Treatment of RMDs

Question 1

Describe the initial treatment plan for RA with MILD disease activity at initial presentation: not pregnant or planning pregnancy

Answer 1

1st Line: conventional DMARD:
- hydroxychloroquine - it is better tolerated and has a more favourable risk profile than other DMARDs

Consider: Corticosteroid
- Prednisolone

Consider: non-steroidal anti-inflammatory drug (NSAID)
- ibuprofen

NB: hydroxychloroquine: should only be considered for initial therapy if mild

BMJBP

Question 2

Describe the initial treatment plan for RA with MODERATE-SEVERE disease activity at initial presentation not pregnant or planning pregnancy

Answer 2

1st line cDMARD:
- methotrexate (primary option) with folic acid supplementation
- sulfasalazine (secondary option)
- hydroxychloroquine (secondary option)
- leflunomide (secondary option)
- bridged with corticosteroid - prednisolone for 2/3 months until methotrexate starts working

2nd line: Combination treatment with multiple cDMARDs

3rd line: bDMARDs
- etanercept (primary option)
- infliximab
- adalimumab

4th line: Rituximab

Double check with lecture

Question 3

TOM TIP: The main biologics to remember are [3] (TNF inhibitors), and [1] (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).

Answer 3

TOM TIP: The main biologics to remember are adalimumab, infliximab and etanercept (TNF inhibitors), and rituximab (a monoclonal antibody that targets the CD20 proteins on the surface of B cells).

They cause immunosuppression, increasing the risk of infection, certain cancers (e.g., skin) and reactivation of latent TB.

Question 4

Describe the dosing regimen for methotrexate [1]

Answer 4

Methotrexate interferes with folate metabolism and suppresses the immune system. It is given once a week

Folic acid 5mg is taken once a week (on a different day to the methotrexate)

Question 5

Describe the MoA of Leflunomide [1]

Name 5 side effects [5]

Answer 5

Leflunomide is an immunosuppressant medication that interferes with the production of pyrimidine.

Side effects:
* Mouth ulcers and mucositis
* Increased blood pressure
* Liver toxicity
* Bone marrow suppression and leukopenia (low white blood cells)
* Teratogenic (harmful to pregnancy) and needs to be avoided before conception in both women and men
* Peripheral neuropathy

Question 6

TOM TIP: The unique side effects worth remembering are:
- Methotrexate [3]
- Leflunomide [2]
- Sulfasalazine [3]

Answer 6

TOM TIP: The unique side effects worth remembering are:

Methotrexate:
* Bone marrow suppression
* leukopenia
* highly teratogenic

Leflunomide:
- Hypertension
- peripheral neuropathy

Sulfasalazine:
- Orange urine
- male infertility (reduces sperm count)

Question 7

TOM TIP: The unique side effects worth remembering are:
- Hydroxychloroquine [3]
- Anti-TNF medications [2]
- Rituximab [2]

Answer 7

Hydroxychloroquine:
- Retinal toxicity
- blue-grey skin pigmentation
- hair bleaching

Anti-TNF medications:
- Reactivation of tuberculosis

Rituximab:
- Night sweats
- thrombocytopenia

Question 8

[2] are considered the safest DMARDs in pregnancy

Answer 8

Hydroxychloroquine and sulfasalazine are considered the safest DMARDs in pregnancy

Question 9

Which RA medication has a risk of reactivating TB? [1]

Answer 9

Etanercept and also
adalimumab, infliximab, golimumab and certolizumab

Question 10

Which RA medication has a risk of an infusion reaction? [1]

Answer 10

Rituximab

Question 11

How do you treat a flare of RA? [1]

Answer 11

flares of RA are often managed with corticosteroids - oral or intramuscular
- methylprednisolone

Question 12

What needs to be checked before starting DMARDs?

Answer 12

Hepatitis B and C status, purified protein derivative (PPD), FBC, and LFTs need to be checked before starting DMARDs.

Question 13

State 5 side effects of corticosteroids

Answer 13

Osteoporosis; weight gain; DM; HTN

Question 14

Methotrexate:
1. MoA?
2. Advantages [3]
3. Disadvantages [6]

Answer 14

MoA:
- Folic acid inhibitor (due to inhibition of dihydrofolate reductase) which stops cell proliferation; impacts rapidly dividing cells

Advantages:
- Inexpensive
- Oral or injection
- Well established safety profile

Disadvantages
- N&V
- Mouth sores
- Hair loss
- Liver toxicity
- Bone marrow suppresion
- Lung toxicity

Question 15

What do you screen for prior to starting methotrexate; SSZ and LEF tx? [3]

Answer 15

• FBC; UEs; LFTs
• Viral serology screen
• Baseline CXR - for MTX as can cause PF
• Baseline BP for LEF

Question 16

How do you manage / monitor ongoing methotrexate; SSZ and LEF prescription? [3]

Answer 16

FBC and LFTs are to be monitored every 2 weeks for the
first 6 weeks (induction phase) and with any increased
dose, and then monthly for 3 months.

Question 17

3-monthly monitoring for MTX, SSZ, and LEF includes..? [5]

Answer 17

3 monthly FBC; ALT; AST; ALP; Albumin; U&Es

Question 18

What important AE do you need to monitor for with hydroxychloroquine tx? [1]

Answer 18

Retinal toxicity - requires regular eye exams

Also: gastrointestinal upset, skin rash

Question 19

Describe the MoA [1] and AEs [3] of MMF

Answer 19

MoA:
- Inhibits enzyme used for de novo purine synthesis - effects T & B cells

AEs:
- GI upset
- Infections
- Bone marrow suppression

Question 20

What should you offer women prior to cyclophosphamide treatment? [1]

Answer 20

Egg harvesting treatment as causes infertility

Question 21

Describe the MoA and side effects of cyclophosphamide

Answer 21

MoA:
- Alkylating agent - cross links DNA strands, leading to cell death

Effects:
- Bone marrow suppression
- Bladder inflammation - hamorrhagic cystitis
- Infertility
- N&V

Question 22

Describe some of the unwanted effects of blocking TNFa

Answer 22

TNFa is essential for granuloma formation, organisation and maintenance - risk of TB reactivation AND increased risk of infection

Autoimmune reactions:
- paradoxical psoriasis (new onset or worsening)
- drug induced lupus
- MS or optic neuritis

Allergic reactions
HF exacerbations
Blood abnormalities (anaemia; neutropenia)
Liver toxicity
Increased risk of malignancies

Question 23

What should you screen for prior to anti-TNF tx? [4]

Answer 23

FBC ++
Serology for HIV, HBV & HCV
CXR and TB Elispot
Exclude infections, pregnancy, malignancy, NYHA Class III/IV and EF < 50%

Question 24

antibodies to antibodies

Answer 24

Can produce antibodies agaisnt

Question 25

Name an anti-TNF that can be used in pregnancy [1]

Answer 25

Certolizumab

Question 26

Name an anti-TNF that might cause less chance of infection [1]

Answer 26

Etanercept

Question 27

Whats an overall JAK inhibitor MoA? [1]

Answer 27

JAKs are inside the cells (block the messages delivered by cytokines inside the cells)

There are different JAKs

Question 28

Name an advantage of JAK inhibitors tx [1]

Answer 28

Can be taken orally (c.f. biologics are often infusions)

Question 29

Name some side effects of JAK inhibitors [4]

Answer 29

Increased risk of serious infections - use in caution with > 65

Risk of MACE - caution with CVD

Malignancy - particularly increased risk of lymphoma and lunger cancer

Thrombotic events; GI side effects and anaemia

Question 30

Describe the treatment pathway for RA

Answer 30

Question 31

Which alternative drug should be used if pregnant or pregnancy planning? [1]

Answer 31

Sulfasalazine

Question 32

How often do you perform blood tests for methotrexate monitoring? [1]

Question 33

How do you assess response to methotrexate use? [1]

Answer 33

Assess using DAS28 = disease activity score of 28 joints