Transcript Rheumatology Update 2014 - Aberdeen's Robert Gordon

Modern Therapeutics in
Rheumatic Diseases
Alistair Duncan (Clinical Pharmacist)
Lynn Sinclair (Rheumatology Nurse)
The Robert Gordon University
Non Medical Prescribing Conference 2014
Developments in Therapeutics for....
• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ankylosing Spondylitis
Biologics have revolutionised treatment
and outlook for those with inflammatory
joint diseases
Rheumatoid Arthritis
• Emphasis is now on:
– Early diagnosis
– Early (and aggressive) treatment
• Methotrexate is the GOLD STANDARD
treatment
Goals of Treatment
•
•
•
•
•
Reduce pain and inflammation
Preserve function
Maintain employment
Remission / Cure
Reduce cardiovascular risk
Symptomatic Control
• Analgesia
– As per WHO analgesic ladder
• NSAIDs
– Take into account co-morbidities
– COX 1 vs COX 2 selectivity
– Cardiovascular and GI side effects
• Steroids – i.m. / i.a. / oral
Traditional DMARDs
Disease Modifying Anti-Rheumatic Drugs
•
•
•
•
•
•
•
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Penicillamine
Ciclosporin
Gold (injection)
• Azathioprine
• Cyclophosphamide
• Chlorambucil
• Prednisolone
A: Placebo !
D: Azathioprine
G: Penicillamine
B: Auranofin
E: Methotrexate
H: IM Gold
C: Antimalarial
F: Sulfasalazine
Methotrexate
•
•
•
•
First used in 1947 for childhood leukaemia
Probably the most effective DMARD
Convenient ONCE weekly dosing ???
Faster onset of action (6 weeks to 3
months)
– (compared to other DMARDs)
• Mode of action - unclear!!
• Remember – Folic acid
Side Effects
• Nausea, stomatitis
• Haematological toxicity
• Hepatic toxicity
– LFTs, cirrhosis, hepatic fibrosis
• Pulmonary toxicity
– pneumonitis
• Teratogenic (ova and sperm)
Patient
specific
information
Responsibility of
the Consultant
Responsibility of
the GP +
monitoring
schedule
What to do if…?
Prescribing Information
General
Responsibilities
A Patient’s Story
Methotrexate Safety
• 2.5mg tablets and 10mg tablets now as
different shapes
• NHSG policy is to always prescribe 2.5mg
tablets
• Ensure patient understands dose in terms
of mg and number of tablets
• Avoid use of “as directed”
• Remove prescriptions from repeat piles
• Ensure regular monitoring
Methotrexate Prescribing Points
•
•
•
•
•
•
•
Ensure folic acid is prescribed
Avoid Trimethoprim (+ Co-trimoxazole)
Refer unexplained breathlessness/cough
Caution alcohol intake
Ensure adequate contraception
Avoid live vaccines
Follow shared care protocol
How to measure Rheumatoid
Arthritis?
28 Joint Count
DAS (28) Score
• Swollen and Tender Joint Count
• ESR
• Global health assessment by patient
DAS28 =
0.56 x sqrt(tender28) + 0.28 x
sqrt(swollen28) + 0.70 x ln(ESR) +
0.014 x GH
DAS in Practice
• “An objective method for measuring
disease activity”
• >5.1 = Active disease
• <3.2 = low disease activity
• <2.6 = Remission
Health Assessment
Questionnaire
• Dress yourself including tying shoe laces
and doing buttons
• Shampoo your hair
• Stand up from an armless straight chair
• Get in and out of bed
• Cut your meat
• Lift a full cup or glass to your mouth
• Walk outdoors on flat ground
Aids or devices that you may use
•
•
•
•
Cane
Crutches
Walking frame
Built up chair
Effect of a treatment strategy of tight control for
rheumatoid arthritis (the TICORA study): a singleblind randomised controlled trial
Catriona Grigor, MBChB, Hilary Capell, MD, Anne Stirling, RGN, Alex D McMahon,
PhD, Peter Lock, MSc, Ramsay Vallance, FRCR, Wilma Kincaid and Duncan Porter,
MBChB
The Lancet
Volume 364, Issue 9430, Pages 263-269 (July 2004)
DOI: 10.1016/S0140-6736(04)16676-2
Copyright © 2004 Elsevier Ltd Terms and Conditions
TICORA
• Tight Control for Rheumatoid Arthritis
• Intensive out-patient management of RA
vs Routine Care
• “Treat to target”
• If DAS > 2.4 , = step up in treatment
• Joints injected at monthly visits if
necessary.
Figure 3
Source: The Lancet 2004; 364:263-269 (DOI:10.1016/S0140-6736(04)16676-2)
Terms and Conditions
Treat to Target
Traditional DMARDs
Disease Modifying Anti-Rheumatic Drugs
•
•
•
•
•
•
•
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
Penicillamine
Ciclosporin
Gold (injection)
• Azathioprine
• Cyclophosphamide
• Chlorambucil
• Prednisolone
Biologics**
• Target pro-inflammatory cytokines
– Tumour necrosis factor (TNF) alpha
– Interleukin 6
– Interleukin 1
– Interleukin 12/23 (Ustekinumab for Psoriatic
arthritis)
• Other immune pathways
– B Cells
– T Cells
**All co-prescribed with MTX where possible
Eligibility for Biologics (SMC)
• Active disease (DAS > 5.1)
– On 2 occasions, 1 month apart
• Adequate therapeutic trial of at least 2
DMARDs (inc methotrexate)
Treat to Target - Next Steps
The nurses role in assessing
patients prior to commencing
Anti-TNF therapy
Medical Requirements
• Bloods checked for Hepatitis B + C core
Antibodies
• Recent chest x-ray
• No history of TB or MS
• No history of cancer
• Patient is not awaiting any
surgical/medical/dental procedures
• Consultant referral letter
• Ensure patient does not require to be TB
screened
• Varicella
• Does patient meet the DAS requirement to
commence Biologic (>5.1)
• What medication is the patient currently
using for arthritis?
Patient safe to
commence Anti-TNF
• When all investigations are completed and
the patient is safe to proceed with the
nurses assessment they will attend the
department to have a repeat disease
activity assessment (DAS)
• If patient has had recent steroids this may
reflect on the actual score
• The nurses role is then to assess the
patients joints for any tenderness or
swelling.
• ESR is obtained and recorded.
• Health assessment questionnaire filled in
by patient and results recorded.
• Pain score, early morning stiffness and
patients global assessed.
• All scores are entered into a DAS
calculator
Patient meets the criteria to
commence treatment.
• Education provided on the chosen drug
• Injection demonstrated to patient
– opportunity to familiarise themselves with the injection
device by using demonstration syringes
• Patient registered with Homecare company
– Injections delivered to patients home
– Homecare nurse to supervise patient doing first
injection.
• Nurse review at 3 months - DAS recorded.
• Nurses review again after 3 months, then 6
monthly thereafter.
Patient X Etanercept
• Patient currently has rheumatoid arthritis
and medical staff would like him assessed
for possibility of commencing anti tnf
therapy
• DAS prior to any treatment 7.64
• DAS 3 months after commencing
treatment 4.02
• DAS 6 months after commencing
treatment 2.16
Anti –TNF alpha
•
•
•
•
•
Certolizumab – fortnightly s/c inj.
Etanercept – weekly s/c inj.
Adalimumab – fornightly s/c inj.
Infliximab – 8 weekly iv infusion
Golimumab – monthly s/c inj.
• Typically (£9 - 10k per patient per year)
• S/C treatments via Homecare Company
TNFα and it’s Receptor
Recombinant TNFα Soluble Receptor
Monoclonal antibody against TNFα
Adverse Effects of
TNF Inhibitors
• Serious Infections
– TB
– Skin and soft tissue
– Blood borne viruses
• Malignancy
– ? Lymphoma
– ? Solid Tumors
– Conflicting data
• Injection site
reactions
• Infusion reactions
• Increased risk of
cardiac failure
• Demeyelination
When to with-hold biologics?
• Should be discontinued in the presence of
serious infections, but can be
recommenced once the infection has
resolved clinically.
• Stop biologic 3 to 5 half lives before major
surgery. Should not be restarted after
surgery until there is good wound healing
and no evidence of infection.
B Cell Depletion
• Rituximab
– 2 x fixed 1g doses 14 days apart
– IV infusion
– Dose repeated, but not at a fixed interval
Interleukin 6 Inhibitor
• Tocilizumab
• 4 weekly iv infusion
• Now available as weekly s/c injection
T Cell Co-Stimulation Modulator
• Abatcept
– 4 weekly iv infusion
– Now available as weekly s/c injection
Remember
• Always consider that a patient with
RA / AS / PSa may be on a drug
supplied via homecare
• Ensure recommended monitoring is
carried out.
• Caution in patients going for major
surgery, or with concurrent infection.
Info Resources
• British Society for Rheumatology (BSR)
• http://www.rheumatology.org.uk
• European League against Rheumatism
(EULAR)
• http://www.eular.org/
• Arthritis Research
• http://www.arthritisresearchuk.org/
• SIGN 123: Management of Early RA
• http://www.sign.ac.uk