biosimilar adalimumab symposium - dr sanjiv kapoor
TRANSCRIPT
SWITCHABILITY FROM OTHER BIOLOGICS TO ADALIMUMAB
DR . SANJIV KAPOORMD ( Medicine ), DM ( Clinical Immunology) SGPGI
LucknowConsultant Rheumatologist, Sanjivni Rheumatology Centre
and ISIC Superspeciality Hospital,
Vasant Kunj, New Delhi ISIC Hospital – 2000-
INTRODUCTION Agents that target tumor necrosis factor (TNF) are highly effective in treating patients with active rheumatic disorders, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA)
However, patients may not respond optimally to or may be intolerant of treatment with a given TNFi
A question faced by rheumatologists is whether switching to another TNFi is likely to result in an improved therapeutic response
SWITCHING EXPERIENC
E
In two open-label clinical studies, the effectiveness and safety of adalimumab in treating patients with active AS or PsA who had a history of therapy with IFX or ETN or both: Review of Safety and Effectiveness with
Adalimumab in Patients with Active Ankylosing SpOnDYlitis (RHAPSODY)1 and
SafeTy and Efficacy of Adalimumab in Patients with Active Psoriatic Arthritis (PsA): An Open- Label, Multinational Study to Evaluate the Response to Every-Other-Week Adalimumab When Added to Insufficient Standard Therapy including Patients Who Failed Prior Treatment With Other TNF-Inhibitors (STEREO)2
Analyses presented here includes patients who have shown inadequate response to IFX, ETN, or both
1. Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M, Carcereri-De-Prati R, Kupper H, Kary S: Effectiveness, safety, andpredictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol 2009, 36:801-808.2. Van den Bosch F, Manger B, Goupille P, McHugh N, Rødevand E, Holck P, van Vollenhoven RF, Leirisalo-Repo M, FitzGerald O, Kron M, Frank M, Kary S, Kupper H: Effectiveness of adalimumab in treating patients with active psoriatic arthritis (PsA) and predictors of good clinical responsesfor arthritis, skin, and nail lesions. Ann Rheum Dis 2010, 69:394-399.
METHODOLOGY
Criteria for Diagnosing SPA and Treatment with BIOLOGICS Adults at least 18 years of age with SPA according
to ASAS axial SpA criteria or ASAS peripheral SpA criteria ( 2011 )
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 and failure of ≥ 2 nonsteroidal antiinflammatory drugs (NSAIDs)
Prior treatment with ETN discontinued ≥ 3 weeks and IFX was discontinued ≥ 2 months before the first Adalimumab injection
Ref: Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A: A new approach to defining disease status in ankylosing spondylitis: the BathAnkylosing Spondylitis Disease Activity Index. J Rheumatol 1994, 21:2286-2291.
Treatment
strategy in
patients of AS
Aim: To keep BASDAI below 50% of the baseline
N= 15 patients on other TNF I switch to ADA Duration of study - 1 yrDrug : Infliximab was given 5mg/kg body wtInfliximab Inadequate response: Less than 50% decline in previous BASDAI1Switch Drug: Exemptia (Adalimumab): 40mg s.c. every other week ( TAPERING )
1. Van den Bosch F, Manger B, Goupille P, McHugh N, Rødevand E, Holck P, van Vollenhoven RF, Leirisalo-Repo M, FitzGerald O, Kron M, Frank M, Kary S, Kupper H: Effectiveness of adalimumab in treating patients with active psoriatic arthritis (PsA) and predictors of good clinical responsesfor arthritis, skin, and nail lesions. Ann Rheum Dis 2010, 69:394-399.
SWITCH strategies in AS
ASAS consensus recommend that disease activity levels should be followed using BASDAI
Active disease for >4 weeks BASDAI >4 (0–10)
RESPONDERS:Aim of the treatment to maintain BASDAI less than 50% of baseline
Ref: Ther Adv Musculoskel Dis (2010) 2(1) 3743 DOI: 10.1177/ 1759720X09359728 ! The Author(s), 2010. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.
Total Experience with Exemptia (Adalimumab)
AS; 41; 80%
RA; 4; 8%PsA; 6; 12%
Patients on Exemptia
Total no. of patients 51
SWITCHABILITY EXEPERIENCE
15 patients switch to Exemptia
from other TNF alpha inhibitors
13 patients were taking Infliximab 1 patient was started on Infliximab,
shifted to Etanercept than Adalimumab
1 patient on Etanercept
Ref: Spadaro A, Punzi L, Marchesoni A, Lubrano E, Mathieu A, Cantini F, Olivieri I, Salvarani C, Scarpa R, Scrivo R, Ramonda R, Porru G, D'Angelo S, Catanoso M, Atteno M, Valesini G. Switching from infliximab or etanercept to adalimumab in resistant or intolerant patients with spondyloarthritis: a 4-year study. Rheumatology (Oxford). 2010 Jun;49(6):1107-11
13
1, 1
Biologic Agent Switch
InfliximabEtanercept and then IFXEtanercept
Indication wise patients switched to Exemptia
PsA; 2; 13%
AS (Peripheral); 2; 13%
Juvenile -->AS; 2; 13%
AS with Uveitis & psori-asis; 1; 7%
AS with Uveitis; 3;
20%
AS(Axial+Peripheral); 5;
33%
No Of Patients
BASELINE VALUES OF PATIENTS BEFORE
STARTING EXEMPTIA
Characters ValueAge(in years) 40.5±9.26Male/Female 13/2Disease duration average 11 yearsHLA – B27 Positive 80% (12/15)Extra Articular Manifestation Enthesitis Uveitis Psoriasis
7/15 (47%)4/15 (26%)3/15 (20%)
BASDAI Mean 4.2ESR mean (mm/hr) 54CRP mean (mg/l) 50.4Hb mean 12.6Concomitant DMARD’s Steroids ( Intraarticular ) NSAID’s
13/15 (86.6%)4/15 (26.6%)6/15 (40%)
Infliximab mean duration 4.9 years
Reasons for Switch to Adalimumab Percentage
Secondary inefficiency 66.6% (10/15)
Uveitis flares inspite of IFX 20% (3/15)
Psoriasis not improved 13.3% (2/15)
Ref: Spadaro A, Punzi L, Marchesoni A, Lubrano E, Mathieu A, Cantini F, Olivieri I, Salvarani C, Scarpa R, Scrivo R, Ramonda R, Porru G, D'Angelo S, Catanoso M, Atteno M, Valesini G. Switching from infliximab or etanercept to adalimumab in resistant or intolerant patients with spondyloarthritis: a 4-year study. Rheumatology (Oxford). 2010 Jun;49(6):1107-11
TYPICAL EXEPERIENCE WITH EXEMPTIA
PATIENT JOURNEY –KEY ASSESSMENT PARAMETERSPRE & POST INFLIXIMAB
Patient Journey: BASDAI mean score – With Infliximab (Pre-Switch)
• IF-IR: Insufficient response defined as less than 50% improvement in BASDAI post infusion of IFX
IFXIFX
IFX
IFX-IR
Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 50.00.51.01.52.02.53.03.54.04.55.0
4.5
1.92.2
2.6 2.4
3.6
IFX
IFX- IR
Patient Journey: BASDAI mean score – with Exemptia (Post Switch)
Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 50
0.51
1.52
2.53
3.54 3.6
1.9 1.7 1.7
0.50.9
BASDAI
• BASDAI score reduced significantly in patients of EXEMPTIA, who had insufficient response to IFX
Exemptia
Patient Journey: VAS (Pain) mean score With Infliximab (Pre-Switch)
Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 50.0
10.020.030.040.050.060.070.0
58.8
32.3 27.8
45.039.1
50.4
VAS(Pain)IFX- IR
• IFX-IR: Patients with Inadequate response to IFX had increased Pain reported in follow up visits
IFX
Patient Journey: VAS (Pain) mean score With Exemptia (Post Switch)
Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 50.0
10.020.030.040.050.060.0
50.4
26.521.8
13.0 12.5 10.0
VAS (pain)Exemptia
• VAS score showed pain reduced significantly in patients of EXEMPTIA, who had insufficient response to IFX
Patient Journey: ESR mean score With Infliximab (Pre-Switch)
• IFX-IR: Patients with Inadequate response to IFX had increased Inflamatory markers(ESR) reported in follow up visits
Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 50.0
10.020.030.040.050.060.070.0
60.1
39.5 36.6 41.730.0
54.9
ESRIFX IFX- IR
Patient Journey: ESR mean score With Exemptia (Post Switch)
• Inflammatory marker (ESR) showed significant reduction in patients of EXEMPTIA, who had insufficient response to IFX
Baseline Visit 1 Visit 2 Visit 3 Visit 4 Visit 50.0
10.020.030.040.050.060.0
54.9
18.4 16.810.0 14.0 14.0
ESRExemptia
CASE 5(PK): AS WITH
DEVELOPMENT OF
INADEQUATE RESPONSE
TO IFX
Male patient Age: AS Diagnosis: AS (Axial+Peripheral) with
Chest Enthesitis Co-morbid condition: HTN On Infliximab for for 5 months developed
flare while on therapy Switch to Adalimumab : Started on
Exemptia 40mg s.c. and responded with immediate improvement in overall condition
Since then Adalimumab dose duration was increased
CASE 5(PK)
Baselin
e
2 Mon
th
5 Mon
ths
6 mon
ths
9 mon
ths
25 m
onths
28 m
onths
34 m
onths
35 m
onths
37 m
onths
010203040506070
00.511.522.533.544.55
45
30
13
60
40
8 6
22
1015
30
100
2030
0 0 0
20
0
35
0 010
1625
20
35
11.5
0
4.5
1 0.8
2.21.8
1 0.8
2.4
1.230.9
VAS(Pain)VAS(Global)InflammationBASDAI
IFX-IR Switch to Exemptia
Adverse event
Outcome of SpA
patients switched to ADA
Outcome of patients with ADA
Reason forswitch
Still taking ADAat the end ofOctober2016, n (%)
Stopped forinefficacy,n (%)
Stopped foradverseevents, n (%)
Inefficacy 15(100%) 0 0Adverse Events
0 0 0
Conclusion Few option available for treatment of Ankylosing
spondylitis and psoriatic arthritis Biological therapy is one of them, but effectiveness
of the treatment decreases with time Adalimumab is one of the option if patient is not
responding to Infliximab or Etanercept Patients responding very well to Adalimumab with
minimal side effects
ATYPICAL EXPERIENCE WITH EXEMPTIA
Persisting ACHILLES
TENDONITIS
Two Patients Diagnosis: AS with Enthesitis Co-morbid condition: On Remicade Started on Exemptia
40mg s.c. after persistanse of Heel enthesitis
Three doses
CASE 2(RTJ):
AS WITH HIP INVOLVEMEN
T
Male patient Age: 38 Diagnosis: AS Co-morbid condition: NIL On IFX for 5 yrs Left hip replaced two month back
Started on Exemptia 40mg s.c. after right Hip Involvement
CASE 4(CR):
AS WITH Uveitis Flare
Male patient Age: 31 years Diagnosis: AS (Peripheral) with Uveitis
flares in spite of Infliximab Disease duration: 15 years HLA B27: Negative Took remicade Started on Exemptia 40mg s.c. after
inadequate response in healing of of Uveitis
CASE 4(KL) AS with Uveitis Flare
Baseline 1 Month 2 Months 3 months0
1020304050607080
0
2
4
6
8
10
1270
53
30
3
6557.5 55
35
0
10
0 0
6.9
4.5
2.9
0.9
VAS(Pain)InflammationVAS(Global)BASDAI
IFX Uveitis Flare- Switch to Exemp-
tia
ADALIMUMAB TAPERING STRATEGY
DISCONTINUATION Definition of Remission or LDA
BASDAI <2 , 4 no peripheral symptoms and normal CRP Time of remission or LDA – 3 – 6
months Dose reduction was most frequently
done by increasing the interval between drug administration rather than decreasing the dose of the injection/infusion
75 – 80 % remain in remission
Definition of Remission or LDA ASAS 40 response ,
ASAS20 ,ASAS pr and remission on MRI , > 20% / 30% improvement in BASDAI
Outcome Flare definition BASDAI >4 and physician’s assessment of
disease activity > 4 or an increase > in BASDAI >2
79 % flair within 16 weeks ( 6 – 24 )
Tapering
THANK YOU