Presentation is loading. Please wait.

Presentation is loading. Please wait.

Treat to Target, Role of Orencia in Achieving the target. Prof. Hassan El-Shahaly Professor of Rheumatology and Rehabilitation Suez Canal University ELAR.

Similar presentations


Presentation on theme: "Treat to Target, Role of Orencia in Achieving the target. Prof. Hassan El-Shahaly Professor of Rheumatology and Rehabilitation Suez Canal University ELAR."— Presentation transcript:

1 Treat to Target, Role of Orencia in Achieving the target. Prof. Hassan El-Shahaly Professor of Rheumatology and Rehabilitation Suez Canal University ELAR congress, Alexandria 2013

2 Rheumatoid Arthritis Challenges Complex, multifactorial pathogenesis Fluctuating clinical course; unpredictable prognosis Characterized by: – Progressive joint destruction – Loss of physical function – Poor quality of life

3 CLASSIFICATION CRITERIA FOR RA

4 Rationale 1987 AC R criteria Elaborated in established RA Considered as classification criteria Lack of sensitivity in early disease Current trends in RA Recognize the patients as soon as possible Treat the patients as soon as the diagnosis is made investigate new drugs/strategies at an early stage of the disease ACR /EULAR classification criteria for RA

5 5 Early treatment reduces disability 5 years later according to: Wiles NJ, et al. Arthritis Rheum 2001; 44: 1033 - 42 * Odds ratio of HAQ ≥1 0.0 0.5 1.0 1.5 2.0 2.5 3.0 Degree of Disability* after 5 Years <6 months (n = 60) 6-12 months (n = 47) >12 months (n = 76) 0.9 2.4 2.3

6 Objectives To recognise the disease at an early stage. To develop a set of rules to be applied in newly patients with undifferentiated synovitis Identify the subset at high risk of chronicity & erosion Be used as a basis for initiating disease modifying therapy ACR /EULAR classification criteria for RA Aletaha D, et al. Ann Rheum Dis 2010 ; 69:1580-8 ; Arthritis Rheum 2010;62:2569-81

7 2009 ACR / EULAR for the classification & diagnosis of rheumatoïd arthritis Aletaha D, et al. Ann Rheum Dis 2010 ; 69:1580-8 ; Arthritis Rheum 2010;62:2569-81 * van der Heidje D et al Ann Rheum Dis 2013 Feb 7 Joint involvement(0-5) 1 large joint0 2-10 large joints1 1-3 small joints (large joints not counted) 2 4-10 small joints (large joints not counted) 3 > 10 joints (at Least one small joint) 5 Sérology (0-3) RF négative ET ACPA négative0 RF low level (1 à 3 x ULN ) OR ACPA low level (1 à 3 x ULN) 2 RF high level(> 3 x ULN) OR ACPA high level (> 3 x ULN) 3 Symptoms duration (0-1) < 6 weeks 0 ≥ 6 weeks 1 Acute Phase reactants (0-1) CRP normal AND ESR normal 0 CRP abnormal OR ESR abnormal 1 RA: score ≥ 6 ≥ 1 1 swollen joint Not best explained by another disease Yes No yes New criteria for RA Fulfilled? New criteria for RA Fulfilled? No RA RA Typical RA erosion on X-ray*

8 MANAGEMENT

9 Prevention / arrest of joint damage Prevention / reversal of disability Prevention of systemic co-morbidities: CV diseases, osteoporosis…. Prevention of systemic co-morbidities: CV diseases, osteoporosis…. Sustained Remission Management of patients with RA Therapeutic objectives Remission

10 Therapeuticstrategy Predictive factors of severity Drugs : benefit / risk ratio Disease activity Patient characteristics * age, comorbidities…. * Patient expectations Rheumatoid arthritis: Selection of therapeutic strategy

11 RECOMMENDATION 1: Therapy with synthetic DMARDS should be started as soon as the diagnosis of RA is made RECOMMENDATION 2: Treatment should be aimed at reaching a target of remission or low disease activity as soon as possible in every patient; as long as the target has not been reached, adjustment of the treatment should be done by frequent and strict monitoring. RECOMMENDATION 3: Methotrexate should be part of the first treatment strategy in patients with active RA. EULAR RECOMMENDATIONS FOR THE MANAGEMENT OF RA WITH SYNTHETIC AND BIOLOGICAL DMARDs Smolen J. et al.Ann Rheum Dis 2010;-69:964-75 Combe et al. Ann. Rheum. Dis. 2007; 66: 34-45

12 Turning recommendations into optimal treatment strategies 12 Early referral Early referral Starting biologic agents Starting biologic agents Treat to target Treat to target Short & long -term goals Short & long -term goals Tight control using composite measures Tight control using composite measures Consider poor prognostic factors Consider poor prognostic factors Early institution of DMARDs Early institution of DMARDs Pre- determined treatment targets Pre- determined treatment targets Remission or LDAS as soon as possible Remission or LDAS as soon as possible Maximising HRQOL for the long-term Maximising HRQOL for the long-term Shared decision between doctor and patient Shared decision between doctor and patient Rheumatol- ogists are primary carers Rheumatol- ogists are primary carers

13 Newer RA Treatment Strategies Intensive management Treat to Target Combination DMARD strategies Remission induction

14 Aggressive Strategies Monotherapy with frequent switches – Sawtooth (Fries) Classical step-up (pyramid) – MTX+SSZ+HO-Chl (O’Dell) – MTX+Leflunomide – Others Step-down – COBRA

15 Combination Step-Down Therapy: COBRA Trial Boers M et al. Lancet. 1997;350:309-318. Step-down therapy SSZ alone Step-down (MTX + SSZ + Pred) SSZ MTX 7.5 mg/week Weeks 16280 0.0 0.4 0.8 1.2 1.6 Prednisolone 7.5 mg/day Prednisolone 60 mg/day SSZ 2000 mg/day Pooled Index

16 Systematic literature review: from 1995 to 2008  M eta-analysis of 6 studies Tight control and predefined strategy Schipper LG et al Rheumatology 2010;49:2154-64 00,20,40,60,81,01,21,41,61,82,0-0,2-0,4 Tight control without predefined protocol Fransen, 2005 Fransen, 2003 Van Tuyl, 2008 Tight control without predefined protocol Tight control with predefined protocol Verstappen, 2007 Goekoop, 2009 Grigor, 2002 0,25 (IC 95 : 0,03-0,46) 0,97 (IC 95 : 0,64-1,3) Mean difference in DAS28 change Randomised effect model

17 Traditional DMARDs Are Effective but Do Not Maintain Long-term Response Retention Rates of DMARDs Cumulative Retention Rates 01224364860728496108120 100 90 80 70 60 50 40 30 20 10 0 Methotrexate Sulfasalazine Chloroquine Parenteral Gold Oral Gold Penicillamine Azathioprine Cyclosporine Combination Legend: Time (Months)

18 Taking steps to improve clinical outcome Smolen J, et al. Ann Rheum Dis 2010;69:631–637. 18 Active RA Main target Alternative target Adapt therapy according to disease activity Remission Adapt therapy according to disease activity Low disease activity Use a composite measure of disease activity every 1–3 months Adapt therapy if state is lost Sustained remission Adapt therapy if state is lost Sustained low disease activity Assess disease activity about every 3–4 months Main long- term target Alternative long-term target EULAR RECOMMENDATIONS

19 Phase I of EULAR RA Management Algorithm 19 Smolen JS, et al. Ann Rheum Dis 2010;69:964–75 *The treatment target is clinical remission or, if remission is unlikely to be achieved, at least low disease activity

20 Phase II of EULAR RA Management Algorithm 20 *The treatment target is clinical remission or, if remission is unlikely to be achieved, at least low disease activity Smolen JS, et al. Ann Rheum Dis 2010;69:964–75

21 Phase III of EULAR RA Management Algorithm 21 Smolen JS, et al. Ann Rheum Dis 2010;69:964–75 *The treatment target is clinical remission or, if remission is unlikely to be achieved, at least low disease activity

22 Tracey D, et al. Pharmacology & Therapeutics 117 (2008) 244–279. Different Biologics for RA

23 23 APCAPC Down-regulation of T cell Adapted from Kremer JM. J Clin Rheumatol. 2005;11:S55–S62. CD28 T cell T cell CTLA-4 binding: down-regulation of T cell Upstream T-cell Modulation with ORENCIA® (abatacept) CTLA-4 APCAPC CD28 MHC APCAPC T-cell receptor ORENCIA ORENCIA inhibits T-cell activation by binding to CD80 and CD86. The relationship of these biologic response markers to the mechanisms by which ORENCIA exerts its effects in rheumatoid arthritis (RA) is unknown. T cell T cell

24 Forest plot of risk ratios for clinical remission RR 1.74; 95% CI (1.54, 1.98) no heterogeneity I 2 0%; p = 0.496 Efficacy of initial MTX vs MTX + biological agent in Early RA Kuriya B et al. Ann Rheum Dis online first april 26, 2010

25 Forest plot of risk ratios for radiographic remission RR 1.30; 95% CI (1.01, 1.68) Significant heterogeneity I 2 0%; p = 0.001 Efficacy of initial MTX vs MTX + biological agent in Early RA Kuriya B et al. Ann Rheum Dis online first april 26, 2010

26 CLINICAL TRIALS FOR ABATACEPT

27 AGREE study design: patients with early RA and poor prognostic factors* 1. Westhovens R, et al. Ann Rheum Dis 2009;68:1870–1877; 2. Bathon J et al. Ann Rheum Dis. 2011;70:1949–1956. 27 Inclusion criteria Early RA (≤2 years) MTX-naïve RF+ and/or anti-CCP2+ ≥1 erosion Co-primary endpoints DAS28 (CRP) <2.6 Total Genant-modified Sharp score Double-blind period 1 Open-label period 2 1:1 Randomisation Screening Abatacept + MTX** (n=256) Placebo + MTX** (n=253) 232 227 Abatacept + MTX DAS28 (CRP) X-Ray progression HAQ-DI 433 **MTX initiated at 7.5 mg/week at study entry, then increased to 15 mg at Week 4 and up to 20 mg at Week 8 until study completion; Dose reduction to 15 mg/week was permitted due to toxicity or intolerability; AGREE=Abatacept study to Gauge Remission and joint damage progression in MTX naïve patients with Early Erosive RA; CCP2+=cyclic citrullinated peptide positive. Day 1Year 1Year 2 *Abatacept is not indicated in the EU for the treatment of early RA in MTX-naïve patients. AGREE (MTX-naïve)

28 Significantly greater proportion of abatacept-treated patients achieved DAS28 remission at Year 1* Westhovens R, et al. Ann Rheum Dis 2009;68:1870–1877. 28 p<0.001 41.4% 23.3% *Abatacept is not indicated in the EU for the treatment of early RA in MTX-naïve patients. Data are based on an ITT population, with patients who discontinued considered non-responders. 0 10 20 30 40 50 60 70 80 90 100 Proportion of patients achieving DAS28 remission (%) Abatacept + MTX (n=256) Placebo + MTX (n=253) AGREE (MTX-naïve)

29 Abatacept provides sustained efficacy through 2 years in patients with early RA (≤2 years)* Bathon J, et al. Ann Rheum Dis. 2011;70:1949–1956. 29 Visit day Abatacept plus MTX (n=232)MTX alone (n=227)MTX alone switched to abatacept plus MTX (n=227) *Abatacept is not indicated in the EU for the treatment of early RA in MTX-naïve patients. Data are based on a modified ITT population, including patients who entered the open-label period and patients who discontinued considered non- responders. 0 10 20 30 40 50 60 70 80 90 100 0 29 85 141 197 253 309 365 449 553 617 729 Year 1 Abatacept added to MTX alone group Proportion of patients achieving DAS28-CRP remission (%, 95% CI) 46.1% 26.9% 44.5% 55.2% AGREE (MTX-naïve) Early referral Early referral

30 0.84 0.65 1.75 1.48 BaselineYear 1Year 2 Mean change from baseline in Sharp total score ∆=0.25 Yr 1–2 ∆=0.18 Yr 1–2 ∆ =0.66 BL-Yr 1 p<0.001 for ∆Yr 1–2 vs ∆ BL–Yr 1 Patients with X-rays at all timepoints (n=207) 1.0 Adding abatacept to MTX slows the rate of radiographic progression* Bathon J, et al. Ann Rheum Dis. 2011;70:1949–1956. 30 0.0 2.0 Visit day Abatacept plus MTXMTX aloneMTX alone switched to abatacept plus MTX *Abatacept is not indicated in the EU for the treatment of early RA in MTX-naïve patients. Data are as-observed for patients treated in the open-label period. Abatacept added to MTX alone group AGREE (MTX-naïve)

31 Abatacept leads to sustained HAQ normalisation (≤0.5) over 2 years in half of treated patients* Bathon J, et al. Ann Rheum Dis. 2011;70:1949–1956. 31 Abatacept + MTX (n=232) MTX alone (n=227) MTX alone switched to abatacept + MTX (n=227) *Abatacept is not indicated in the EU for the treatment of early RA in MTX-naïve patients. Data are as-observed for all patients who entered the open-label extension. 0 10 20 30 40 50 60 70 80 90 100 Year 1 Proportion of patients achieving HAQ normalisation (%) Year 2 AGREE (MTX-naïve)

32 32 Efficacy and Safety of Abatacept or Infliximab Versus Placebo ATTEST Trial A Phase III, Multicenter, Randomized, Double-blind, Placebo- controlled Trial on the efficacy and safety of abatacept or Infliximab versus placebo in Patients with Rheumatoid Arthritis and an Inadequate Response to Methotrexate

33 Primary Objective –To study the efficacy of Abatacept in reduction of disease activity in comparison to placebo as measured by disease activity score (DAS) 28 (ESR) at 6 months (day 197) –Determine ACR 20, 50, and ACR 70 response rates for subjects treated with placebo, abatacept, or infliximab at 6 months and 12 months Schiff M, et al. Ann Rheum Dis 2008;67:1096–103 ATTEST the primary endpoint was not designed to be a head-to-head comparison between Abatacept and infliximab.

34 Abatacept + MTX and infliximab + MTX ACR20 response rates are similar at Month 3 34 ATTEST l The onset of action of infliximab was generally more rapid than abatacept however, by day 85, ACR 20 responses are similar Schiff M, et al. Ann Rheum Dis 2008;67:1096–103

35 Further improvement from Month 6 to 12 was observed with abatacept + MTX in ACR 20 response l The onset of action of infliximab was generally more rapid than abatacept up to Day 85 l By Day 365, ACR 20 responses were higher with abatacept than with infliximab (ACR 20: 72.4 vs 55.8%, difference of 16.7 [95% CI: 5.5, 27.8]) 35 ATTEST Schiff M, et al. Ann Rheum Dis 2008;67:1096–103

36 36 ACR Responses at 6 Months ITT population; D/C =Non responders *p<0.001; † p<0.05 and ‡ p<0.01; Χ square test; p-values represent active drug versus placebo The study was conducted in RA patients with inadequate response to MTX and was not designed to demonstrate non-inferiority or superiority of ORENCIA vs infliximab ATTEST Schiff M, et al. Ann Rheum Dis 2008;67:1096–103

37 37 ACR responses at 12 months ATTEST ITT population; D/c =Non responders The study was conducted in RA patients with inadequate response to MTX and was not designed to demonstrate non-inferiority or superiority of ORENCIA vs infliximab Schiff M, et al. Ann Rheum Dis 2008;67:1096–103

38 Abatacept+MTX Delivered Sustained Improvements in ACR Responses Over 2 Years 38 Visit (month) Infliximab patients switched to abatacept ACR Responders (%) Open label LTE period DB period 89% (83,94)* 69% (61,77)* 55% (46,64)* 43 (35,52)* 24% (16,31)* 31% (23,39)* 87% (80,93)* 84% (78,91)* 71% (63,79)* 61 (52,70)* 41% (32,50)* 45% (36,54)* Data are for patients who entered the open-label period, and had data available at the considered time point (as-observed analysis) Treatment groups represent treatment received during the double-blind period *95% confidence intervals Schiff M and Bessette L Clin Rheum 2010 ; 29: 583-519 9 Abatacept+MTX Infliximab 3mg/kg + MTX to abatacept ATTEST-LTE

39 ABATACEPT SHORT & LONG -TERM EFFICACY

40 Abatacept provides similar short-term efficacy at 6 months compared with other biologic agents Placebo-adjusted analysis, based on ACR50 responses Mixed populations included: – MTX-IR – DMARD-IR – Anti-TNF-IR All biologic agents showed significantly greater efficacy compared with placebo, except anakinra 40 Singh JA, et al. Cochrane Database Syst Rev 2009;4:CD007848. Favours PlaceboFavours Biologic Abatacept Adalimumab Anakinra Etanercept Infliximab Rituximab GLIMMIX: Odds Ratio (95% CI) 0.11.010 COCHRANE META-ANALYSIS Studies included only approved dosages.

41 Abatacept short-term efficacy is similar to other biologic agents in real life Yazici Y, et al. Arthritis Rheum 2011; 63(Suppl 10):S873. Abstract 2233. Cumulative incidence of time to RAPID≥3.6 response* (%) Month 0 20 40 60 80 0612302418 Abatacept Etanercept Adalimumab Infliximab 0126543 *Adjusted for age and duration of disease. Prospective patient data from the Arthritis Registry Monitoring Database in patients receiving abatacept (n=114), etanercept (n=148), infliximab (n=38) and adalimumab (n=85). 3,574 encounters were reviewed for this analysis. A total of 385 treatment courses were determined. 272 of the 385 courses represent the only biologic medication used by an individual; 40 individuals used two biologic medications at different times, while 11 had used three biologics.

42 Conaghan P, et al. Ann Rheum Dis 2011;70(Suppl 3):151 Abatacept leads to reductions in synovitis and structural damage by Month 4 – MRI data SynovitisOsteitisErosion Adjusted mean change (95% confidence interval) -1.9 -0.3 0.5 -2.0 0.0 1.0 -3.0 2.0 3.0 0.4 1.5 1.0 Abatacept + MTX (n=25) Placebo + MTX (n=23) MRI (OMERACT RAMRIS) scores from baseline to Month 4 in MTX-IR patients treated with abatacept + MTX or placebo: synovitis of the wrist; osteitis and erosion scores of wrist and hand.

43 Improvements with abatacept seen via sonographic monitoring Personal communication, Walter Grassi. 43 16 Months M.E. 51 year old man with RA Disease duration: 3 years Rheumatoid factor: positive Anti-CCP Ab: positive DAS28: 6.9 Finger pain: VAS 6 16 months later: DAS28: 2.4 Finger pain: VAS 0 Conclusion: Excellent responder

44 LONG TERM GOAL ACHIEVEMENT BY ABATACEPT

45 An increasing proportion of abatacept patients show sustained LDAS or DAS28 remission over 7 years Westhovens R, et al. Ann Rheum Dis 2009;68(Suppl3):577. Poster SAT0108. 45 Responders (%) Year 00.5 0 30 20 10 40 50 70 60 80 100 90 1234567 48.2% (37.4, 58.9) n/N=40/83 25.3% (15.9, 34.7) n/N=21/83 69.7% (54.0, 85.4) n/N=23/33 51.5% (34.5, 68.6) n/N=17/33 Response (95% CI) Remission LDAS DAS28 CRP-defined remission = DAS28 <2.6; LDAS=DAS28 (CRP) ≤3.2. Data are based on all patients originally randomised to 10 mg/kg abatacept who entered the LTE, with data available at the visit of interest (as-observed analysis). Mean disease duration was 9.9 (10.1) years. Double-blind phase Open-label LTE phase

46 Abatacept has demonstrated increasing reductions in rate of structural damage progression through Year 5 Schiff M, et al. Rheumatology 2011;50:437–449; Orencia SmPC November 2011; Data on file; Genant HK, et al. Ann Rheum Dis 2008;67(Suppl 2):193. *Mean change in TS from year to year. Data are for those patients who entered the open-label period, and had evaluable radiographs available at the appropriate time points. Treatment groups represent treatment received in the double-blind period. TS=Total Score AIM (MTX-IR) Mean change from baseline in Genant-modified sharp scores (TS) Year 1 *0.80 *0.26 *0.34 *0.37 *0.41 *1.48 *0.29 *0.43 *0.68 *0.74 46

47 Sustained improvement in physical function with abatacept over 5 years (HAQ-DI response) Schiff M and Bessette L. Clin Rheum 2010;29:583–591. 100 50 40 30 90 80 70 60 00.51.03.55.03.02.52.01.54.04.5 20 0 74.2% (69.0, 79.4) 71.8% (67.2, 76.4) Double-blind phase Open-label LTE phase Data are based on all patients originally randomised to abatacept who entered the long-term extension, with data available at the visit of interest (as- observed analysis). HAQ-DI response ≥ 0.3. Responders (%) Year AIM (MTX-IR)

48 1. Vander Cruyssen B, et al. Arthritis Res Ther 2006;8:R112; 2. Moreland LW, et al. J Rheum 2006;33:854–861; 3. Weinblatt M, et al. Ann Rheum Dis 2006;65:753–759; 4. Data on file; 5. Hetland ML, et al. Arthitis Rheum 2010;62:22–32. Subjects remaining at the end of 4 years of LTE n/N% Infliximab 1 295/51162% Etanercept 2 429/58174% Adalimumab 3 147/26256% Abatacept 4 * (IM101102) 394/53973% Abatacept has a retention rate that is comparable with or higher than the anti-TNF agents Retention may be considered as a surrogate marker of long-term efficacy for biologic agents 5 *Summation of the original abatacept plus placebo treatment groups who entered LTE. Data from literature search on the long-term efficacy results from open-label extension studies of anti-TNFs (in MTX-naïve and MTX-IR patients). 48 LT- RCT

49 Abatacept: Safety Issues Acute infusion reactions 9.8% vs 6.7% placebo, mild-moderate Malignancy & Infection outcomes 4134 Abatacept-treated patients compared with 41,529 DMARD treated patients in 5 cohorts No increased rates of malignancy, infection over 6 years. a Sibilia J, Westhovens R. Safety of T-cell costimulation modulation with abatacept in patients with rheumatoid arthritis. Clin Exp Rheumatol 2007;25 (5Suppl46):S46-56. b Simon TA et al. Malignancies In RA Abatacept clinical development program. ARD 2008.

50 RA Safety Population Cumulative (Double-Blind and Open-Label) Open-Label, Uncontrolled N = 2,339 N = 2,688 PlaceboAbatacept N = 1,955 (204) ) Double-Blind, Controlled (Biologic Background) N = 989 (134) BLA/4M QG

51 Overview of Patients with Adverse Events Double-Blind, Controlled Study Periods AEs SAEs Discontinuation due to AEs Deaths Abatacept N = 1955 1736 (88.8) 266 (13.6) 107 (5.5) 10 (0.5) Placebo N = 989 840 (84.9) 122 (12.3) 39 (3.9) 6 (0.6) Number (%) of Patients

52 Total Patients with Infections Upper Respiratory Tract Infection NasopharyngitisSinusitis Urinary Tract Infection InfluenzaBronchitis 1051 (53.8) 248 (12.7) 248 (12.7) 225 (11.5) 225 (11.5) 125 (6.4) 125 (6.4) 113 (5.8) 113 (5.8) 111 (5.7) 111 (5.7) 101 (5.2) 101 (5.2) 478 (48.3) 119 (12.0) 90 (9.1) 68 (6.9) 68 (6.9) 45 (4.6) 45 (4.6) 52 (5.3) 52 (5.3) 45 (4.6) 45 (4.6) Most Common Infections (≥ 5%) Double-Blind, Controlled Study Periods Preferred Term Abatacept N = 1955 Placebo N = 989 Number (%) of Patients

53 Total Patients with Serious Infections Pneumonia Cellulitis Urinary Tract Infection Bronchitis Diverticulitis Pyelonephritis Acute Sepsis Serious Infections (≥ 0.2%) Double-Blind, Controlled Study Periods 58 (3.0) 9 (0.5) 5 (0.3) 4 (0.2) 3 (0.2) 1 (<0.1) 19 (1.9) 5 (0.5) 2 (0.2) 1 (0.1) 0 3 (0.3) Preferred Term Abatacept N = 1955 Placebo N = 989 Number (%) of Patients

54  Relative Risk to general population: 1.9 [1.7 – 2.1]  Best predictors:  RA severity / disease activity  Age  Corticosteroid therapy  Comorbid diseases: CVD, CHF, CRF, DM, lung disease  Previous infection  Joint surgery  Contributory role of DMARDs not clearly defined Moreland et al. J Rheum 2001;28:1238-44. Predictors and Risk of Infection in Rheumatoid Arthritis

55 Tuberculosis Cumulative Study Periods 2 cases of presumed tuberculosis with abatacept – Tuberculous Infection (Double-Blind): Presented with cervical lymphadenitis; diagnosis based on histology – Pulmonary Tuberculosis Suspected (Open-Label) Presented with dry cough, fever, diaphoresis and crepitus; diagnosis based on clinical presentation and chest radiograph 1 case of presumed tuberculosis with placebo – Tuberculosis - Suspect (Double-Blind): Unknown presentation; no definitive diagnosis

56 Malignancy

57 Continued use of abatacept does not increase the risk of malignancy over time Hochberg M, et al. Arthritis Rheum 2010;62(10Suppl):S164–5. Abstract 390. 57 Integrated safety summary NMSC=non-melanoma skin cancer; Data over a 7-year period; Data lock December 2009. 12,132 p–y of exposure (N=4,149). Clinical trial experience Short term (2,331 p–y) Long term (9,752 p–y) Cumulative (12,132 p–y) PlaceboAbatacept Malignancies, incidence rate (95% CI) Malignancies (excluding NMSC) 0.59 (0.19–1.37) 0.69 (0.39–1.11) 0.74 (0.58–0.93)0.73(0.58–0.89) Lymphoma– 0.04 (0.00–0.24) 0.08 (0.04–0.16)0.07(0.03–0.14) Total solid organ (combined) 0.59 (0.19–1.37) 0.60 (0.33–1.01) 0.60 (0.45–0.77)0.59(0.46–0.75) Lung cancer– 0.21 (0.07–0.50) 0.13 (0.07–0.23)0.15(0.09–0.23) NMSC 0.82 (0.33–1.70) 0.82 (0.49–1.28) 0.74 (0.58–0.93)0.73(0.58–0.90)

58 58 Malignancies: Double-Blind studies Malignant Abatacept: 29 (1.5%) Placebo: 11 (1.1%) Non-Melanoma Skin CA Abatacept: 15 (0.8%) Placebo: 6 (0.5%) Solid Organ CA Abatacept: 13 (0.7%) Placebo: 5 (0.5%) Hematologic Abatacept: 2 (0.1%) Placebo: 0

59 Immunogenicity was low in the abatacept clinical trial program Overall incidence of anti-abatacept antibody responses was 4.8% (187/3,985) in patients treated for up to 8 years with abatacept In patients assessed for antibodies at least 42 days after discontinuation of abatacept, incidence of immunogenicity was 5.5% (103/1,888) 1 – There was no apparent correlation of antibody development to clinical response or adverse event based on this limited dataset of patients with antibodies 1 59

60 60 BIOLOGICS AND PREGNANCY Drug# cases Developmental toxicity - animals Fetal problems – HumansDrug Discontinuation? ETA51-Preterm, VACTERL Vert,anal, CVS, tracheobr fistula, renal, & Limb At missed period, (+) pregnancy test INF81-TOF, intestinal malrotationAt missed period, (+) pregnancy test ADA13-Preterm, limb reduction, Tracheobronchomalacia At missed period, (+) pregnancy test RIT10B cell depletion (2 nd /3 rd tri) Lymphopenia (1 st tri)12 mos pre-pregnancy ABAT0+/None (?)unknown10 wks pre-pregnancy Ostensen M, Forger F. Management of RA medications in pregnant patients. Nat Rev Rheumatol 2009;5:382-90. UptoDate 2009 *1 case each - CZP, ANA, 0 - GOL and ABA; no animal and human/fetal toxicity reported; drug discontinuation recommended for GOL, CZP, ANA

61 Conclusions Abatacept in RA: Is efficacious in achieving remission in early RA Is efficacious in short and long term treatment Has a high retention rate Is a safe and reliable drug

62 62 THANK YOU


Download ppt "Treat to Target, Role of Orencia in Achieving the target. Prof. Hassan El-Shahaly Professor of Rheumatology and Rehabilitation Suez Canal University ELAR."

Similar presentations


Ads by Google