Rheumatoid arthritis - tofacitinib citrate

869 Pages·2017·14.94 MB·English

by  Jeremy Powell

Single Technology Appraisal

Tofacitinib for treating moderate to severe
active rheumatoid arthritis after the failure
of disease-modifying anti-rheumatic drugs
[ID526]

Committee Papers

© National Institute for Health and Care Excellence 2017. All rights reserved. See Notice of Rights. The content
in this publication is owned by multiple parties and may not be re-used without the permission of the relevant
copyright owner.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE

SINGLE TECHNOLOGY APPRAISAL

Tofacitinib for treating moderate to severe active rheumatoid arthritis after the
failure of disease-modifying anti-rheumatic drugs [ID526]

Contents:

1. Pre-Meeting Briefing

2. Company submission from Pfizer
 Submission
 Appendix - error and correction
 Addendum - revised PAS analyses

3. Clarification letters
 NICE request to the company for clarification on their submission
 Company clarification queries
 Company response to NICE’s request for clarification

4. Patient group, professional group and NHS organisation submission
from:
 National Rheumatoid Arthritis Society
 British Society for Rheumatology
 UK Clinical Pharmacy Association

5. Expert statements from:
 Dr Rajan Madhok, clinical expert, nominated by British Society for
Rheumatology
 Dr James Galloway, clinical expert, nominated by Pfizer Ltd
 Jennie Jones, patient expert, nominated by National Rheumatoid
Arthritis Society

6. Evidence Review Group report prepared by School of Health and Related
Research (ScHARR)
 ERG report
 ERG Erratum
 ERG Addendum

7. Evidence Review Group report – factual accuracy check

Any information supplied to NICE which has been marked as confidential, has been
redacted. All personal information has also been redacted.
© National Institute for Health and Care Excellence 2017. All rights reserved. See Notice of Rights. The content
in this publication is owned by multiple parties and may not be re-used without the permission of the relevant
copyright owner.
Pre-meeting briefing
Rheumatoid arthritis - tofacitinib citrate
This slide set is the pre-meeting briefing for this appraisal. It has been
prepared by the technical team with input from the committee lead team
and the committee chair. It is sent to the appraisal committee before the
committee meeting as part of the committee papers. It summarises:
• the key evidence and views submitted by the company, the consultees
and their nominated clinical experts and patient experts and
• the Evidence Review Group (ERG) report
It highlights key issues for discussion at the first appraisal committee
meeting and should be read with the full supporting documents for this
appraisal
Please note that this document includes information from the ERG before
the company has checked the ERG report for factual inaccuracies
The lead team may use, or amend, some of these slides for their
presentation at the Committee meeting
1
COMMON ABBREVIATIONS (shaded rows contain
comparator technologies)
ABA or
Abatacept ESR Erythrocyte sedimentation rate
ABT
ACR American College of Rheumatology ETN Etanercept
ACR EULAR European League Against Rheumatism
20/50/70% improvement in the ACR score
20/50/70
FACIT-F Functional Assessment of Chronic Illness Therapy-Fatigue
ADA Adalimumab
GOL Golimumab
AE Adverse event
HAQ-DI Health Assessment Questionnaire–Disability Index
AIC Akaikeinformation criterion
HR Hazard ratio
bDMARD Biologic disease-modifying anti-rheumatic drug
HRQoL Health-related quality of life
BNF British National Formulary
ICER Incremental cost-effectiveness ratio
BSR British Society for Rheumatology
INF or IFX Infliximab
BSRBR British Society for Rheumatology Biologics Register
IR Insufficient response
cDMARD Conventional DMARD
JAK Janus Kinase inhibitor
CG Clinical guideline
MTX Methotrexate
CHMP Committee for Medicinal Products for Human Use
NMA Network Meta-analysis
CI Confidence interval
QALY(s) Quality adjusted life year(s)
CZP Certolizumabpegol
SSZ or SFZ Sulfasalazine
DAS Disease activity score
TNFi Tumour necrosis factor inhibitor
EAM Extra-articular manifestation
TOC or TCZ Tocilizumab
EQ-5D EuroQol five-dimension questionnaire
TOF Tofacitinib
ERG Evidence Review Group
2
Key issues: Clinical effectiveness
• Is tofacitinib comparable to the bDMARDs in clinical effectiveness in
moderate and severe rheumatoid arthritis?
– Is the network meta-analysis a reliable estimate of the relative effect?
• Is tofacitinib effective as a monotherapy?
• Is the EULAR response derived from DAS 28 acceptable ?
• For the EULAR response outcome, does the true treatment effect lie
between estimates 1 and 2, but closer to estimate 1 than 2?
• Have the crossover issues been addressed appropriately?
• Is the safety profile of tofacitinib acceptable?
3
Key issues: Cost effectiveness
• Is tofacitinib comparable to the bDMARDs in both clinical effectiveness
and cost effectiveness?
• Has the case for tofacitinib monotherapy been proven?
• Do the ERG’s sequences better reflect the clinical practice than the ones
developed by the AG for TA375 (and accepted in BARI appraisal)?
• Are the deterministic results (and not probabilistic) appropriate for
decision making?
4
Rheumatoid arthritis
• An inflammatory autoimmune disease that typically affects the synovial tissue of
the small joints of the hands and feet but can affect any synovial joint, causing
swelling, stiffness, pain and progressive joint destruction.
– Systemic disease that can affect the whole body, including the lungs, heart
and eyes.
– A chronic relapsing condition which has a pattern of flare-ups followed by
periods of lower disease activity; however, for some people, the disease is
constantly progressive.
• Disease severity measured using the composite disease activity score (DAS28),
includes assessment of 28 joints for swelling/tenderness, the patient’s
assessment of health and erythrocyte sedimentation rate or C-reactive protein
– DAS28 <3.2 indicates low disease activity, DAS28 ≥3.2 and ≤5.1 indicates
moderate activity, and DAS28 >5.1 indicates high activity
• Associated with increased mortality and increasing disability, which has a severe
impact on quality of life.
• No cure, treatment aims to improve quality of life and prevent or reduce joint
damage
5
Relevant NICE technology appraisals
TA Treatment Population
Adults whose disease has responded inadequately to, or who cannot tolerate,
CTZ + MTX other DMARDs including at least 1 TNF inhibitor, only if:
6
51 • disease activity is severe and RTX is contraindicated or not tolerated
1
0
4
2
As above but only if:
CTZ monotherapy
• RTX therapy cannot be given because MTX is contraindicated or not tolerated
ADA, ETN, IFX, Disease is severe (disease activity score [DAS28] >5.1) and has not responded to
CTZ, GOL, TCZ, intensive therapy with a combination of cDMARDs
6
51 ABA (all + MTX)
7
0
3
2
ADA, ETN, CTZ, As above but for people who cannot have MTX because of contraindications or
TCZ monotherapy intolerance
Disease has responded inadequately to DMARDs and a TNF inhibitor and the
person cannot have RTX because it is contraindicated or not tolerated, and TCZ is
72 used as described for TNF inhibitor treatments in TA195, specifically the
41 TCZ + MTX
20 recommendations on disease activity or
2
the disease has responded inadequately to 1 or more TNF inhibitor treatments
and to RTX
51 Adults whose RA has responded inadequately to other DMARDs, including a TNF
21 GOL + MTX
20 inhibitor, if it is used as described for other TNF inhibitor treatments in TA195
2
Adults with severe active RA with an inadequate response to, or are intolerant of,
RTX + MTX
other DMARDs, including at least 1 TNF inhibitor.
50 ADA, ETN, IFX, As for RTX + MTX but for people who cannot have RTX because of
1
9
10 ABA (all + MTX) contraindications or intolerance
2
ADA, ETN As for RTX + MTX but for people who cannot have RTX because they have a
monotherapy contraindication to, or intolerance of MTX 6
Details of the technology
Technology Tofacitinib (Xeljanz, Pfizer)
Marketing Treatment of moderate to severe active RA in adult patients
authorisation • who have responded inadequately to, or
• who are intolerant to one or more DMARDs
− used as monotherapy or in combination with MTX
Mechanism Reversible janus kinase (JAK) inhibitor. Tofacitinib prevents full
of action activation of lymphocytes interrupting the inflammatory process
Administrati Oral, 5 mg twice daily. Treatment is continuous (no stopping rule), but
on dose reduction to 5 mg once daily may be considered for people
severe renal impairment (creatinine clearance <30mL/min) or
moderate hepatic impairment
Acquisition • List price: 5 mg x 56 tab: £690.03 (6-month treatment: £4,500.60
cost per patient; subsequent annual cost: £9,001.19 per patient)
• Simple PAS scheme (discount to the list price)
• Patient funding scheme in place to provide tofacitinib free-of-
charge to the NHS during the period where reimbursement is not
yet available in England and Wales.
Additional Tofacitinib was added to the EMA’s list of medicines under additional
information monitoring in April 2017
7
Positons of tofacitinib in the treatment pathway
Conventional DMARDs
(monotherapy or combination therapy with MTX)
Moderate RA
(DAS28 3.2-5.1)
Severe RA
cDMARDs with (DAS28 >5.1)
1
best supportive care
MTX intolerant/
Continue only if moderate EULAR response at 6 months MTX tolerated
contraindicated
MTX in combination with:
bDMARD monotherapy:
RXT contraindicated ABA, ETA, CTZ, ADA,
ADA, CTZ, ETA, TCZ
2 IFX, GOL, TCZ
TA375 2
TA375
RTX intolerant/
contra-indicated bDMARD in combination RTX intolerant/
bDMARD monotherapy: with MTX: contra- RTX in combination
indicated
ADA, CTZ, ETA ABA, ETA, CTZ, ADA, with MTX
4 3
TA375 IFX, GOL, TCZ 4 TA195
TA195, TA225, TA247
TCZ in combination
with MTX
• Shaded boxes=Potential positions of TOFA in the pathway
TA247
• 1-4=Patient populations referred to in the company submission
• BARI is currently being appraised by NICE at the same positions as TOFA in the treatment
pathway (FAD available June 2017, guidance to be published August 2017) 8