biosimilar adalimumab symposium - dr sanjiv kapoor

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