II - Inflammatory Skin Conditions

Systemic medications for Psoriasis?

Non-biologics

• Phosphodiesterase 4 (PDE-4) inhibitors

• Tyrosine Kinase (TYK2) inhibitors

Biologics

• Tumor Necrosis Factor (TNF) inhibitors

• IL 17 inhibitors

• IL 12/23 inhibitors

• IL 23 inhibitors

• IL 36 inhibitors

What are biologics?

Large complex molecules that are made from living sources

Complicated to purify, process,and manufacture

Can vary from batch to batch

Biosimilar products?

A biologic medication that is highly similar to and has no clinically meaningful differences from an existing FDA-approved biologic product

Not a “generic”

Goals and expectations for systemic psoriasis medications?

Symptom management/improvement → no cure

May take a long time to see full benefit of medications

Duration of therapy → indefinite

Examples of TNF inhibitors for psoriasis??

Adalimumab → Humira

Etanercept → Enbrel

Certolizumab → Cimzia

Infliximab → Remicade

TNF inhibitors MOA?

Inhibit tumor necrosis factor (TNF) → a cytokine involved inflammatory and immune responses

Humira dosing?

Adult

LD → Initial dosing on day 0 and 7

MD → every 2 weeks

How is Humira supplied?

Pen and Syringe

SUBQ

TNF INHIBITOR

Enbrel dosing?

Adult and PEDs

Ld→ two times weekly for 3 months

MD → weekly

How is Enbrel supplied?

Pen, syringe, vial, mini

SUBQ

TNF INHIBITOR

Cimzia dosing?

Adult

MD only → dose every 2 weeks

How is Cimzia supplied?

Syringe

SUBQ

TNF INHIBITOR

Remicade dosing?

Adult

LD → IV at 0, 2, 6 weeks

MD → IV every 8 weeks

How is Remicade supplied?

Vial for IV infusion

TNF INHIBITOR

TNF inhibitors in pregnancy?

May be continued during pregnancy → can stop at 27 weeks to reduce risk of immunosuppression in infant

• If therapy is continued past 27 weeks → do not give live vaccines to infant for 6 months

Use Cimzia → minimal transfer across placenta to fetus

Examples of interleukin (IL)-17 inhibitors for psoriasis?

Secukinumab → Cosentyx

Ixekizumab → Taltz

Bimekizumab → Bimzelx

Brodalumab →Siliq

MOA of IL-17 inhibitors?

mAB selectively binds with interleukin 17A → IL-17A cytokine and inhibits its interaction with the IL-17 receptor

Cosentyx dosing ?

Adult and PEDs

LD → once weekly for 5 weeks

MD → once every 4 weeks

6 and older

How is Cosentyx supplied ?

Pen and Syringe

SUBQ

IL-17 INHIBITOR

Taltz dosing ?

Adult and PEDs

LD → large initial dose, then small dose every 2 weeks for 6 weeks

MD → dose every 4 weeks

Ages 6 and older

How is Taltz supplied?

Pen and Syringe

SUBQ

IL-17 INHIBITOR

Bimzelx dosing?

Adult

LD → dose every 4 weeks for 16 weeks

MD → dose every 8 weeks

How is Bimzelx supplied?

Pen and Syringe

SUBQ

IL-17 INHIBITOR

Siliq dosing?

Adult

LD → dose at week 0, 1, and 2

MD → dose every 2 weeks

How is Siliq supplied?

Syringe only

SUBQ

IL-17 INHIBITOR

Example of IL-12/23 inhibitors for psoriasis?

Ustekinumab → Stelara

MOA of IL-12/23 inhibitor?

Inhibit interleukins 12 and 23 → cytokines involved in inflammatory and immune responses

Stelara dosing?

Adult and PEDs

LD → dose at 0 and 4 weeks

MD → dose every 12 weeks

Ages 6 and older

How is Stelara supplied?

Vial and Syringe

SUBQ / IV

IL-12/23 INHIBITOR

Examples of IL-23 inhibitors for psoriasis?

Guselkumab → Tremfya

Risankizumab → Skyrizi

Tildrakizumab → Ilumya

Icotrokinra → Icotyda

MOA for IL-23 inhibitors?

IgG1 mAB selectively binds to the p19 subunit of human IL-23 cytokine and inhibits its interaction with the IL-23 receptor

Tremfya dosing?

Adult and PEDs

LD → dose at weeks 0 and 4

MD → dose every 8 weeks

Ages 6 and older

How is Tremfya supplied?

Pen and Syringe

SUBQ
IL-23 INHIBITOR

Skyrizi dosing?

Adult

LD → dose at weeks 0 and 4

MD → dose every 12 weeks

How is Skyrizi supplied?

Pen and Syringe

SUBQ

IL-23 INHIBITOR

Ilumya dosing?

Adult

LD → dose at weeks 0 and 4

MD → dose every 12 weeks

How is Ilumya supplied?

Syringe only

SUBQ

IL-23 INHIBITOR

Icotyde dosing?

Adult and PEDs

LD → dose by mouth once daily

MD → dose by mouth once daily

Ages 12 and older

How is Icotyde supplied?

Tablets

ORAL

IL-23 INHIBITOR

Examples of IL-36 inhibitors?

Spesolimab-sbzo → Spevigo

MOA of IL-36 inhibitor?

mAB binds to IL-36 receptor and prevents activation of proinflammatory and profibrotic pathways

What is IL-36 inhibitor indicated for?

Only for generalized pustular psoriasis

Spevigo flare dosing?

Adults and PEDs

LD → dose IV once

MD → dose IV may be given one week later

Ages 12 and older

Spevigo maintenance dosing?

LD → dose SQ at week 0 then another dose SQ at week 2

MD → dose SQ every 4 weeks

How is Spesolimab / Spevigo supplied?

Vial and Syringe

SUBQ AND IV

IL-36 INHIBITOR

Examples of phosphodiesterase 4 (PDE-4) inhibitors for psoriasis?

Otezla

Topical - Zoryve

MOA of PDE-4 inhibitors?

Inhibits PDE4 specific for camp → results in increased intracellular cAMP levels and regulation of numerous inflammatory mediators

Otezla dosing?

Adult

LD → Dose titration over 6 days

MD → dose orally twice daily

How is Otezla supplied?

Starter pack → 10, 20, and 30mg tablets

Tablets

ORAL
PDE-4 INHIBITOR

Zoryve dosing?

Adult and PEDs

MD → Apply topically once daily

Ages 6 and older

How is Zoryve supplied?

Cream/Foam

TOPICAL
PDE-4 INHIBITOR

Monitoring for PDE-4 inhibitors?

DI → strong CYP450 inducers → rifampin, phenobarbital, carbamazepine, phenytoin

Monitor → Weight/GI, renal function, mood changes

Pregnancy with PDE-4 inhibitors?

Otezla → do not use if trying to get pregnant/currently are

No data on Zoryve

Lactation with PDE-4 inhibitors?

Otezla → transfer into breast milk

Unknown in Zoryve

Examples of Tyrosine Kinase 2 (TYK-2) inhibitors for psoriasis?

Sotyktu

MOA of Tyrosine kinase 2 (TYK-2) inhibitor?

Prevents downstream activation of signal transducers/activators of transcription (STATs) and subsequent cytokine pathways

Sotyktu dosing?

Adult

Dose once daily

How is Sotyktu supplied?

Tablets

ORAL
TYK-2 INHIBITOR

How are TYK-2 inhibitors stored and administered?

Stored → Room temp

Administration → with or without food, swallow tablets whole

Missed dose → take as soon as you remember, do NOT double up

What drugs are not immunosuppressing for psoriasis?

PDE-4 Inhibitors

• Otezla

• Zoryve

What drugs can be used for PEDs psoriasis?

Enbrel →TNF

Cosentyx → IL-17

Taltz → IL-17

Stelara → IL-12/23

Tremfya → IL-23

Icotyde → IL-23

Spevigo → IL-36

Zoryve → PDE4

What drugs are adults only for psoriasis?

Humira → TNF

Cimzia → TNF

Remicade → TNF

Bimzelx → IL-17

Siliq → IL-17

Skyrizi → IL-23

Ilumya → IL-23

Otezla → PDE-4

Sotyktu → TYK-2

What are the systemic medications used for atopic dermatitis?

Non-biologic

• JAK inhibitors

Biologic

• IL 4/13 inhibitors

• IL 13 inhibitors

• IL 31 inhibitors

Example of IL 4/13 inhibitors used for atopic dermatitis?

Dupixent

MOA of IL 4/13 inhibitors?

Inhibits IL-4 and IL-13 cytokine induced inflammatory responses, including the release of proinflammatory cytokines, chemokines, nitric oxide, and IgE

Dupixent adult dosing?

Adult and PEDs

LD → one dose

MD → dose every 14 days

How is Dupixent supplied?

Pen and syringe

SUBQ
IL 4/13 INHIBITOR

Warnings/Precautions for Dupixent?

Do not use to treat acute asthma symptoms including bronchospasm, reduce corticosteroid dose gradually, avoid abrupt discontinuation, helminth infection → stop therapy until infection resolves

AE → Injection site reactions, dry/red/itchy eyes, herpes simplex infections

EYES

No monitoring

Examples of IL 13 Inhibitors used for atopic dermatitis?

Adbry

Ebglyss

MOA of IL 13 inhibitors?

mAB IgG4 inhibits the bioactivity of IL-13 and prevents the release of proinflammatory cytokines, chemokines, and IgE

Adbry dosing?

Adult and PEDs

LD → one dose

MD → dose every 14 days

Ages 12 and older

How is Adbry supplied?

Syringe only

SUBQ
IL-13 INHIBITOR

Ebglyss dosing?

Adult and PEDs

LD → dose at week 0 and 2, then dose every 2 weeks until 16 weeks

MD → dose every 28 days

Ages 12 and older

How is Ebglyss supplied?

Syringe and Pen

SUBQ

IL 13 INHIBITOR

Warnings / Precautions for IL 13 Inhibitors?

Helminth infection occurs → stop therapy until infection resolves, hypersensitivity reactions

AE → conjunctivitis, keratoconjunctivitis, keratitis, injection site reactions

Examples of IL 31 inhibitors for atopic dermatitis?

Nemluvio

MOA of IL 31 inhibitors?

IgG2 mAB inhibits IL-31 signaling via binding selectively to IL-31 RA, thus inhibiting the release of proinflammatory cytokines and chemokines

Nemluvio dosing?

Adult and PEDs

LD → single dose

MD → dose every 28 days, can decrease the dose every 8 weeks

Ages 12 and older

How is Nemluvio supplied?

Pen

SUBQ
IL 31 INHIBITOR

Examples of Janus Kinases (JAK) inhibitors for atopic dermatitis?

Ciblinqo

Opzelura

Rinvoq

Ciblinqo dosing?

Adult and PEDs

Dose daily

Ages 12 and older

How is Ciblinqo supplied?

Oral tablets

ORAL
JAK INHIBITOR

Opzelura dosing?

Adult and PEDs

Apply a thin layer topically twice daily

Ages 2 and older

How is Opzelura supplied?

Cream

TOPICAL
JAK INHIBITOR

Rinvoq dosing?

Oral tablet dose daily

Ages 12 and older

How is Rinvoq supplied?

Oral tablet

Ages 12 and older

Black box warning for JAK inhibitors?

Increased risk of all cause mortality, major adverse cardiovascular events (MACE) thrombosis and malignancy

How are JAK inhibitors stored and administered?

Stored → room temp, in the original container

Administration → give missed dose asap within 12 hours of schedule dose, if <12hrs of schedule dose just skip and resume regular dosing schedule

Take with or without food, swallow whole

What medications are not immunosuppressive for atopic dermatitis?

Dupixent

Adbry

Ebglyss

Nemluvio

What baseline labs are required before starting immunosuppressive therapy?

TB screening → treat ≥1 month before starting if positive

HBV → refer to hepatology; consider prophylaxis for reactivation

HCV → refer to hepatology

HIV → refer to infectious disease

How should immunosuppressive therapy be managed during infection or illness?

Hold medication if febrile or signs of infection (URI, COVID, flu)

Hold if on antibiotics/antivirals/antifungals

Seek medical evaluation → notify specialist if severe symptoms

How should immunosuppressive therapy be managed around surgery?

Hold before and after procedures to promote wound healing

Timing varies by procedure and specialist

Typically resume → ~14 days after surgery unless otherwise directed

Which vaccines are contraindicated with immunosuppressive therapy?

Live vaccines →

MMR

Varicella

Intranasal influenza

Rotavirus

Yellow fever

Why is adherence important with biologic therapies (missed doses)?

Missed doses → risk of anti-drug antibody formation

Leads to decrease in effectiveness / loss of response

Risk ~2–26% → (up to ~52% with Remicade)

General advice for injectable medication storage?

Store in refrigerator

Do not freeze

Protect from light

Do not shake

Consult individual package inserts for → min. time out of fridge prior to injection, max time at room temp, allowable temp

Pen vs Syringe?

Pen → easier to use, needle hidden, less control, can misfire

Syringe → more control, needle visible, may be better for low BMI

What are the steps for subcutaneous injection administration?

Let medication warm to room temp

Check drug, dose, expiration, and inspect solution

Gather supplies and wash hands

Clean injection site (thigh, abdomen, upper arm)

Insert needle / place auto-injector (pinch skin if needed)

Administer medication

Dispose in sharps container

What drugs can be used with PEDs atopic dermatitis?

ALL atopic dermatitis drugs have a PEDs formulation