Breaking News in Malattie del Ricambio

Transcription

1 Paolo Cavallo Perin Dipartimento di Scienze Mediche Università di Torino Breaking News in Malattie del Ricambio Modena, 1 ottobre 2015

2 Breaking News Malattie del Ricambio 1. Terapia dislipidemie: evolocumab 2. Terapia del DM-2: inerzia clinica

3 Breaking News Malattie del Ricambio 1. Terapia dislipidemie: evolocumab 2. Terapia del DM-2: inerzia clinica

4 Sabatine MS et al. N Engl J Med 372: ,2015 Boston, Iowa City, Houston, Jacksonville, Cincinnati, Johannesburg, Cape Town Amgen, Thousand Oaks, CA

5 Background (1) Hypercholesterolemia is a major risk factor for CVD. Statins are recommended as first-line therapy for CVD management. Other LDL-C lowering agents are needed because some patients: - can not tolerate statins due to adverse events - have extremely high baseline LDL-C levels - have very high risk of CVD events

6 Background (2) Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors (LDLR), facilitates the degradation of LDLRs and leads to LDL-C increase. Inhibiting PCSK9 by monoclonal antibodies, small interfering RNA, and small molecule inhibitors lower LDL-C levels. Evolocumab, a fully human monoclonal antibody that inhibits PCSK9, achieves approximately a 60% reduction in LDL-C levels at the doses used in phase 3 trials.

7 Ferdinand KC and Nasser SA, Cardiovasc Drugs Ther, online June 12, 2015

8 Combined results of the OSLER-1 and OSLER-2 trials (parent trials), two multicentric, open-label, randomized, controlled studies. 12 months. N = 4465, randomly assigned 2:1 to: - evolocumab + standard therapy (evolocumab group) or - standard therapy alone (standard-therapy group). No placebo Evolocumab: s.c. 140 mg every 2 weeks or 420 mg once a month. Sabatine MS et al. N Engl J Med 372: ,201

9 Sabatine MS et al. N Engl J Med 372: ,2015

10 Primary end point Incidence of adverse events. Secondary end point Change in the LDL cholesterol level and other lipids. Prespecified exploratory outcome incidence of adjudicated cardiovascular events (death, coronary events, cerebrovascular events) Sabatine MS et al. N Engl J Med 372: ,201

11 No neutralizing antibodies against evolocumab were detected. Sabatine MS et al. N Engl J Med 372: ,2015

12 LDL-cholesterol levels Sabatine MS et al. N Engl J Med 372: ,2015

13 Changes in other lipids evolocumab group vs standard-therapy group Total cholesterol - 36% (P<0.001) Non-HDL cholesterol - 52% (P<0.001) Apolipoprotein B - 47% (P<0.001) Triglycerides - 13% (P<0.001) Lipoprotein(a) - 25% (P<0.001) HDL cholesterol + 7% (P<0.001) Apolipoprotein A1 + 4% (P<0.001) Sabatine MS et al. N Engl J Med 372: ,2015

14 Sabatine MS et al. N Engl J Med 372: ,2015

15 Rischio CV residuo dopo trattamento con statine Ipertensione obesità diabete LDL non controllato HDL basse età TG elevati fumo Pregressa malattia CV Familiarità per CHD

16 Breaking News Malattie del Ricambio 1. Terapia dislipidemie: evolocumab 2. Terapia del DM-2: inerzia clinica

17 Khunti K et al. Diabetes Care 36: , 2013

18 ADERENZA, PERSISTENZA E COMPLIANCE Aderenza la misura in cui l assunzione dei farmaci, l osservanza di una dieta e/o di nuovi stili di vita corrisponde alle raccomandazioni condivise con il medico. Aderenza terapeutica = persistenza + compliance Persistenza = continuità nell assunzione del farmaco da parte del paziente (misurata come tempo dall inizio del trattamento al suo completamento o interruzione) Compliance = grado di adesione di un paziente all assunzione del farmaco. Percentuale di Uso del Farmaco (Medication Possession Ratio-MPR, numero di giorni di disponibilità del farmaco diviso per il numero di giorni di osservazione; numero di pillole residue al termine del periodo di osservazione. WHO. Prevention and management of osteoporosis. World Health Organ Tech Rep Ser. 2003;921:1-164.

19 ADERENZA AI FARMACI PER IL DIABETE REVISIONE SISTEMATICA Prevalenza dell aderenza nei vari studi OAD: Antidiabetici orali; MPR: Medical Possession Ratio; MMAS-4, Morisky Medication-Taking Adherence Scale-MMAS (4-item): Scala Morisky di aderenza all assunzione del farmaco (4 voci) Krass I, Schieback P, Dhippayom T. Adherence to diabetes medication: a systematic review. Diabet Med Nov 29 [Epub ahead of print]

20 Background (1) The prevalence of DM-2 is high and is increasing. DM-2 is a progressive disease that requires stepwise intensification of treatment to maintain good glycemic control. Timely treatment of people with DM-2 has a beneficial effect on outcomes, i.e. development or progression of micro- or macrovascular complications. People with DM-2 often do not reach recommended glycemic targets (ADA, EASD, NICE).

21 Background (2) Despite several drugs are today available for DM-2, many patients remain in poor blood glucose control. This failure to intensify treatment in a timely manner has been termed clinical inertia. Data are lacking on clinical inertia in the diabetes management pathway in a real-world primary care setting.

22 OBJECTIVE To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs and associated levels of glycemic control. RESEARCH DESIGN This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April Khunti K et al. Diabetes Care 36: , 2013

23 Median time for 1 additional OAD (ys) HbA1c (%) Taking 1 OAD Taking 2 OAD Khunti K et al. Diabetes Care 36: , 2013

24 Median time for introducing INSULIN (ys) Taking 1 OAD Taking 2 OAD Taking 3 OAD Khunti K et al. Diabetes Care 36: , 2013

25 Mean HbA1c (%) at intensification with an OAD or insulin Taking 1 OAD Taking 2 OAD Taking 3 OAD Khunti K et al. Diabetes Care 36: , 2013

26 L inertia per l aggiunta di un altro OAD è stata di circa anni; per l aggiunta di insulina è stata di circa 6.5 anni; è avvenuta in pazienti con HbA1c di %. Khunti K et al. Diabetes Care 36: , 2013

27 ADA EASD Position Statement Diabetes Care 2015;38:

28 Not only patient education, but also, doctor education! H. Keen, 1978

29