Psoriasis treatments

Question 1

What is the structure of Etanercept (Enbrel )?

Need to check from what age is it approved in children

Answer 1

Fusion protein consisting of the extracellular domain of two p75 TNF receptor fused with the Fc portion of human IgG1.
In the Bolognia text pg 2247 approved for children ages 4-17.

Question 2

What is the approved dosage for moderate to severe plaque type psoriasis ?

Children dosage ?

Answer 2

Subcutaneously 50mg twice weekly for the first 3 months, followed by 50 mg weekly.

For children: 0.8 mg/ kg ( maximum 50 mg ) weekly.

Question 3

What are cutaneous side effects of Tumor Necrosis factor inhibitors :

Answer 3

1) New onset psoriasis, especially palmoplantar pustulosis.
2) interstitial granulomatous dermatitis and other granulomatous eruptions.
3) cutaneous small vessel vasculitis
4) eczematous eruptions
5) Lichenoid dermatitis
6) Lupus-like syndrome associated malar rash or discoid lesions.
7) Other types of cutaneous lupus, e.g. SCLE, chilblain lupus.

Question 4

Infliximab ( Remicade ) is ..,

Answer 4

Chimeric human-mouse monoclonal IgG1 antibody that target human TNF.

Question 5

For Sarcoidosis , which TNF inhibitors is effectivevand which one is not ?

Answer 5

Effective :  Infliximab -Remicade
Not effective ( failed to improve systemic manifestations of sarcoudosis in randomized controlled trials) : Enbrel.

Question 6

What cutaneoys diseases were treated with Infliximab effectively ?

Answer 6

Pyoderma gangrenosum ( whether or not it is associated with IBD)

• Sarcoidosis
• Granulomatous cheilitis
• Behcet disease
• various vasculitidew
• PRP
• reactive arthritis
• subcorneal pustular dermatosis
• GVHD
• Sjogren syndrome
• multicentric reticulohistyocytosis
• Hidradenitis suppurativa

Question 7

Infliximab regimen for psoriasis is :

Answer 7

5 mg/ kg administered by slow IV infusion
At
0 , 2 weeks , 6 weeks

And then every 8 weeks.

However, doses ranging from 3-10 mg/kg have been utilized.
Frequency and dose can be adjusted when the response is inadequate.

Question 8

Loss of efficacy of Infliximab over time is related to :

Answer 8

Development of neutralizing anti-chimeric antibodies and has been associated with the presence of ANA.

The concurrent administration of low-dose weekly methotrexate may help to prevent the formation of anti-chimeric antibodies.

Question 9

How to reduce risk of Influximab infusion reactions ( which has been linked to presence of human antichemeric antibodies )

Answer 9

Slower infusion rate

Concomitant use of methotrexate , azathiopribe , or corticosteroids.

Question 10

Adalimumab is

Answer 10

Human recombinant IgG1 monoclonal antibodies with specificity for human TNF

Question 11

Adalimumab dosage for psoriasis :

Answer 11

Subcutaneous

Initial loading dose : 80 mg
Day 8 : 40 mg
Then 40 mg every other week.

Question 12

Adalimumab benefits for hidradenitis suppurativa

Answer 12

Approved for HS
40-60% of patients achieving a 50% reduction in the abscess/inflammatory nodule count with no increase in the draining fistula count.

Question 13

Adalimumab dosage for HS

Answer 13

Loading dose : 160 mg
Day 15 : 80 mg
Day 29 and on : 40 mg weekly

Question 14

Stelara is … works by…

Answer 14

Ustekinumab is a human IgG1 monoclonal antibody that targets IL-12 and IL-23.
It binds with high affinity and specificity to the p40 subunit that is shared by the heterodimeric IL-12 and IL-23 cytokines.

IL -12 has a critical role in the development of TH1 cells and NK cell activation.

IL-23 is necessary for the generation of Th17 cells.

Question 15

Guselkuman ( Tremfya) , Risankizumab ( Skyrizi) and tildrakizumab target…

Answer 15

The p19 subunit of IL-23.

Question 16

Stelara dosage

Answer 16

Subcutaneous injection

For <100 KG : 45 MG
FOR > 100 Kg : 90 MG

Weeks 0, 4 weeks and then every 12 weeks.

Question 17

Guselkumab ( Tremfya ) dosage

Answer 17

Subcutaaneous injection

100 mg

At 0, week 4, and then every 8 weeks.

Question 18

Ustekinumab side effects

Answer 18

Increases incidence of mucocutaneous candidiasis ( %5 of patients )
A potential risk of severe and disseminated infections with mycobacteria and Salmonella.

Cardiovascular : individual trials showed possible excess risk of major adverse cardiovascular events but meta analyses and 5 year followuo did not find an increased risk

Could ptentially increase the risk of malignancies.

Should be avoided in patients with serious active infections or malignancies.

Question 19

Name IL-17 inhibitors

Answer 19

Ixekizumab - Taltz - humanized IgG4 monoclonal antibody that binds and inhibits IL-17A, resulting in neutralization of IL17A homodimers and IL-17A/F heterodimers.

Secukinumab -Cosentyx - a human IgG1k monoclonal antibody that binds with high affinity and selectiveky to IL-17A

Brodalumab - Siliq - human IgG2k monoclinal antibody that selectively binds the IL-17 receptor A, inhibiting its interactions with IL17A/F and IL-17E.

Question 20

Contraindications for IL-17 inhibitors

Answer 20

Caution in patients with chronic /recurrent infections or inflammatory bowel disease

Crohn disease representing a CI for brodalumab.

Avoided or discontinued in patients with a serious active infection.

Question 21

Side effects 9f IL-17 inhibitors are :

Answer 21

Most common :
Nasopharyngitis
Upper respiratory tract infections
Injection site reaction

Others:
** Hypersensitivity reactions including anaphylaxis, angioedema, and urticaria.

** Mucocutaneous candidiasis ( mild to moderate) ,most often oral or vulvovaginal, develops in ~5% of patients. ( reflects the important role of IL-17 in defense againat Candida.

**Neutropenia: <1500 cells/mm3 occurs in 1-2% of patients ( similar ro Etanercept)

** New onset and excacerbation of Crohn disease and ulcerative colitis.

NOT observed : increased risk of advwrse cardiovascular events in clinical trials.

Question 22

Ixekizumab dosage regimen is

Answer 22

Loading dose of 160 mh
80 mg every 2 weeks for 12 weeks
80 mg every 4 weeks.

Question 23

Secukinumab -Cosentyx dosage

Answer 23

Subcutaneous injection of
300mg at weeks 0, 1, 2, 3, and 4 and thereafter it is given every 4 weeks.

A dose of 150 mg may be considered for patients weighing < 90 kg.

Question 24

Brodalumab indication and dosage

Answer 24

Mod to severe psoriasis in adults who have failed or become unresponsive to other systemuc therapies.

Subcutaneous 210 mg every 2 weeks.

It is contraindicated in Crohn disease and suicidal ideation as well as suicides occured during clinical trials.!!!!!