Benlysta - Treatment Options For Sle

Front 1

What is SLE?

Back 1

Is an autoimmune, connective tissue disorder with a broad range of presentations that can involve skin, joints, kidney, CNS, cardio, serosal membrane and hem and immune system

Front 2

Goals for therapy for SLE

Back 2

1. Management sysmptons and inductionof remission
2. Maintenance of remission
3. Prevention of long term damage

Front 3

Definition of Mild SLE

Back 3

Clinically stable disease

Front 4

Derfinition of moderate to severe SLE

Back 4

disease with major organ involvement or extensive involvement of nonmajor organs, failed response to steroids, and inability to tolerate high maintenance doses of corticosteroids

Front 5

How is SLE managed?

Back 5

1. Nonmajor organ (non visceral) involvement:agents with low side effects
2. Major organ (visceral) involvement: agents that change the immune system and therefore have more side effects

Front 6

Describe SLEDAI

Back 6

Global scoring system that provides measure of activity. Based on clinicians judgement on 24 abnormalities in 9 organs systems in last 10 days

Front 7

Define SLE flare or improvement by SLEDAI score

Back 7

1. Flare: increase in SLEDAI equal or greater than 3
2. Improvement decrease in SLEDAI equal or greater than 4

Front 8

Describe BILAG

Back 8

System based on the evaluation of disease activity in individual organs (8 organ systems)

Front 9

Describe PGA

Back 9

System is not specific to SLE and it is a visual analog scale 10 cm scale range 0-3

Front 10

List lab tests that may change (not always) preceding a flare up

Back 10

anti-dsDNA
Competent C3, C4 and CH50

Front 11

List nonpharmacologic treatment options

Back 11

1. rest and exercise (what i need)
2. diet management
3. routine health maintenance and immunizations
4. Minimize sun exposure
5. Sunscreen
6. Dont smoke
7. Reduce stress i.e. assessments - :-)

Front 12

Short term pharmacologic treatments

Back 12

1. Steroid pulse therapy
2. Pulse cyclophosphamide

Front 13

Long term therapies

Back 13

1. oral corticosteroids alone or in combination with immunosuppressives
2. Antimalarials
3. Long term azathioprine, mycophenolate mofetil, and methotrexate (control disease w/out steroids)

Front 14

List agents for pharmacologic approach

Back 14

1. NSAIDs
2. Corticosteroids
3. Antimalarials
4. Immunosupressive/Cytotoxic
5. Biologics

Front 15

3 FDA approved treatment options (prior to Benlysta)

Back 15

1. Corticosteroids
2. hydroxychloroquine
3. aspirin (symptomatic treatment of pleuritis and arthritis associated with SLE)

Front 16

Most trials of corticosteroids have been conducted in what type of SLE?

Back 16

Severe Lupus Nephritis

Front 17

Describe MOA of corticosteroids

Back 17

They are immunosupressive agents with MOA unknown. They have broad anti-inflamatory effects on multiple components of cellular immunity but little effect on humural immunity

Front 18

General doses of prednisone

Back 18

<7.5mg/day low dose
7.5 to <40mg/day moderate
>40mg considered high dose

Front 19

What is the major concerned with corticosteroids (describe)

Back 19

Toxicity: it supressess the natural production of corticosteroids by adrenal glands. Once you DC, it takes a while for natural production to begin. Sudden stop of corticosteroids can lead to several problems including: nausea, fatigue, hypotension

Front 20

Describe tapering process with corticosteroids

Back 20

Starts after the first 4 to 6 weeks of therapy. 0.25 mg/kg every other day at 2-3 months acceptable

Front 21

Describe advantage of Pulse therapy over high dose steroids

Back 21

Quicker response, but significant AEs can be observed (infection, GI, arrythmias, seizures and sudden death)

Front 22

Antimalarial drug of choice?

Back 22

Plaquenil (hydroxychloroquine)
An alternative is chloroquine (Aralen)

Front 23

Plaquenil MOA?

Back 23

Uncertain. It is thought that antimalarials interfere with T-lymphocyte activation

Front 24

Plaquenil dose

Back 24

200-400 mg/day. Responses occur within 1-3 months. Maximal effect 3-6 months. You can taper after 1-2 years
(Aranel dose 250-500 mg/day)

Front 25

What are moitoring requirements for antimalarials?

Back 25

(possible retinopathy)ophthalmogic at baseline and every 3 month with Aralen and 6-12 months with Plaquenil

Front 26

NSAIDs are commonly prescribed for patients with ________ disease

Back 26

"mild"

Front 27

List possible AEs for NSAIDs

Back 27

GI irratation, peptic ulceration, decrease renal function, hepatoxicity

Front 28

Percent of patients that receive cytotoxic therapy during course of disease?

Back 28

33%

Front 29

List immunosupressive/cytotoxic agents

Back 29

1. methotrexate (various)
2. Azathioprine (Imuran)
3. Cyclophosphamide (Cytoxan)
4. Mycophenolate mofetil (MMF) (CellCept)

Front 30

Agents focused on lupus nephritis are

Back 30

Azathioprine
Cyclophosphamide- (MMF has been recently introduced in order to reduced serious AEs)

Front 31

What are the benefits of cytotoxics in combination with steroids

Back 31

Allows for physicians to lower steroid dose and improve efficacy vs. steroids alone

Front 32

MOA of methotrexate

Back 32

It is an antimetabolite and antifolate agent with antineoplastic and immunosuppresant activities

Front 33

Methotrexate dose

Back 33

7.5 to15 mg./week in one to three doses with milk/water or food

Front 34

List common AEs for methotrexate

Back 34

GI, stomatitis, cytopenias. Methotrexate lung is a hypersensitivity reaction that can occur during first year

Front 35

Describe Azathioprine

Back 35

It is a purine analog with immunosuppressive activity. Primary use in induction therapy in mild cases. Long term use my decrease renal flare ups

Front 36

Dose of Azathioprine

Back 36

1 mg/kg/d with the usual maintenance dose being 2 to 3 mg/kg/d in one to three doses taken with food

Front 37

List common AEs for Azathioprine

Back 37

myleosuppression, opportunistic infections

Front 38

MOA of Cyclophosphamide

Back 38

Synthetic alkylating agent with antineoplastic and immunosuppressive activity.

Front 39

Describe general results of controlled clinical trials with Cyclophosphamide in SLE

Back 39

Improves long term outcomes in lupus nephritis. In combination with corticosteroids it decreases development of renal failure and transplantation. OS has not increased.

Front 40

List common AEs for Cyclophosphamide

Back 40

immunosuppression, opportunistic infections, bladder commplications, N&V, alopecia

Front 41

MOA of MMF (CellCept)

Back 41

Supresses T and B lymphocyte proliferation resulting in suppression of antibody synthesis

Front 42

Patient type for MMF

Back 42

MMF plus corticosteroids is a reasonable option in patients with mild to moderate nephritis and good renal function, patients with the severe form of lupus nephritis should receive cyclo + steroids

Front 43

MOA for Rituxan - Biologics

Back 43

chimeric monoclonal antibody. It is directed against CD20 on B cells. It depletes these cells via complement-mediated and antibody dependent cell mediated toxicity, induction of B cell apoptosis and inhibition of cell growth

Front 44

What are the 2 controlled studies NOT supporting the use of Rituxan?

Back 44

LUNAR and EXPLORER

Front 45

List common AEs for Rituxan

Back 45

Infusion reactions, cytopenias, tumor lysis syndrome, PML, infections,

Front 46

Give a brief description of ACR guidelines for treatment of SLE

Back 46

1. Prepared to improve quality of care for SLE patients
2. Based on evidence-based information for dx and mangement of disease
3. If evidence unavailable - guidelines based on SLE specialists

Front 47

Are there globally accepted guidelines for the treatment of SLE?

Back 47

No

Front 48

Describe ACR guidelines for mild SLE

Back 48

1. Patient education
2. Analgesic - PRN
3. NSAIDs - PRN
4. Topical glucocorticoid - rash
5. Sunscreen
6. Rest when flares appear
7. Antimalarials
8. Low-dose glucocorticoid therapy (specialist)

Front 49

Treatment guidelines for severe SLE

Back 49

Corticosteroids
Immunosuppressives/Cytotoxics

Front 50

Guidelines for severe SLE with no renal involvement

Back 50

IV IG
Plasmapheresis
Cyclosporin A
Anticoagulation - for patients with thrombotic events

Front 51

Guidelines for SLE with end stage renal disease

Back 51

Dialysis/renal transplantation

Front 52

Describe EULAR treatment recommendations for SLE

Back 52

They are based on evidence and expert opinion.Comprised of 19 specialists and clinical epidimiologist

Front 53

What are the areas of recommendation for SLE treatment by EULAR?

Back 53

1.Treatment of nonmajor organ involvement SLE
2.Adjunct therapy
3.Severe, inflamatory neuropsychiatric lupus
4.Lupus nephritis