tendinitis Septic arthritis Psoriatic arthritis, spondyloarthropathy steoarthritis of the first MTP joint or with nodal A of small hand joints Rheumatoid arthritis Cellulitis Lyme disease Trauma ACR, American College of Rheumatology EULAR, European League Against Rheumatism A, osteoarthritis Joint Aspiration: Ideal vs Practical Ideal Provides definitive diagnosis Reality Joint fluid is aspirated only in ~10% of gout cases in primary care; diagnosis is made by the clinical presentation Presumptive Triad of acute monoarticular arthritis, hyperuricemia, and dramatic response to colchicine Recommendations If there is reasonable doubt about the diagnosis, aspirate the joint (or refer for aspiration), especially if septic arthritis suspected ACR Clinical Symposia: Developing ACR Guidelines for the Treatment of Gout ACR/ARHP Annual Scientific Meeting. ov 8, 2011;Chicago, IL. MEDX Detroit ovember 11,

5 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Comorbidities in Gout Individuals in the US general population with gout and hyperuricemia have significantly higher comorbidities 1 Comorbidities Gout- Hyperuricemia o Gout- o Hyperuricemia Hypertension besity Diabetes ephrolithiasis Myocardial infarction Heart Failure Stroke Renal Impairment Zhu Y, et al. Am J Med Jul;125: e1. CKD Associated With Gout 71% of US patients with gout have stage 2 or higher CKD 1 Annual reduction in GFR Healthy adults ml/min Untreated hyperuricemic adults 2.5 ml/min/1.73 m2 1 Martillo M, Karis E, Crittenden db, Pillinger MH Gout Co-Morbidities: Prev. and Mgmt Future Med Clinical Guidelines Underutilized in Gout nly 52.8% of PCPs provide optimal medication therapy for acute gout attacks <20% of PCPs recommended optimal Tx for tophaceous gout <20% of PCPs use ULT with dose titration and prophylaxis Acute and Chronic Gout Therapy is Suboptimal Anti-inflammatory drugs for gout attacks underdosed Patients dissatisfied and non-adherent as a result Long-term ULT value to prevent joint destruction not understood by patients or providers Harrold LR, et al. Rheumatology. 2013;6: Edwards L. Curr Rheumatol Rep. 2011;13: ACR: Therapy and Prevention of Acute Flares Gouty arthritis attack (acute flare) Reduce pain, inflammation, and disability quickly Treat with pharmacologic therapy within 24 hours of onset Treatment for Acute Gouty Inflammation First-line options 1-3 In 2008, the FDA withdrew SAIDs* IV colchicine from the market due to ral Colchicine inappropriate use and deaths. Glucocorticosteroids* Intra-articular Parenteral* Combinations if severe or refractory 1 Terkeltaub RA. Eng J Med. 2003;349: Terkeltaub R. at Rev Rheumatol. 2010;6: Terkeltaub RA, et al. Arthritis Rheum. 2010;62: *Refer to package insert for adverse events and safety data MEDX Detroit ovember 11,

6 Subjects with at Least ne Flare in a 4-week period (%) Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Medication Considerations for Acute Flare Treatment Risk of GI bleeding (SAID use) Cardiovascular disease (SAID use) Kidney health (SAID and colchicine use) Diabetes (systemic steroid use) Gout Flare Risk Increases With ULT Expect gout flares with all ULT strategies, especially in first 6 months of treatment Remain on ULT during flares Flares indicate effective ULT due to tophus remodeling Manage flares Initiate prophylaxis 1-2 weeks before starting ULT Important: unexpected flares decrease compliance with ULT - educate patient! Becker MA, et al. Eng J Med. 2005;353: Gout Flares: Febuxostat vs Gouty arthritis flares peak when prophylactic colchicine is stopped at 8 weeks Day 1 - wk Period Febuxostat, 120 mg Febuxostat, 80 mg, 300 mg Subjects Requiring Treatment for Gout Flares The percentage of subjects in each interval is calculated by dividing the number of subjects with at least one gout flare in that interval by the number of subjects exposed to at least one dose of drug in that interval. Subjects may be counted in more than one interval. Subjects received prophylaxis during the period from day 1 to week 8. Results for 80 mg febuxostat group are shown in red, those for 120 mg febuxostat group in blue, and those for 300 mg allopurinol group in green. Becker MA, et al. Eng J Med. 2005;353: Treating Gout Flares: Key Points When you start therapy is more important than which agent you use (ACR recommends 24 hours) Select agent considering patient comorbidities The sooner treatment is initiated after symptoms begin, the faster it will work When taken at the earliest hint of a flare, attacks may be aborted with one dose Wortmann PL, et al. Gout and hyperuricemia. In: Harris ED Jr, et al, eds. Kelly s Textbook of Rheumatology. 7 th ed. Philadelphia, PA: WB Saunders Company; 2005: Flare Management: SAIDS Flare Management: Colchicine Take as soon as symptoms begin, such as Ibuprofen* aproxen* Indomethacin* Determine the correct dose with the patient Should not be used in: 1 Gastric bleeding Renal failure Heart failure Gastric AE s 2 Proton pump inhibitor may be given *Refer to package insert for adverse events and safety data ral colchicine used in two situations: Acute Flare Dose adjustment in CKD and/or drug interaction, unless lack of tolerance or medical contraindication Flare Prophylaxis Colchicine 0.6 daily or bid for 3-6 months or longer ote: Chronic use of colchicine among gout patients linked with a decreased risk of myocardial infarction 1 Winzenberg T, et al. J Fam Pract. 2009;58(7):E Laine L. Rev Gastroenterol Disord. 2003;3 Suppl 4:S30-S39. AE s, adverse events Khanna D, et al. Arthritis Care Res. 2012;64: CKD, chronic kidney disease MEDX Detroit ovember 11,

7 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance ral Colchicine Dosing Guidelines for Acute Gout Colchicine 0.5 mg TID daily for 1-3 days AGREE trial: Large, randomized, double-blind, placebo-controlled trial (n=184 patients treated for early gout flares [<12 hours]) 2 Low-dose colchicine 1.2 mg, and then 0.6 mg 1 hour later (1.8 mg total), equally effective and better tolerated than high-dose colchicine 1.2 mg, then 0.6 mg hourly x 6 hours (4.8 mg total) (P<0.05) 1 Zhang W, et al. Ann Rheum Dis. 2006;65: Terkeltaub RA, et al. Arthritis Rheum. 2010;62: Treat to Goal Serum Urate Lowering Goal Serum urate level should be lowered sufficiently to prevent gout attacks Target <6.0 mg/dl at a minimum Target <5.0 mg/dl if tophi or still getting attacks if <6.0 In Europe, target is <5.0 Pharmacologic Urate-lowering Strategies Uricosuric-Probenecid Uricosuric Increase uric acid elimination: eg, target proximal tubule epithelial cell transporters using probenecid Uricostatic Suppress uric acid formation: eg, target xanthine oxidase using allopurinol or febuxostat Uricolytic biologic approach Directly degrade soluble urate: pegloticase Terkeltaub R. at Rev Rheumatol. 2010;6: ne of two FDA-approved agents currently available Typical dosing: 500 mg BID titrated up to 2.5 g a day Usage First line if XI can t be used Second line: added to XI if target not reached ot effective with egfr <50 1 Reinders MK, et al. Ann Rheum Dis. 2009;68: Contraindicated with uric acid overproduction Activity blocked by ASA Side effects common 1 Urolithiasis risk onspecific GI, CS side effects Rash, drug-drug interactions XI, xanthine oxidase inhibitor egfr, estimated glomerular filtration rate ASA, aspirin Uricosuric-Lesinurad SURI (selective uric acid reabsorption inhibitor) Approved as add-on therapy ow available in pharmacies Lesinurad: Selective Uric Acid Reabsorption Inhibitor CLEAR 1 and CLEAR 2 Primary End Point Proportion of subjects achieving serum uric acid <6 mg/dl at month 6 (%) LESU200 vs PB (CLEAR 1 and CLEAR 2 combined): RR = 2.15; 95% CI: 1.78, 2.59 LESU400 vs PB (CLEAR 1 and CLEAR 2 combined): RR = 2.46; 95% CI: 2.05, 2.95 t = P <.0001 vs PB + ALL arm CLEAR 1 CLEAR 2 PB + ALL 28 t 23 LESU200 + ALL 54 t 55 t LESU400 + ALL 59 t 67 t PB, placebo Saag KG, et al. Lesinurad, a novel selective uric acid reabsorption inhibitor, in two phase III clinical trials: Combination Study of Lesinurad in Standard of Care Inadequate Responders (CLEAR 1 and 2) ACR Abstract L10. MEDX Detroit ovember 11,

8 Proportion of patients achieving sua <6mg/dL at Month 6 Proportion of patients achieving sua <6mg/dL at Month 6 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Lesinurad- Increase in Patient Achieving sua <6 mg/dl at Month 6 Lesinurad Efficacy in Patients with Mild or Moderate Renal Impairment- Consistent with verall Trial Population 60% 50% 54% 55% 70% 60% 57% 59% 40% 30% 20% 28% 23% Placebo + ALL Lesinurad ALL P< % 40% 30% 20% 29% 32% Placebo + ALL Lesinurad ALL P< % 10% 0% CLEAR 1 (n=603) Lesinurad Prescribing Information; Ironwood. CLEAR 2 (n=610) 0% 60- <90 ml/min 45- <60mL/min Baseline renal function Lesinurad Prescribing Information; Ironwood. Lesinurad- Safety Information Risk of acute renal failure- more common when used without a XI Lesinurad should be used in combination with a XI Lesinurad Dosing ne 200mg tablet daily in combination with an XI, including allopurinol or febuxostat Requires no dose adjustment for: Mild or moderate renal impairment (eclcr >45 ml/min) Mild or moderate hepatic impairment 65 years and older Lesinurad PI. Ironwood Uricosurics: thers Losartan, fenofibrate, atorvastatin: all off label Good added options in hyperlipidemia and hypertension if indicated Relatively weak effects Uricostatic Medications Xanthine oxidase inhibitor (XI) therapy - First Line urate lowering therapy (ULT) Febuxostat MEDX Detroit ovember 11,

9 Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Available in US since 1966 Purine-like backbone, converted in liver to oxypurinol Hypoxanthine Xanthine Uric acid xypurinol ormal half-life 24 hours Renal Elimination Starting dosage of allopurinol should be no greater than 100 mg/day and less than that in moderate to severe CKD Gradual upward titration of the maintenance dose, which can exceed 300 mg daily even in patient with CKD Dosing Guidelines Most common ULT in US Pruritic rash in ~2%; intolerance in 5%-10% (eg, hepatic enzyme elevation, GI, CS) Major cutaneous reactions (SJS, TE) linked with HLA-B58 Major allopurinol hypersensitivity syndrome has incidence of 0.1%-0.4%, up to 25% mortality Riedel AA, et al. J Rheumatol. 2004;31: Chao J, et al. Curr Rheumatol Rep. 2009;11: Terkeltaub R. Recent Advances in Difficult-to-Treat Gout: Medscape ACR 2008 Annual Mtg; San Francisco, CA. GI, gastrointestinal CS, central nervous system SJS, Stevens-Johnson syndrome TE, toxic epidermal necrolysis ACR, EULAR and FDA Guidelines Start at 100 mg daily, lower in CKD Increase by 100 mg daily every 2 weeks until the target SUA level is reached ~400 mg daily is an average dose to achieve target level in subjects with preserved renal function Divide allopurinol dose to BID at >300 mg daily dose adjustment required in CKD FDA approved at doses up to 800 mg daily (monitor for toxicity) Chao J, et al. Curr Rheumatol Rep. 2009;11: Zhang W, et al. Ann Rheum Dis. 2006;65: Initiating Prior to initiation of allopurinol HLA-B* 5801 screening - risk management High risk ratio Korean with stage 3 or worse CKD Han Chinese Thai Febuxostat: onpurine Xanthine xidase Inhibitor onpurine backbone, selective inhibitor of xanthine oxidase H Primarily metabolized in the liver H C Febuxostat S CH 3 C2H HLA-B*5801, human leukocyte antigen Febuxostat prescribing information. MEDX Detroit ovember 11,

10 Mean change egfr from BL, ml/min Gout Goals Are ot Being Achieved!! Strengthening The Provider/Patient Alliance Febuxostat Phase 3 Trials vs ontitrated : Primary Endpoint Serum Urate <6 mg/dl Febuxostat Dosing Study CFIRMS 1 (6 months) Febuxostat 40 mg daily 45% (n=757) APEX 2 (6 months) -- FACT 3 (12 months) -- Febuxostat 80 mg daily 67% *, ** (n=756) 76% * (n=267) 53% * (n=256) 300 mg daily Placebo 42% (n=755) -- 41% *** (n=268) * P<.001 vs allopurinol ** P<.001 vs febuxostat 40 mg and placebo *** P<.001 vs placebo 1% (n=134) 21% (n=253) -- Label: 40 mg daily for 2 weeks. If serum urate does not normalize after 2 weeks, increase to 80 mg daily Dose reduction not needed in moderate renal or liver impairment (CrCL >29 ml/min) Most common side effects: rash (~2%), elevated LFTs (up to 3%), and arthralgia (~1%) 1 Becker MA, et al. Arthritis Res Ther. 2010;12:R63. 2 Schumacher HR, et al. Arthritis Rheum. 2008;59: Becker MA, et al. Eng J Med. 2005;353: LFTs, liver function tests Preservation of Renal Function with Febuxostat Time, y Expected Decline, untreated hyperuricemia All Subjects treated with febuxostat Combining ULT to Reduce Serum Uric Acid When serum urate target has not been met with appropriate dosing of XI Combination of oral ULT with 1 XI agent and 1 uricosuric agent is appropriate Adapted from Whelton A, et al. Postgrad Med. 2013;125(1): Getting to Goal: Combining Urate Lowering Therapies Many on XI s do not achieve <6 mg/dl or <5 mg/dl Medical need for additional options Consideration may be given to combination therapies Managing the Gout Patient Long-Term Prevent gout attacks with prophylaxis flare therapy for first 3-6 months of ULT Maintain normal serum UA with long-term ULT medication Support diet and lifestyle modifications Monitor side effect status of flare medication Measure UA levels Monitor ULT side effects Monitor renal function UA, uric acid MEDX Detroit ovember 11,