Disease Modifying Anti-Rheumatic Drugs (DMARDs)

Question 1

Which drugs ares considered traditional (non-biologic) DMARDs? (4)

Answer 1

Methotrexate
Hydroxychloroquine
Sulfasalazine
Leflunomide

Question 2

MOA: TNF-alpha blockers (3)

Answer 2

Etanercept
Adalimumab
Infliximab

Question 3

MOA: B-cell depleter (CD20 mAb) (1)

Answer 3

Rituximab

Question 4

MOA: T-cell activation inhibitor (1)

Answer 4

Abatacept

Question 5

MOA: IL-6 receptor mAb (1)

Answer 5

Tocilizumab

Question 6

MOA: JAK3 inhibitor (1)

Answer 6

Tofacitinib

Question 7

MOA: Recombinant IL-1 antagonist (1)

Answer 7

Anakinra

Question 8

What drugs are considered “first-choice” for RA?

What is the drug of choice for additional pain relief, if needed?

Answer 8

NSAIDs.

Acetaminophen.

Question 9

What is the major clinical application of glucocorticoids in RA treatment?

Answer 9

To relieve pain and inflammation while waiting for DMARD effects and for flares.

Question 10

What are the 2 MOAs of glucocorticoids in treatment of RA?

Answer 10

1. GR complexing with NF-kB and AP-1 transcription factors (immunosuppression).
2. Activation of lipocortin (PLA2 inhibitor) is activated.

Question 11

What is the benefit of adding F to prednisone?

Answer 11

It increases the potency and half-life.

Question 12

For what time period are glucocorticoids more effective than NSAIDs?

What daily dosage can be taken without significant adverse-effect?

Answer 12

< 1 mo.; they tend to be effective for < 6 mo.

< 5 mg/day, but does not reduce disease progression.

Question 13

What features suggests “mild RA”? (4)

Answer 13

< 5 inflamed joints.
NL or elevated ESR and CRP.
No extra-articular disease.
May lack poor prognostic features such as RF and anti-CCP.

Question 14

What features suggest “moderate RA”?

Answer 14

> 5 inflamed joints.
Elevated ESR and CRP.
+RF and anti-CCP.
Evidence of inflammation is seen on XR (joint space narrowing, peripheral erosions, etc.)

Question 15

What is the MOA of methotrexate (MTX)? (2)

Answer 15

Inhibition of dihydrofolate reductase.

Undergoes polyglutamination, which accumulates in cells over weeks and blocks thymidylate synthase and AICAR. AICAR accumulation leads to adenosine efflux which binds to cell receptors and exerts anti-inflammatory effects.
*blocks thymidine and purine syntheses.

Question 16

How soon will effects be seen with MTX use?

How often is it given?

Answer 16

3-6 wks. - faster acting than all other DMARDs.

Once per week, either orally or by injection.

Question 17

MTX should be taken with which supplement?

What are the adverse-effects? (4)

What can it cause in pregnancy?

Answer 17

Weekly folate supplementation.

Bone marrow suppression, hepatic fibrosis, GI ulceration and pneumonitis.

Fetal death and congenital abnormalities.

Question 18

What is the MOA of Hydroxychloroquine?

How long does it take to kick in?

Answer 18

Increases pH of lysosomal vesicles in APCs limits association of peptides with class II MHC.

3-6 mo.

Question 19

What DMARD is considered safe in pregnancy?

Answer 19

Hydroxychloroquine

Question 20

What is the major adverse-effect of Hydroxychloroquine?

Answer 20

Retinal damage; otherwise it is pretty safe.

Question 21

What drugs constitute “triple therapy” for RA treatment?

Answer 21

MTX, hydroxychloroquine and sulfsalazine.

Question 22

What side-effects are most common for Sulfsalazine?

Answer 22

GI-related side-effects.

Question 23

What is the MOA of Leflunomide?

Answer 23

Inhibition of dihydroorotate dehydrogenase to block the synthesis of rUMP –> inhibits T-cell proliferation.

Question 24

What are the most common side-effects of Leflunomide? (5)

Answer 24

Diarrhea
URI
Reversible alopecia
Rash
Liver/Gb dysfunction

Question 25

Biologic DMARDs can NEVER be used in combo with…

Answer 25

Other biologic DMARDs.

Question 26

As compared to non-biological DMARDs, biologics tend to have…

Answer 26

Faster onset of action and a higher rate of response.

They also tend to be more expensive and have a greater risk for side-effects.

Question 27

What side-effects are notable with TNF-alpha antagonist usage? (2)

Answer 27

Serious infection, like Tb, Hep. B, etc.

Severe allergic reactions.

Question 28

How often is Adalimumab (Humira) given?

How often is Infliximab given?

How often is Etanercept given?

Answer 28

SubQ every 2 wks.

IV infusion every 6 wks.

Once or twice weekly via subQ injection.

Question 29

What does “-cept” suggest?

Answer 29

Fusion of a receptor to the Fc part of human IgG1.

Question 30

What tends to predict a greater likelihood of responsiveness of a patient to Rituximab?

Answer 30

+RF and +anti-CCP.

Question 31

What is the major adverse-effect of Rituximab?

What are other, less likely, adverse-effects? (3)

How often is Rituximab given?

Answer 31

Infusion-related hypersensitivity reactions.

Stevens-Johnson syndrome, Hep. B reactivation and PML.

Via IV infusion every 6 mo.

Question 32

How does Abatacept inhibit T-cell activation?

Answer 32

It prevents CD28 from binding to its counter-receptor CD80/CD86.

It is generally well-tolerated, but the major side-effects are infectious.

Question 33

What is the effect of Tocilizumab’s inhibition of IL-6?

Answer 33

It limits hepatic acute phase response and activation of T-cells, B-cells, Mo and osteoclasts.
*IL-6 levels are abnormally high in AI diseases.

Question 34

What is the most common adverse-effect of Tocilizumab?

There is a small risk for which others? (3)

Answer 34

URIs are most common.

There is a small risk of life-threatening infections, GI problems and neutropenia/thrombocytopenia.

Question 35

What is the effect of Tofacitinib’s inhibition of JAK3?

What is the drawback of its use?

Answer 35

It directly suppresses production of IL-17 and IFN and proliferation of CD4+ cells.

It is used orally and is outrageously expensive since its discovery.

Question 36

What are the adverse-effects of Tofacitinib? (2)

Answer 36

Serious and sometimes fatal infections due to opportunistic pathgens.
Increased malignancies.

Question 37

What are the adverse-effects of Anakinra? (2)

Answer 37

Serious infections.

Hypersensitivity reactions.