Targeted treatment of psoriasis with adalimumab: a critical appraisal based on a systematic review of the literature

Figures & data

Table 1 Pharmacokinetic properties of adalimumab^40–43

Parameter	Value
Absolute bioavailability	64%
Time to maximum concentration	131 ± 56 hours
Maximum serum concentration	4.7 ± 1.6 μg/mL
Volume of distribution	4.7 to 6.0 L
Steady-state through concentration	~5 mg/mL
Total body clearance	0.18–0.27 ml/min
Terminal half-life	~14 days
Time to
Initial response	1–7 days
Peak response Within	3 months

Table 2 Efficacy and long-term effectiveness of adalimumab in randomized controlled trials

Reference	Study design	Intervention (n); comparator (n)	Study population % females; age range disease severity at baseline1	Primary efficacy assessment	Results Psoriasis vulgaris: PASI 50, 75, 90 response rate Psoriatic arthritis: ACR 204, 50, 70 response rate
					Adalimumab		Comparator
Plaque psoriasis
Gordon 2006^Citation48	12-week, double-blind, placebo-controlled RCT; open-label extension until week 60	Adalimumab (A) 40 mg weekly (n = 50) vs A 40 mg eow2 (n = 46) vs placebo (n = 52)	33% 20–86 years 16	PASI 75 at week 12	A 40 mg/week week 12 88%, 80%, 48% week 60 64%, 64%, 48%	A 40 mg/eow week 12 76%, 53%, 24% week 60 66%, 56%, 33%	Placebo week 12 n.r., 4%, n.r.
Menter 2008^Citation49	16-week, double-blind, placebo-controlled RCT; open-label extension until week 52; rerandomization of responders at week 33	A 40 mg eow (n = 814) vs placebo (n = 398)	34% mean: 45 years 19	PASI 75 at week 16 Loss of response2 between week 33 and 52	Week 16 n.r., 71%, 45% Loss of response3 within 19 weeks after discontinuation: 5%	Placebo Week 16 n.r., 7%,2% Loss of response: 28%
Saurat 2008^Citation50	16-week, double-blind RCT adalimumab vs methotrexate vs placebo	A 40 mg eow (n = 108) vs methotrexate initially 7.5 mg orally/week, increased as needed to 25 mg (n = 110) vs placebo (n = 53)	34% mean 41 years 19	PASI 75 at week 16	88%, 80%, 52%	Methotrexate 62%, 36%, 14% Placebo 30%, 19%, 11%
Psoriatic arthritis
Mease 2005^Citation57 Gladman 2007^Citation56 Mease 2008^Citation58	24-week, double-blind, placebo-controlled RCT, open-label extension study	A 40 mg eow (n = 151) vs placebo (n = 162)	44% mean 49 years 14/25	ACR 204 response at week 12 Mean change in modified total Sharp score at week 24	ACR 20, 50, 70 response rates Week 12: 58%, 36%, 20% Week 48 (n = 151): 56%, 44%, 30% Week 104 (n = 281): 57%, 45%, 30% Sharp score (structural joint damage) Week 24: −0.1 Week 48: +0.1 Week 144: +0.5	ACR response rates week 12 14%, 4%, 1% Sharp score Week 24: +1.0
Genovese 2007^Citation59	12-week, double-blind, placebo-controlled RCT, open-label extension until week 24	A 40 mg eow (n = 51) vs placebo (n = 49)	46% mean 49 years 18/27	ACR 20 response at week 12	39%, 25%, 14%	16%, 2%, 0%

1 Notes: Psoriasis vulgaris: mean PASI at baseline, Psoriatic arthritis: mean number of swollen/tender joints;

2 every other week;

3 <PASI 50 and ≥6 Point increase in PASI;

4 American College of Rheumatology 20% improvement; n.r. not reported.

Table 3 Effectiveness of adalimumab for psoriasis

Reference	Study design	Study population n % females; age range baseline severity	Prior antipsoriatic treatment	Concurrent treatment	Results (effectiveness)
Papoutsaki 2007^Citation62	Prospective open-label uncontrolled study to assess the effectiveness of adalimumab 40 mg/week in patients with plaque psoriasis not responding to all other biologics approved	n = 30 33% 30–75 years mean PASI 16.4	other biologics and conventional treatments approved for psoriasis	No other systemic treatments allowed. No information on concurrent topical therapy	Week 12 PASI 50/75/90: 90%/87%/70% Week 24 PASI 50/75/90: 83%/83%/77% Psoriatic arthritis (n = 19) Mean HAQ week 0 vs week 24: 1.0 vs 0.2
Heiberg 2008^Citation63	Prospective register-based study to assess the comparative effectiveness of anti-TNFα therapy for PsA^Citation1	n = 150 patients receiving 172 treatment courses 37% mean 46 years	73% of patients were anti-TNFα therapy naïve	68% had concomitant MTX therapy	Drug withdrawal rates at 1 year: Adalimumab 14.3% Etanercept 24% Infliximab 25%
Van 2008^Citation64	Retrospective chart review to assess the long-term effectiveness of adalimumab 40mg/week in moderate-to-severe plaque psoriasis	n = 49 n.r. n.r. n.r.	76% had prior treatment with other anti-TNFα agents	n.r.	Proportion of patients “clear/almost clear”: After 3 months of treatment: 88% Sustained effectiveness after 12 months: 78%

Notes: One study also included patients with rheumatoid arthritis and ankylosing spondylitis which are not the scope of this paper; n.r., not reported.

Table 4 Safety and tolerability of adalimumab in randomized controlled trials

Reference	Monthly incidence rate of withdrawals and adverse events in patients receiving adalimumab			Lethal/life threatening adverse events (n)
	Adverse events (any)	Serious adverse events	Most frequent adverse events1
Gordon 2006^Citation48	25.2%2	1.9%2	Injection site pain 3.4%2 Increased blood triglycerides 2.3%2 Nausea 1.5%2 Dyspepsia 1.5%2	Malignant melanoma (n = 2) Breast cancer (n = 1) Gastric adenocarcinoma (n = 1) Coccidioidomycosis (n = 1) Recent onset latent tuberculosis (n = 1)
Menter 2008^Citation49	55.4%2	0.7%2	Injection site reaction 3.3%2 Upper respiratory tract infection 1.9%2 Nasopharyngitis 1.4%2 Headache 1.3%2	Basal cell carcinoma (n = 3) Squamous cell carcinoma (n = 3) Breast cancer (n = 1) Melanoma in situ (n = 1) Tuberculosis (n = 1) Congestive heart failure (n = 1)
Saurat 2008^Citation50	19.8%	0.5%	Nasopharyngitis 7.5% Headache 3.5% Arthralgia 1.5%	Pancreatitis (n = 1)
Mease 2005^Citation57	Not reported	0.6%2	Nasopharyngitis 1.8%2	Viral meningitis (n = 1)
Gladman 2007^Citation56			Injection site reaction 1.2 2	Myocardial infarction (n = 2)
Mease 2008^Citation58			Hypertension 0.9%2	Pulmonary embolism (n = 1) Peritoneal tuberculosis (n = 1) B-cell nonHodgkin lymphoma (n = 1) Nonmelanoma skin cancer (n = 3)
Genovese 2007^Citation59	18.9%2	0.7%2	Upper respiratory tract infection 4.9%2	Renal failure associated with rhabdomyolysis (n = 1)

1 Notes: Observed more frequently in an adalimumab group than placebo;

2 within double-blind treatment period.

Table 5 Rare adverse events of adalimumab in patients with psoriasis observed in clinical practice

Reference	Patient characteristics (n, sex, age, ethnicity)	Description of adverse reaction	Concurrent treatment	Authors’ conclusions about relationship of event with adalimumab
Berthelot 2005^Citation71	n = 1, female, 36 years, Hispanic	Two months after starting adalimumab painful ascending paresthesia, numbness of feet, weekness of lower extremities, progressing to complete foot drop; Complete resolution of symptoms 4 weeks after discontinuation of adalimumab.	Not reported	Association is plausible, because neurologic events suggestive of demyelination during treatment with other anti-TNFα agents have been observed.
Chung 2006^Citation72	n = 2, both men, age 55 and 40, ethnicity not reported	Two months after starting adalimumab rapid painless decrease of central vision one eye; MRI consistent with retrobulbar optic neuritis; complete resolution after discontinuation of adalimumab After one year of treatment with adalimumab progressive visual loss associated with pain on eye movement. MRI : optic neuritis and numerous CNS plaques of different ages. Gradual recovery after treatment with steroids. Patient continued adalimumab, follow-up examinations not reported	MTX, simvastatin, atenolol, aspirin, metformin, paroxetine, risperidone not reported	Optic neuritis and demyelinating diseases of the CNS appear to be associated with adalimumab therapy (as well as with other TNF antagonists).
Deng 2006^Citation78	n = 1, male, 54 years, ethnicity not reported	One year after initiation of adalimumab therapy development of annular erythematous papules on thighs and back, clinically and histologically consistent with interstitial granulomatous dermatitis. Resolution after discontinuation of adalimumab.	MTX	Adalimumab and other TNF antagonists may enhance the likelihood of developing interstitial granulomatous dermatitis in a subset of patients.
Wu 2008^Citation76	n = 1, male, 31 years, ethnicity not reported	One day after 2nd injection of adalimumab clinically significant signs of hyperglycemia in a patient with diabetes. Resolution after discontinuation. Reoccurrence after restart of adalimumab treatment with recurrent serum glucose elevation 3–4 days after adalimumab injection.	Glimepiride, metformin	In this case the association between adalimumab treatment and hyperglycemia obvious. Unclear whether an interaction with oral antidiabetics and/or genetic susceptibility may explain why hyperglycemia was not found in RCTs

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