immuno-therapeutics

Question 1

swollen synovium

Answer 1

Swollen synovium contains:
Fibroblasts
Macrophages – activated to produce pro-inflammatory products eg. TNFα, IL-1, IL-6
T cells
B cells

Question 2

drugs commonly prescribed in rheumatology

Answer 2

NSAIDs
Corticosteroids

DMARDs
Conventional
Biologics

Question 3

NSAIDS

Answer 3

Symptomatic relief: used to relieve pain and swelling
No evidence of effect on erosions/progression
No agent any better than another
Difficult to assess the studies
(poor study design, many concomitant agents given)
Inter-patient variability

Question 4

NSAIDS contradictions and side effects

Answer 4

Contraindications
Active bleeding
Acute kidney injury
Drug interactions ?DOACs

Side effects – GI and cardiovascular
Gastroprotection
NSAID switching
COX-2 inhibitors

Question 5

corticosteroids

Answer 5

Mechanism of Action:

↓Monocytes and macrophages
↓ T-Cells
↑ Neutrophils
↓ Vessel permeability (IL-1, PG’s)
↓ proliferation of endothelial cells

Cochrane review: very effective for symptomatic relief in RA for up to 6 months (then declines).

Inhibits radiological progression/joint erosion, but only in initial years.
Co-morbidities

Diabetes, Osteoporosis, Immunosuppression

Question 6

corticosteroid regimes

Answer 6

Option for:
Early disease management
Bridging treatment
Flare management

Oral - Prednisolone (reducing course)

Intramuscular – Triamcinolone (Kenalog) variation in response/duration of response

Intra-articular – targets joint
Limit steroid injections to 3-4/year

Question 7

DMARDS

Answer 7

Conventional

Biologic
Original/Biosimilar

Targeted Synthetic

• methotrexate, sulfasalazine, hydroxychloroquine, leflunomide

Question 8

DMARDS: Methotrexate

Answer 8

MoA: Dihydrofolate reductase inhibitor
‘Gold standard’ first line moderate-severe RA; poor evidence in PsA (but used); some evidence in AS with peripheral joint involvement.

Dosing: Start at 7.5mg to 15mg weekly (depends on other factors and local practice); increase to 20mg to 25mg weekly.

Approx 2-3 months for full effect (max effect at 9 months).

Move to SC administration if GI side-effects or needing to exploit greater bioavailability.
Folic acid co-administration.

Question 9

DMARDS; Methotrexate, side effects

Answer 9

Side effects: GI, liver, lung, haematological
Baseline CXR, routine bloods

Interactions: Trimethoprim

Pregnancy and breast feeding: contraindicated

Withhold in infection

Monitoring: as per BSR DMARD guidance

Question 10

DMARDS: Sulfasalazine

Answer 10

Sulfasalazine: Sulfapyridine and 5-ASA

Intact SSZ may act like MTX as a folate antagonist, also inhibits TNF binding to membrane bound receptors. Individual components may ↓PG synthesis

Usual benefits including radiological (RA and PsA, less so in AS).

Question 11

DMARDS: Sulfasalazine side effects

Answer 11

Dosing: Start at 500mg OD and increase by 500mg increments/week until 2-4g daily.
A meta-analysis shows similar affect to MTX but again dosing problem (RA).
GI side-effects.
Hypersensitivity and rashes.
Fever, hepatitis, pneumonitis, aplastic anaemia
Infection – No need to withhold

Question 12

biologic therapy

Answer 12

Route of administration

Cautions/Contraindications
Infection, heart failure, malignancy, tuberculosis, hepatitis

Screening

Blood monitoring
?frequency

Side effects

Vaccinations
No live vaccines

Question 13

JAK inhibitors

Answer 13

The new kids on the block – Tofacitinib, Baricitinib, Upadacitinib, Filgotinib

Thought to revolutionise biologics given oral agents

However, EMA and MHRA warning issued Jan ‘23 due to concerns over MACE, venous thromboembolism and cancer risk.