Biological

therapy in
psoriasis
Aya AlOrbani, MD

Lecturer of Dermatology, Cairo

University
Kasr AlAiny Psoriasis Unit (KAPU)
 • Male
• 35 years old
• Severe psoriasis

Cyclosporine (exceeded 1 year use)

Methotrexate (Adverse effects)
Acitretin
Phototherapy
 • Male
• 35 years old
• Severe psoriasis

Cyclosporine (exceeded 1 year use)

Methotrexate (Adverse effects)
Acitretin
Phototherapy
 • Male
• 35 years old
• Severe psoriasis

Cyclosporine (exceeded 1 year use)

Methotrexate (Adverse effects)
Acitretin
Phototherapy
 • Male
• 35 years old
• Severe psoriasis

Cyclosporine (exceeded 1 year use)

Methotrexate (Adverse effects)
Acitretin
Phototherapy
 • Male
• 35 years old
• Severe psoriasis

Cyclosporine (exceeded 1 year use)

Methotrexate (Adverse effects)
Acitretin
Phototherapy
 • Male
• 67 years old
• Creatinine elevated

Cyclosporine
Methotrexate
Acitretin
Phototherapy
 • Male
• 67 years old
• Creatinine elevated

Cyclosporine
Methotrexate
Acitretin
Phototherapy
 • Male
• 67 years old
• Creatinine elevated

Cyclosporine
Methotrexate
Acitretin
Phototherapy
 • Male
• 67 years old
• Creatinine elevated

Cyclosporine
Methotrexate
Acitretin
Phototherapy
 • Male
• 67 years old
• Creatinine elevated

Cyclosporine
Methotrexate
Acitretin
Phototherapy
• 46-year-old female
• PASI: 15.4
• PsA with painful
mutilations in
interphalangeal joints
Cyclosporine
Methotrexate
Acitretin
Phototherapy
• 46-year-old female
• PASI: 15.4
• PsA with painful
mutilations in
interphalangeal joints
Cyclosporine
Methotrexate
Acitretin
Phototherapy
• 46-year-old female
• PASI: 15.4
• PsA with painful
mutilations in
interphalangeal joints
Cyclosporine
Methotrexate
Acitretin
Phototherapy
Biologics
 :Chronic severe psoriasis
PASI or DLQI more than 10

That have failed treatment or

been intolerant to at least two
systemic therapies
What are
biological
?drugs

Agents that can specifically target an immune

mediator
 IL-12/23 IL-23 inhibitor
inhibitor Approved for both psoriasis and
psoriatic arthritis
Ustekinumab (except Risankizumab : psoriasis only) Guselkumab
(Stelara) ( Tremfya)
Tildrakizumab (Ilumya)
Risankizumab (Skyrizi)

TNF-alpha
inhibitors
IL-17 inhibitors

Etanercept(Enbrel)
Adalimumab (Humira) Secukinumab (Cosentyx)
Infliximab (Remicade) Ixekizumab (Taltz)
Certolizumab (Cimzia) Brodalumab (Siliq) : blocks
Golimumab (Simponi) receptor
 Nomenclature
• -cept = human receptor fusion protein

• -ab = monoclonal antibody:

 -ximab = chimeric (Animal origin)
-umab = human
-zumab = humanized
 TNF-alpha inhibitors

Infliximab Adalimumab Etanercept Certolizumab

)Ramicade( )Humira( (Enbrel) (Cimzia)
 TNF in psoriasis

TNF inhibitors:
Infliximab
Adalimumab
Etanercept
Certolizumab

KC proliferation ++
angiogenesis ++
cytokine production ++
cell trafficking ++
Infliximab and Adalimumab: Action
Infliximab and Adalimumab: Action

Infliximab Adalimumab

Chimeric Human
Monoclonal Ab
Etanercept: Action

Soluble TNF
Etanercept: Action

Recombinant Soluble TNF

Fusion protein
Certolizumab

Humanized
Fab fragment
 Anti-TNF: Dosage
Infliximab Adalimumab Etanercept
!! Infusion reaction
IV infusion SC
•The infusion
SC
is administered
Starting over50a mg
Dose: period
2/w of 3
for
5 mg/kg 80 mg thehours.
first week  40
two months‡
weeks 0, 2, and 6  then mg the second week  40
•During the infusion, Maintenance
and for one Dose:
hour after,
50 mg  1/w
every 6-8 weeks mg every other week
monitor
•Pre-treatment with oral antihistamines,
paracetamol and/or glucocorticosteroids
 Anti-TNF: Dosage
Certolizumab
SC
.mg (given as 2 injections of 200 mg each) every other week 400
 Non TNF-alpha inhibitors

IL-12/23 inhibitors IL-17 inhibitors IL-23 inhibitors

Ustekinumab Secukinumab Guselkumab

)Stelara( (Cosentyx) (Tremfya)
Risankizumab
(Skyrizi)
IL-12 IL-23

Ustekinumab
IL-12/23 inhibitor

Guselkumab
IL-23 inhibitor

Risankizumab
IL-23 inhibitor
Secukinumab IL-17A
IL-17 inhibitor
 Non-TNF : Dosage
Ustekinumab

≤100 kg: 45 mg SC  4 weeks later give 45 mg  45 mg q12weeks.

>100 kg: 90 mg SC  4 weeks later give 90 mg  90 mg SC q12weeks.

 Non-TNF : Dosage
Secukinumab

300 mg SC once weekly for 5 weeks 

every 4 weeks
 Non-TNF : Dosage
Guselkumab

100 mg SC at weeks 0 and 4, followed by a

maintenance dose every 8 weeks.
 Non-TNF : Dosage
Risankizumab

150 mg SC at Week 0, Week 4, followed by a

maintenance dose every 12 weeks starting at
Week 16
No consensus on duration of biologics
treatment
More targeted therapy
BUT

!Not without complications

 Anti-TNF: Side effects and contraindications
Loss of efficacy over time 
Side effects Absolute
Absolute contraindications
contraindications
Neutralizing antibodies • Cardiac insufficiency NYHA grade III – IV
(esp. infliximab:
•Infusion reactions (Infliximab) 10-30%,• Pre-existing tuberculosis
least with etanercept) • Active chronic hepatitis B
• Infections: TB/ bacterial/ fungal
• HBV reactivation Relative contraindications
Relative contraindications
• Malignancy
Controversial
• Malignancies (NMSCs/ ± lymphomas) • PUVA > 200 treatments
Anti-TNF-α agents may induce
• Autoimmune diseases
•Demyelinating disease
psoriatic eruptions
• Demyelinating processes:or
MSworsen
• pre-existing
Hepatitis C psoriatic skin
• Congestive heart failure
disease
 Non-TNF: Side effects
Ustekinumab Secukinumab
)anti IL-12/23( (anti IL-17)

• Infections: RTI, • Infections: Candidiasis,

nasopharyngitis Nasopharyngitis

• Exacerbation of inflammatory
• Hypersensitivity reactions bowel disease
(e.g. angioedema,
anaphylaxis) • Hypersensitivity reactions
 Non-TNF: Side effects
Guselkumab
)anti IL-23(
• Infections: RTI, gastroenteritis, (fungal infections less
encountered compared to anti IL 17)

• Diarrhea

• Urticaria

• Injection site erythema

 Non-TNF: Side effects
Risankizumab
)anti IL-23(

• Infections: RTI

• Headache

• Fatigue

• Injection site reaction

 Non-TNF: Contraindications
• Active serious infection including TB and Hepatitis

• Patients with risk factors for developing non-melanoma

skin cancer
Do not give concomitant live
vaccines
Pre biologics
history and
work-up
 Pre-therapy history

Demyelinating disease

Recent
immunization TB
Malignancy Cardiac disease
Ultraviolet therapy
Hepatitis

Inflammatory bowel
disease
 Prebiologics labs/investigations

Routine labs Chest x-ray

• CBC Tuberculin or Quantiferon
• ESR, CRP
• ASOT Echocardiography
• Liver function tests
• HBsAg OR anti-HB core
• Urea and
antibody (to detect carrier
creatinine
state)
• ANA
• HCV antibodies ELISA

• HCV / HBV RNA PCR

• QuantiFERON®-TB Gold test should be done
(more specific and sensitive than tuberculin
test)
Biologics in special
situations
• Hepatitis
• TB
• Inflammatory bowel disease
• Pregnancy
 Special situations: chronic hepatitis
HCV HBV
Anti-TNF
Safety profile may be .Reports of reactivation
acceptable (Close follow with Avoid in HBsAg positive
a hepatologist) .patients
en Anti-IL-23/12, anti-23
V
Reactivation
and anti IL-17
.Insufficient data
 Special situations: TB
• Anti-TNF: Risk of TB reactivation (may be less with
etanercept)

• Non-TNF: SAFER
– Ustekinumab: appears to be safer than anti-TNF biologics
– Secukinumab: No reports of TB reactivation
 Special situations: TB
Baseline Tuberculin/Quantiferon
Chest Xray

Active TB Manage TB, withhold therapy

INH for 9 months, or INH + RFP for 3 months or

Latent TB RFP for 4 months; start biologics 1 month after

Annual screening with tuberculin and quantiferon

No TB
test in those considered at high risk of TB exposure
 Special situations: Inflammatory bowel disease

Association with psoriasis not uncommon

• Tumor necrosis factor inhibitors Effective

treatment
• Ustekinumab options

• Interleukin-17 inhibitor: Secukinumab Could

exacerbate
• Etanercept IBD
 Special situations: Pediatric use

• Etanercept: approved for patients 4 years and above

• Adalimumab: approved for patients 4 years and above
• Ustekinumab: approved for patients 6 years and above
• Secukinumab: approved for patients 6 years and above
 Special situations: Pregnancy

• Certolizumab  Safest, can be used throughout pregnancy

(does not cross the placenta in significant amounts)
• Etanercept up to 30 – 32 weeks
• Othersup to 20 weeks

• No live vaccinations for 6 months after birth due to the increased risk of
infection.
 Combinations
TNF-α inhibitors + Methotrexate

• esp. infliximab & adalimumab + Methotrexate

 ↓ formation of anti-drug antibodies (ADA)
• Etarnecept + Methotrexate  enhance
effectiveness
Which biologic to choose for
your patient?
 Cardiac ejection Fraction >50%
 No History of Demyelinating disease
 PUVA < 200 sessions
 QuantIFERON or Tuberclin negative
 No Hepatitis B* or HIV
 Cardiac ejection Fraction <50%
 History of Demyelinating disease
 PUVA >200 sessions +/- Cyclosporine
 QuantIFERON or Tuberclin positive
 Inactive Hepatitis B or C

History of resistance to TNF Ustekinumab

monoclonal Ab’s biologics Secukinumab

Yes No Guselkumab

Infliximab
Etanercept Adalimumab
Ustekinumab Etanercept Biologics Algorithm
Secukinumab Certolizumab
Guselkumab Ustekinumab
Secukinumab
Guselkumab
 Biosimilars in psoriasis
• Biosimilar: biological product that is highly
similar to an approved biologic (i.e.,
originator or reference) product

• Biosimilars may offer less expensive

treatment options for patients with
psoriasis
 Biosimilars in psoriasis
• Etanercept biosimilars: Erelzi™, Brenzys®
• Adalimumab biosimilars: Amgevita®, Hadlima®,
Hyrimoz®, Idacio®, Hulio® , Cyltezo
• Infliximab biosimilars: Inflectra®, Renflexis®, Avsola®,
Omvyence™, Remsima™
Biosimilars in psoriasis

• Interchangeability??

• More studies
needed
 • Male
• 35 years old
• Exceeded 1 year
of Cyclosporine
• Adverse effects
with MTX
•Phototherapy not
applicable
 Prebiologics history /labs/investigations
Routine labs
CBC, ESR, CRP, ASOT, Liver function tests, Urea
History and creatinine, ANA
TB
Cardiac
Cardiac disease
Echocardiography
Hepatitis
Inflammatory bowel disease TB
Demyelinating disease Chest x-ray
Recent immunization Quantiferon
Malignancy
Hepatitis
UV therapy
• HBsAg OR anti-HB core antibody (to detect
carrier state)
• HCV antibodies ELISA
• HCV / HBV RNA PCR
 Cardiac ejection Fraction >50%
 No History of Demyelinating disease
 PUVA < 200 sessions
 QuantIFERON or Tuberclin negative
 No Hepatitis B* or HIV
 Cardiac ejection Fraction <50%
 History of Demyelinating disease
 PUVA >200 sessions +/- Cyclosporine
 QuantIFERON or Tuberclin positive
 Inactive Hepatitis B or C

History of resistance to TNF Ustekinumab

monoclonal Ab’s biologics Secukinumab

Yes No Guselkumab

Infliximab
Etanercept Adalimumab
Ustekinumab Etanercept Biologics Algorithm
Secukinumab Certolizumab
Guselkumab Ustekinumab
Secukinumab
Guselkumab
 • Male
• 35 years old
• Exceeded 1 year
of Cyclosporine
• Adverse effects
with MTX
•Phototherapy not
applicable

doses of 5
secukinumab
 • Male
• 67 years old
•H/O of treatment with
MTX  Good response
but stopped when
renal functions were
elevated

2 doses of
guselkumab
 6 doses of
secukinumab

• 46-year-old female
• PASI: 15.4
• PsA with painful mutilations
in interphalangeal joints
 Anti-TNF Anti-IL-12/23 Anti-IL-17 Anti-IL-23
Infliximab Adalimumab Etanercept Ustekinumab Secukinumab Guselkumab
Risankizumab
Monoclonal antibody Fusion ptn Monoclonal antibody
IV SC

Work-up (Routine labs /echo/chest x-ray/quantiferon/HBsAg/HCV Ab)

Infusion Infections : RTI, •Fungal •RTI
reaction
nasopharyngitis Infections
• INFECTIONS (TB, HBV reactivation) •Exacerbati
• Neutralizing antibodies on of IBD
• CHF
• Malignancy??
Do not give concomitant live vaccines
Biologics : Special situations
Certolizumab preferable

Etanercept, Adalimumab, Ustekinumab, Secukinumab

HCV: may be acceptable. Avoid in HBV

TB reactivation reported. Avoid TNF inhibitors

IBD: Avoid secukinumab and etanercept

Give TNF inhibitors or ustekinumab
!Thank you