Biologics in psoriasis: Challenges and management

ACHAIKI IATRIKI | 2020; 39(3): 129–132


Kerasia-Maria Plachouri, Sophia Georgiou

Department of Dermatology, University of Patras, Greece

Received: 13 March 2020; Accepted: 2 April 2020

Corresponding author: Kerasia-Maria Plachouri, University General Hospital of Patras, Rio 265 04, Tel.: +30 694 66 39 340, E-mail:

Key words: Psoriasis, biologics, chronic infection, malignancy, pregnancy


Psoriasis is a chronic inflammatory disease, with a complex therapeutic management [1]. Biologics are modern agents that target key molecules in the pathogenetic pathways of psoriasis, with impressive therapeutic results [2]. However, due to their partially immunosuppressive profile, several problems may occur in cases of concomitant conditions, such as infections, past malignancy or pregnancy. This article focuses on the management of biologics’ administration in these challenging occasions frequently encountered in standard clinical practice.

Biologics and hepatitis

Screening for Hepatitis B and C before the initiation of anti-TNF (Tumor Necrosis Factor) therapy is mandatory, with assessment of the following parameters: For hepatitis B, detection of HBsAg, anti-Hbc and anti-HBs, and in case of positive HbsAg or anti-HBc, HBV-DNA measurement (Hepatitis B Virus), while for hepatitis C, detection of anti-HCV (Hepatitis C Virus), and if positive, HCV-RNA measurement [3-4]. These recommendations are based on the fact that TNF-a is known to play an important role in the elimination of HBV from liver cells, therefore a therapy with anti-TNF-a agents could have a modulating effect in the course of HBV-infection with potential reactivation of the infection [3] (Table 1).

HBV vaccination is recommended for the non-infected or not immune patients before treatment initiation [3]. No biologic treatment is allowed in patients with acute HBV [4]. Patients with chronic HBV hepatitis and inactive carriers (HbsAg +, anti-HBc +, HBV-DNA< 2000 IU/ml, normal transferase levels), can receive anti-TNF treatment, as long as antiviral prophylaxis with agents such as entecavir or tenofovir is administered 2-4 weeks before treatment initiation and for a time period of up to 6-12 months after treatment end [3,5]. Occult carriers (HBsAg -, anti-Hbc +, anti-Hbs -, HBV-DNA < 200 IU/mL or undetectable) should be either very closely monitored or prescribed antiviral treatment [5]. Biologic therapy is allowed in patients with a history of HBV infection, however only under careful monitoring [4].

Anti-TNF therapy is relatively safer in patients with chronic HCV compared to patients with chronic HBV [3]. However, even in this case, regular patient follow-up (liver function parameters and HCV-RNA viral load every 3-6 months) is suggested by some dermatologic societies [3-4]. An important aspect that should be taken into consideration when it comes to HCV-positive patients, is the role of the new direct-acting antiviral (DAA) IFN-free therapies, that can result in extremely satisfactory outcomes, with almost complete and long-lasting clearance of HCV-RNA in patients’ serum [6]. When it comes to possible interactions of biologics and DAAs, data is extremely limited [6]. However, data on the metabolic and elimination profile of the latter rather advocate against clinically significant pharmacokinetic interactions between these two drug categories [6].

As far as IL-12/23- (Ustekinumab) is concerned, antiviral prophylaxis is suggested for patients with HBsAg +/anti-HBc + before treatment initiation, during treatment, and up to 6 months after therapy discontinuation, always under careful monitoring [3,7]. When it comes to the management of HBsAg -/ anti-HBs-/ anti-HBc + positive patients, they should either undergo very careful monitoring or receive antiviral prophylaxis [5]. This is based on the fact that IL-12 is known to play a crucial role in modulating an immune response against intracellular pathogens, and therefore it can be assumed that reactivation of HBV could be expected under IL-12/23-inhibitors [3] (Table 1). Clinical data on secukinumab in psoriatic patients with an HBV infection are rather scarce [4] (Table 1). Both HBsAg-positive and HBsAg-negative/HBcAb-positive psoriasis patients as well as HBsAg-negative/HBcAb-positive patients with a positive viral load at baseline are under the risk of virus reactivation while on immunosuppressive treatment, therefore regular monitoring of viral load and antiviral prophylaxis is suggested [5]. Overall, no sufficient data are available concerning HCV and ustekinumab or secukinumab in psoriatic patients, for safe assumptions to be made [3].

Biologics and tuberculosis

Another infectious complication that physicians often have to face when dealing with biologics is tuberculosis. Tuberculosis screening (tuberculin skin test (TST) or interferon gamma release assay (IGRA) and a chest X-ray) before treatment initiation is strongly recommended for such patients [4]. In case of unclear findings, prophylaxis with isoniazid for a period of 9 months is necessary, with initiation of the anti-TNF agent at least 1 month after isoniazid initiation [4].

Given that a small risk of disease activation is also present in patients under ustekinumab, the aforementioned measures concerning tuberculosis screening and prophylaxis apply in this case [8]. When it comes to secukinumab, although no data of latent tuberculosis reactivation have been published so far, screening as well as appropriate prophylaxis –if necessary- are to be recommended [9].

Biologics and malignancy

Malignancy in patients under a biologic treatment is another common therapeutic challenge. According to the British Guidelines for Dermatology concerning the use of biologics in psoriatic patients, a history of malignancy is not considered to be an absolute contraindication [10]. The administration of anti-TNF therapy is, however, advisable to occur after consulting the treating oncologist, and especially if the malignancy was diagnosed and treated < 5 years prior to therapy initiation [10]. Some societies tend to favorize ustekinumab or secukinumab over TNF-inhibitors in patients with a history of malignancy [4], while others do not differentiate between these two categories, especially if the diagnosis and treatment of a past solid malignancy took place >5 years prior to the planned biologic treatment [11].

When it comes to the use of ustekinumab or secukinumab in patients with a history of malignancy, published data are too limited to allow for safe assumptions [12]. Preliminary data seem to indicate that the incidence of recurring malignancy for both agents is comparable to that of the general population [13-14]; however clinical studies in larger patient cohorts as well as meta-analyses of long-term real-life data are necessary to adequately estimate the malignancy-associated safety of these agents [15].

Biologics and hiv

A therapeutic dilemma that physicians commonly have to face is the administration of biologics in HIV-infected (Human Immunodeficiency Virus) patients. The administration of biologics in HIV-infected patients poses several challenges, since these patients are already under virus-mediated immunosuppression [4]. Furthermore, HIV-positive patients tend to be excluded from clinical trials, and for this reason, the management of TNF-inhibitors in this group is mostly based on case reports and case series [4]. Most of the data derived from these cases involve the use of etanercept and infliximab, which –at least in psoriatic patients-resulted in good therapeutic outcomes without alterations of the CD4 count or viral load and without additional opportunistic infections [4,8]. Cases of successful use of adalimumab without additional complications are also published in the literature, but are substantially fewer compared to those assessing etanercept or infliximab treatment [8]. Reports on certolizumab pegol and HIV-infected patients are not available at this point. It is important to point out that the administration of biologic agents should always take place under the supervision of HIV specialists to avoid disease-related complications [8].

Preliminary data on ustekinumab demonstrate a satisfactory safety profile as well as good therapeutic outcomes in psoriatic patients [16]. Interestingly, it has been proven that in several cases, CD4 count and viral load not only remained stable, but also showed improvement [16]. Generally, fewer cases of infectious complications are documented under ustekinumab compared to anti-TNF agents, however among the possible explanations is the fact that the latter are available over a longer period of time than IL-12/23-inhibitors [16].

No sufficient data on secukinumab or any other IL-17-inhibitor, are available at this point.

Biologics and pregnancy

Pregnant patients are another population group, where the use of biologics should be carefully managed. When it comes to the safety profile of anti-TNF agents in pregnancy, no clear indication of embryotoxicity or teratogenicity under adalimumab, infliximab, etanercept and certolizumab pegol compared to the general population has been documented so far [16]. Αll aforementioned anti-TNF agents are classified by the Food and Drug Administration (FDA) as pregnancy class B medications [17].

In order to avoid neonatal infection due to active placental transfer of these agents during pregnancy, that can then be detected in infants up to the 6th month of life, it is advisable to discontinue therapy with infliximab or adalimumab in the 20th pregnancy week, otherwise infants should not receive any kind of live-attenuated vaccination up to the 6th month after delivery [4,17-18]. Due to differences in the transport rate of etanercept and certolizumab pegol, the former can be continued up to the 32nd week while the latter throughout pregnancy [4,17-18]. However, given that studies describing pregnancy-associated drug-specific harm tendencies have also been published -even though their findings often lack statistical significance-, each case should be individually assessed, taking into consideration the risk and benefit ratio for the affected patient [19]. These harm tendencies refer mostly to major congenital malformations, such as vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities, as well as unfavorable pregnancy outcomes, including preterm delivery, low birth weight, spontaneous/elective abortion and adverse maternal measures [19].

Clinical data concerning the use of IL-12/23-inhibitors in pregnancy are rather scarce; although some publications with limited patient numbers report uncomplicated pregnancy outcomes under ustekinumab (FDA pregnancy class B), reports on spontaneous abortions during such treatments are also published in the literature [20]. Studies on IL-17 agents are also limited. Preliminary information derived from a global safety database and concerning 292 secukinumab-exposed pregnancies, describes no increased abortion rates under secukinumab (FDA pregnancy class B) compared to the general population, however no safe suggestions can be made on the ground of insufficient data [21].

Overall, despite the undoubtable benefits that accompany the administration of biologics in serious chronic diseases like chronic plaque psoriasis, that until recently were proven refractory to the conventional immunosuppressive treatments, physicians still have to face challenges and dilemmas concerning their use, particularly when confronted with special conditions, such as pre-existing chronic infections or unprecedented events in the form of a pregnancy. The conduction of clinical trials in larger patient cohorts, as well as findings derived from isolated case series or case reports, are necessary in order to enrich existing knowledge on how to adequately manage these potentially complex situations.

Conflict of interest disclosure

None to declare

Declaration of funding sources

None to declare


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