Saudi consensus statement on biologic treatment of chronic plaque psoriasis (2020)

Figures & data

Figure 1. Use of treatment goals to guide therapy.

Table 1. Laboratory screening prior to initiation of a biologic treatment (10,12,22–34).

Parameter	Baseline	Follow-up^a	Annual screening
CBC with differential	✓	6 months	✓
RFT	✓	6 months	✓
LFT	✓	6 months	✓
HBV/HCV	✓	–	✓
HIV	✓	–	✓
Pregnancy Test	✓	–	–
TST or IGRA	✓	–	✓
Chest X-ray	✓	–	–

^aOr if clinically indicated. CBC: complete blood count; RFT: renal function tests; LFT: liver function tests; HBV: hepatitis B virus; HCV: hepatitis C virus; TST: tuberculin skin test; IGRA: interferon-gamma release assay.

Table 2. Screening for comorbidities (10,12,22–34).

Parameter

Lipid Profile

Uric Acid

HbA1c/FBS

Autoantibodies (anti-nuclear antibodies, anti-nuclear double-strand DNA antibodies)*

HbA1c: glycated hemoglobin; FBS: fasting blood sugar.

*If clinically indicated.

Table 3. Biologic agents and biosimilars available for the treatment of psoriasis in Saudi Arabia.

Generic	Brand	Pharmacology classification	Strengths and formulations	FDA approved	SFDA Registration (38)	Approved indication
Adalimumab (23)	Humira	Anti-tumor necrosis factor	40 mg/0.8 ml – SQ injection	✓	✓	Plaque psoriasis, Psoriatic arthritis
Certolizumab pegol (24)	Cimzia	Anti-tumor necrosis factor	200 mg/mL – SQ injection	✓	✓	Plaque psoriasis, Psoriatic arthritis
Etanercept (31)	Enbrel	Anti-tumor necrosis factor	50 mg/mL – SQ injection	✓	✓	Plaque psoriasis, Psoriatic arthritis
Guselkumab (28)	Tremfya	Anti-IL-23/IL-39 antibodies	100 mg/mL – SQ injection	✓	✓	Plaque psoriasis
Infliximab (22)	Remicade	Anti-tumor necrosis factor	100 mg/vial – intravenous infusion	✓	✓	Plaque psoriasis, Psoriatic arthritis
Infliximab (39)	Remsima^a	Anti-tumor necrosis factor	100 mg/vial – intravenous infusion	✓	✓	Plaque psoriasis, Psoriatic arthritis
Ixekizumab (27)	Taltz	Anti-IL-17 antibodies	80 mg/mL – SQ injection	✓	✓	Plaque psoriasis, Psoriatic arthritis
Risankizumab (30)	Skyrizi	Anti-IL-23/IL-39 antibodies	75 mg/0.83 ml – SQ injection	✓	✓	Plaque psoriasis
Secukinumab (26)	Cosentyx	Anti-IL-17 antibodies	150 mg/mL – SQ injection	✓	✓	Plaque psoriasis, Psoriatic arthritis
Ustekinumab (25)	Stelara	Anti-IL-12/IL-23 antibody	45 mg/0.5 ml or 90 mg/mL SQ injection	✓	✓	Plaque psoriasis, Psoriatic arthritis

Therapies are listed in alphabetical order.

^aBiosimilar.

Table 4. Dosing schemes, type of antibody, efficacy, and half-life of biologic agents/biosimilars available for the treatment of psoriasis in Saudi Arabia.

Generic	Brand	Dose		Type of Antibody	Efficacy		Half-life (days)
		Loading	Maintenance		Induction efficacy	Long-term efficacy
Adalimumab (41,42)	Humira	80 mg SubQ at weeks 0, then 40 mg SubQ at week 1	40 mg SubQ every other week	Fully Human	PASI 90 (W16): 45%	PASI 90 (W160): 50%	14
Certolizumab pegol (43)	Cimzia	400 mg SubQ at weeks 0, 2, and 4	200 or 400 mg SubQ every other week	Humanized	PASI 90 (W16 − 200 mg): 35.8% PASI 90 (W16 − 400 mg): 43.6%	PASI 75 (W48 − 200 mg): 81% PASI 75 (W48 − 400 mg) = 83%	14
Etanercept (44,45)	Enbrel	50 mg SubQ twice weekly for 12 Weeks	50 mg SubQ once weekly	Protein fusion receptor	PASI 90 (W12 − 50 mg BIW): 21%	PASI 90 (W72): 27%	3.5
Guselkumab (46,47)	Tremfya	100 mg SubQ at weeks 0, Week 4	100 mg SubQ every 8 weeks	Fully Human	PASI 90 (W16): 73.3% (Voyage 1) PASI 90 (W16): 70% (Voyage 2)	PASI 90 (W48): 76.3% (Voyage 1) PASI 90 (W24): 75.2% (Voyage 2)	18
Infliximab (48–51)	Remicade	5 mg/kg IV over at least 2 h at weeks 0, 2, and 6	5 mg/kg IV over at least 2 h every 8 weeks^a	Chimeric monoclonal antibody to TNF	PASI 90 (W10): 57%	PASI 90 (W50): 45%	10–15
Ixekizumab (52)	Taltz	160 mg SubQ at week 0, followed by 80 mg SubQ every 2 weeks for 3 months	80 mg SubQ every 4 weeks	Humanized	PASI 90 (W12 – every 4 weeks): 59.7% (UNCOVER-2) PASI 90 (W12 – every 4 weeks): 65.3% (UNCOVER-3)	Not Available	13
Risankizumab (53)	Skyrizi	150 mg SubQ at Week 0, Week 4.	150 mg SubQ every 12 weeks	Humanized	PASI 90 (W16): 75.3% (UltIMMA-1) PASI 90 (W16): 74.8% (UltIMMA-2)	PASI 90 (W52): 81.9% (UltIMMA-1) PASI 90 (W52): 80.6% (UltIMMA-2)	28
Secukinumab (54)	Cosentyx	300 mg SubQ at weeks 0, 1, 2, 3, and 4	300 mg SubQ every 4 weeks	Fully Human	PASI 90 (W12 − 300 mg): 59.2% (ERASURE) PASI 90 (W12 − 300 mg): 54.2% (FIXTURE)	Not Available	27
Ustekinumab (55)	Stelara	100 kg or less; 45 mg SubQ initially and 4 weeks later >100 kg: 90 mg SubQ initially and 4 weeks later	100 kg or less: 45 mg every 12 weeks >100 kg: 90 mg every 12 weeks	Fully Human	PASI 90 (W16): 57.6%	PASI 90 (W52 − 45 mg): 45.9% PASI 90 (W52 − 90 mg): 55%	21

BIW: twice weekly; O\W: once weekly; IV: Intravenous; SubQ: subcutaneous.

Efficacy is reported based on the results of pivotal studies.

^aTime interval can be modified and dose per kg can be increased according to the patient's responses.

Table 5. Adverse event of biologic agents for the treatment of psoriasis.

Generic	Common	Serious	Rare
Adalimumab (23)	Injection site pain, injection site reaction, rash, headache, sinusitis, upper respiratory infection	Erythema multiforme, Stevens-Johnson syndrome, agranulocytosis, erythrocytosis, thrombocytopenia, thrombosis, hepatic failure, acute, hepatic necrosis, reactivation of hepatitis B, hepatosplenic T-cell lymphoma, herpes zoster, hypersensitivity reaction, malignant lymphoma, bone necrosis, subdural hematoma, bronchospasm, dyspnea, pleural effusion, tuberculosis, invasive fungal infection atrial fibrillation, cardiac arrest, cardiac dysrhythmia, chest pain, congestive heart failure, hypertensive encephalopathy	Demyelinating disease of central nervous system, peripheral demyelinating neuropathy, leukopenia, pancytopenia
Certolizumab pegol (24)	Arthralgia, urinary tract infectious disease, upper respiratory infection	Toxic epidermal necrolysis, Stevens-Johnson syndrome, urticaria, cardiac dysrhythmia, congestive heart failure, hypertensive heart disease, myocardial infarction, pericardial effusion, pericarditis, bowel obstruction, nephrotic syndrome, renal failure, malignant lymphoma, opportunistic infection	Hypersensitivity reaction, lupus erythematosus, demyelinating disease of central nervous system
Etanercept (31)	Injection site reaction, upper respiratory infection	Congestive heart failure, erythema multiforme, malignant melanoma, necrotizing fasciitis, primary cutaneous vasculitis, skin cancer, squamous cell carcinoma of skin, Stevens-Johnson syndrome, toxic epidermal necrolysis Malignant lymphoma, seizure, transverse myelitis, acute, optic neuritis	Aplastic anemia, leukemia, pancytopenia, reactivation of hepatitis B viral hepatitis, autoimmune hepatitis, tuberculosis, demyelinating disease of central nervous system, multiple sclerosis, peripheral demyelinating neuropathy
Guselkumab (28)	Bronchitis, upper respiratory infection	Anaphylaxis, hypersensitivity reaction Tuberculosis, infectious disease	–
Infliximab (22)	Rash, abdominal pain, nausea, headache, pharyngitis, sinusitis, upper respiratory infection, fatigue	Acute coronary syndrome, bradyarrhythmia, cardiac dysrhythmia, heart failure, hypertension, hypotension, myocardial infarction, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, hemolytic anemia, malignant lymphoma, leukopenia, neutropenia, pancytopenia, thrombocytopenia, cerebrovascular accident, demyelinating disease of central nervous system, cervical cancer, pulmonary edema, tuberculosis, cancer, histoplasmosis, infectious disease, infusion reaction	Myocardial ischemia, systemic vasculitis, autoimmune hepatitis, hepatic failure, acute, hepatitis, hepatotoxicity, allergic reaction, anaphylaxis, hepatosplenic T-cell lymphoma
Ixekizumab (27)	Neutropenia, injection site reaction, upper respiratory infection	Hypersensitivity reaction, infectious disease	Candidiasis
Risankizumab (7,30)	Injection site reaction, tinea, antibody development, headache, upper respiratory infection Fatigue	Infectious disease, tuberculosis	–
Secukinumab (26)	Nasopharyngitis, diarrhea	Anaphylaxis, Infectious disease	Exacerbation, ulcerative colitis, inflammatory bowel disease, candidiasis
Ustekinumab (25)	Erythema at injection site, abdominal pain, headache, bronchitis, nasopharyngitis, sinusitis, upper respiratory infection Fever, infectious disease	Skin cancer, non-melanoma, posterior reversible encephalopathy syndrome, cryptogenic organizing pneumonia, interstitial pneumonia, pulmonary eosinophilia, angioedema, cancer, infectious disease	Diverticulitis, anaphylaxis, hypersensitivity reaction, herpes zoster with ophthalmic complication

Figure 2. Management algorithm for the application of biologic therapy for the management of psoriasis. The order or treatments does not indicate priority. *16 weeks for skin and 24 weeks for joint disease. **IL-12/23 agonist used for patients with peripheral arthritis only.

Table 6. Summary of recommendations for biologic therapy options in pregnancy.

	Certolizumab pegol	Etanercept	Adalimumab	Infliximab	IL-12/IL-23 inhibitors	IL-23 inhibitors	IL-17 inhibitors
Pregnancy	Most Preferred	Alternative to Certolizumab if not available	Higher placental transfer	Higher placental transfer	Safety is uncertain	Safety is unknown	Safety is uncertain

Table 7. Summary of recommendations for choice of biologic therapy in pediatrics and adolescents.

	FDA approved for moderate-to-severe pediatric plaque psoriasis	Doses in children (subcutaneous)
Adalimumab	≥4 years (15)	10–<15 kg
		10 mg every other week
		15–<30 kg
		20 mg every other week
		≥30 kg
		40 mg every other week
Etanercept	≥4 years (13)	0.8 mg/kg weekly, with a maximum of 50 mg per week
Ustekinumab	≥6 years (75)	<60 kg
		0.75 mg/kg
		≥60 kg
		as adult
		The dosing frequency is the same as in adults at weeks 0 and 4, then every 12 weeks thereafter
Ixekizumab (27)	≥6 years	<25 kg
		40 mg at day 0 then 20 mg every 4 weeks
		25–50 kg
		80 mg at day 0 then 40 mg every 4 weeks
		>50 kg
		160 mg (two 80 mg syringes) at day 0 then 80 mg every 4 weeks
Secukinumab (26)	≥6 years	<50 kg
		75 mg at weeks 0,1,2,3,4 followed by monthly maintenance doses.
		≥50 kg
		150 mg (can be increased to 300 mg) at weeks 0, 1, 2, 3, 4 followed by monthly maintenance doses

Hamadah IR, Al Raddadi AA, Bahamdan KA, et al. Saudi practical guidelines on biologic treatment of psoriasis. J Dermatolog Treat. 2015;26(3):223–229.

 PubMed Web of Science ®Google Scholar

Smith CH, Jabbar-Lopez ZK, Yiu ZZ, et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017. Br J Dermatol. 2017;177(3):628–636.

 PubMed Web of Science ®Google Scholar

Gelfand JM, Armstrong AW, Bell S, et al. National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: version 2-advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments. J Am Acad Dermatol. 2021;84(5):1254–1268.

 PubMed Web of Science ®Google Scholar

Product Information. HUMIRA subcutaneous injection, adalimumab subcutaneous injection. North Chicago (IL): AbbVie Inc (per FDA); 2015.

 Google Scholar

Product Information. CIMZIA subcutaneous injection, Certolizumab pegol subcutaneous injection. Smyrna (GA): UCB Inc (per manufacturer); 2019.

 Google Scholar

Product Information. Enbrel subcutaneous injection solution, etanercept subcutaneous injection solution. Thousand Oaks (CA): Amgen Inc (per FDA); 2015.

 Google Scholar

Product Information. TREMFYA subcutaneous injection, guselkumab subcutaneous injection. Horsham (PA): Janssen Biotech Inc (per FDA); 2019.

 Google Scholar

Product Information. REMICADE lyophilized concentrate for intravenous injection, infliximab lyophilized concentrate for intravenous injection. Horsham (PA): Janssen Biotech, Inc (per FDA); 2011.

 Google Scholar

Product Information. REMSIMA lyophilized concentrate for intravenous injection, infliximab lyophilized concentrate for intravenous injection. Incheon, South Korea: Celltrion Healthcare Co Ltd; 2016.

 Google Scholar

Product Information. TALTZ subcutaneous injection, ixekizumab subcutaneous injection. Indianapolis (IN): Eli Lilly and Company (per manufacturer); 2019.

 Google Scholar

Product Information. SKYRIZI subcutaneous injection, risankizumab-RZAA subcutaneous injection. North Chicago (IL): AbbVie Inc (per FDA); 2019.

 Google Scholar

Product Information. COSENTYX subcutaneous injection, secukinumab subcutaneous injection. East Hanover (NJ): Novartis Pharmaceuticals Corporation (per FDA); 2018.

 Google Scholar

Product Information. STELARA subcutaneous injection, intravenous injection, ustekinumab subcutaneous injection, intravenous injection. Horsham (PA): Janssen Biotech Inc (per FDA); 2019.

 Google Scholar

Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58(1):106–115.

 PubMed Web of Science ®Google Scholar

Gordon K, Papp K, Poulin Y, et al. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol. 2012;66(2):241–251.

 PubMed Web of Science ®Google Scholar

Gottlieb AB, Blauvelt A, Thaçi D, et al. Certolizumab pegol for the treatment of chronic plaque psoriasis: results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2). J Am Acad Dermatol. 2018;79(2):302–314.e6.

 PubMed Web of Science ®Google Scholar

Leonardi CL, Powers JL, Matheson RT, et al. Etanercept as monotherapy in patients with psoriasis. N Engl J Med. 2003;349(21):2014–2022.

 PubMed Web of Science ®Google Scholar

Leonardi C, Strober B, Gottlieb AB, et al. Long-term safety and efficacy of etanercept in patients with psoriasis: an open-label study. J Drugs Dermatol. 2010;9(8):928–937.

 PubMed Web of Science ®Google Scholar

Blauvelt A, Papp KA, Griffiths CE, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76(3):405–417.

 PubMed Web of Science ®Google Scholar

Reich K, Armstrong AW, Foley P, et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76(3):418–431.

 PubMed Web of Science ®Google Scholar

Griffiths CE, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–551.

 PubMed Web of Science ®Google Scholar

Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650–661.

 PubMed Web of Science ®Google Scholar

Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis–results of two phase 3 trials. N Engl J Med. 2014;371(4):326–338.

 PubMed Web of Science ®Google Scholar

Langley RG, Lebwohl M, Krueger GG, et al. Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol. 2015;172(5):1371–1383.

 PubMed Web of Science ®Google Scholar

Furue M, Kadono T. Psoriasis: behind the scenes. J Dermatol. 2016;43(1):4–8.

 PubMed Web of Science ®Google Scholar

NICE Pathway Systemic biological therapy for psoriasis 2019. Available from: https://pathways.nice.org.uk/pathways/psoriasis (accessed December 2020).

 Google Scholar

Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019;80(4):1029–1072.

 PubMed Web of Science ®Google Scholar

Product Information. STELARA subcutaneous injection, intravenous injection, ustekinumab subcutaneous injection, intravenous injection. Janssen Biotech Inc (per EMA); 2020. Available from: https://wwwemaeuropaeu/en/medicines/human/EPAR/stelara

 Google Scholar