Table 3.

Listed reasons for the exclusion of biological treatments for psoriasis management (government protocol)

Government argument	Argument critiques/questioning	Author	Reference
High cost	“Despite the lack of a vital threat, psoriasis is highly important to the national economy and to those who have the disease”	Radtke and Augustin, 2008, Clin Dermatol	54
	Indirect costs (productivity loss, including costs of long-term sick leave and disability pension) are more substantial than direct costs in Sweden	Norlin et al, 2015, Acta Derm Venereol	55
	Biological drug prescription was associated with an increase in the use of anti-infective drugs and with a reduction in the use of psychoactive drugs	Le Moigne et al, 2014, J Eur Acad Dermatol Venereol	56
Adverse reactions	Questions about the safety of other systemic drugs, especially methotrexate and cyclosporin, have limited the ability of dermatologists in many countries to adequately treat moderate-to-severe psoriasis	Nast A, 2013, Arch Dermatol Res	57
	Opportunistic infections were reported infrequently among 19,041 patients who were treated with adalimumab	Burmester et al, 2009, Ann Rheum Dis	58
	A register from the British Society of Rheumatology compared 11,798 anti-TNF-α-treated patients and 3,598 nonbiological DMARD-treated patients and demonstrated that anti-TNF-α therapy is associated with a small overall risk of serious infections (42 vs 32 cases/1,000 patient-years)	Galloway et al, 2011, Rheumatology (Oxford)	59
	Evidence from global clinical trials in 3,010 anti-TNF-α-treated psoriasis patients demonstrated that psoriasis patients had 1.7 serious infections per 100 patient-years, which is much lower than the frequencies observed for rheumatoid arthritis and Crohn’s disease (treatment of both of these conditions with anti-TNF-α is approved by specific protocols in Brazil)	Burmester et al, 2013, Ann Rheum Dis	60
	Tuberculosis screening resulted in a reduction of the incidence of the disease by 84%	Perez et al, 2005, Ann Rheum Dis	61
	A meta-analysis of six controlled trials with ustekinumab revealed no statistically significant differences in adverse effects between 90 mg of ustekinumab, 45 mg of ustekinumab, and placebo	Liu et al, 2014, Chin Med Sci J	62
Placebo-controlled studies	Adalimumab was compared to methotrexate and placebo in a double-blind, randomized comparative 16-week study. Efficacy was assessed based on the PASI 75 response, which was faster (8 weeks) and superior in the adalimumab group.	Saurat et al, 2011, Br J Dermatol	63
	A Cochrane meta-analysis of patients from 163 randomized controlled trials (50,010) found no statistically significant differences in serious adverse events and serious infections between biological and nonbiological DMARDs.	Singh et al, 2011, Cochrane Database Syst Rev	64
	For the comparisons of adalimumab vs methotrexate, infliximab vs methotrexate, ustekinumab vs methotrexate, and etanercept vs acitretin, there is predominantly a low strength of evidence that favors the individual biological agent vs the nonbiological agent	Lee et al, 2012, Agency for Healthcare Research and Quality (US)	65
Short follow-up	Treatment with ustekinumab for up to 5 years was safe, and adverse event rates were generally comparable between the ustekinumab and placebo groups	Langley et al, 2014, Br J Dermatol	66

Abbreviations: DMARD, disease-modifying antirheumatic drug; PASI, psoriasis area and severity index; TNF, tumor necrosis factor.