Risankizumab,a therapeutic alternative for psoriasis in people living with HIV

Abstract

The management of psoriasis in individuals with human immunodeficiency virus (HIV) presents a unique challenge, marked by a more severe progression and limited efficacy of first- and second-line treatments. Although conventional systemic therapies might be considered, these agents are immunosuppressants, making their use challenging in people living with HIV (PLHIV). Biologic agents are frequently used in individuals with moderate-to-severe psoriasis, but their efficacy and safety data in PLHIV are very limited, as this patient group tends to be excluded from clinical trials. Risankizumab is a selective interleukin-23 (IL-23) inhibitor that has demonstrated a favourable safety profile and high efficacy in long-term studies and clinical practice. This current case report presents two clinical cases of PLHIV with plaque psoriasis who were effectively treated with the biologic agent risankizumab, with no reported safety issues. Although there are limited data on the use of biologics in PLHIV, this case series suggests that IL-23 inhibitors, namely risankizumab, might be a valuable therapeutic option for this population. Additional research and larger studies are needed to gain a more comprehensive understanding of the long-term safety and efficacy of IL-23 inhibitors in individuals affected by HIV.

Introduction

While the prevalence of psoriasis in people living with human immunodeficiency virus (HIV) is similar to that of the general population, its progression tends to be more severe in individuals with HIV.^1,2 In fact, HIV infection can be both a trigger and an exacerbating factor for psoriasis.^3,4

Managing psoriasis in people living with HIV (PLHIV) presents a unique challenge. Topical therapies, highly active antiretroviral therapy (HAART) and phototherapy are the first-line therapeutic options in these individuals, with oral retinoids used as second-line treatment. ⁵ However, in this patient group, the disease course is frequently marked by its severity and treatment resistance; therefore, these therapeutic approaches often prove insufficient in effectively controlling the clinical manifestations of psoriasis. ⁶

Thus, other systemic therapies, namely conventional systemic agents (methotrexate and cyclosporine) and biologics, might be considered. ⁵ Methotrexate and cyclosporine are associated with various adverse effects, including end-organ toxicity and drug–drug interactions, requiring close laboratory monitoring. ⁷ Furthermore, these agents are immunosuppressants, making their use challenging in PLHIV, particularly those not receiving HAART, who already have a compromised immune status.^5,6 Biologic agents are commonly used in patients with moderate-to-severe psoriasis, with excellent long-term and short-term efficacy and a favourable safety profile compared to conventional systemic therapies.^8,9 However, the efficacy and safety data for biologics in PLHIV are very limited, as this patient group tends to be excluded from clinical trials.^10,11

This current report presents a case series of two HIV-positive individuals with psoriasis who were effectively treated with risankizumab, a selective interleukin-23 (IL-23) inhibitor, without encountering any safety issues.

Case reports

In March 2020, a 34-year-old woman (case 1) with severe plaque psoriasis and HIV infection with poor adherence to HAART presented to the Department of Dermatology, Centro Hospitalar Universitário de Santo António, Porto, Portugal. In addition, the patient was obese and had untreated dyslipidaemia. There was no family history of psoriasis and no personal history of psoriatic arthritis. She presented due to the worsening of her psoriasis, with a body surface area (BSA) of approximately 20% and a psoriasis area and severity index (PASI) of 24, along with an inadequate response to topical therapy. Her HIV viral load was 1230 copies/ml and her CD4 count was 12 cells/μl. Considering the patient's clinical context, the recommended dose of risankizumab (150 mg administered as a subcutaneous injection at week 0, week 4 and every 12 weeks thereafter) was initiated. After 8 weeks of treatment, she achieved a PASI 100 response; and no significant adverse events were reported during a 168-week follow-up. After initiating risankizumab and experiencing subsequent improvement in her skin condition, she started HAART (800/150/200/10 mg of darunavir/cobicistat/emtricitabine/tenofovir plus 50 mg of dolutegravir taken orally once daily) with good adherence, resulting in an undetectable viral load and an increase in her CD4 count to over 300 cells/μl.

In October 2022, a 35-year-old man (case 2) with a long-standing history of plaque psoriasis and HIV infection managed with HAART (50/300 mg of dolutegravir/lamivudine taken orally once daily) presented to the Department of Dermatology, Centro Hospitalar Universitário de Santo António, Porto, Portugal. There was no personal history of other comorbidities and no family history of psoriasis. He presented due to the worsening of his psoriasis, with a BSA of approximately 22% and a PASI of 21, along with an inadequate response to topical therapies and 25 mg acitretin taken orally once daily. His HIV viral load was undetectable and his CD4 count was 512 cells/μl. Starting with the recommend risankizumab dose (150 mg administered as a subcutaneous injection at week 0, week 4 and every 12 weeks thereafter), a PASI 100 response was achieved at week 8 (Figure 1); and no significant adverse events were reported during a 56-week follow-up. He maintained an undetectable viral load and a CD4 count within the same range as pre-treatment.

Figure 1.

Photographs of a 35-year-old male patient (case 2) who presented with worsening plaque psoriasis and a concomitant HIV infection managed with highly active antiretroviral therapy showing the psoriatic plaques before starting treatment with risankizumab (W0) and after 8 weeks of therapy (W8). The colour version of this figure is available at: http://imr.sagepub.com.

Both patients provided written informed consent for both their treatment and the publication of this case report. It should be noted that the treatment decisions were made in cooperation with an HIV specialist. The reporting of these two cases conforms to the CARE guidelines. ¹²

Discussion

Interleukin-23 plays a major role in the pathogenesis of psoriasis by promoting the differentiation and proliferation of T helper 17 cells, which, upon activation, produce several pro-inflammatory cytokines such as IL-17, the most important effector cytokine in psoriasis.^13,14 Risankizumab binds with high affinity to IL-23 via its unique p19 subunit, effectively inhibiting the inflammatory cascade triggered by this key cytokine. ¹⁵

Due to their immunosuppressive potential, the long-term use of biologics in immunocompromised individuals (such as PLHIV) raises some safety concerns, including an increased risk of infections.^16,17 Although data remain limited, regarding the use of biologics in the HIV population, existing evidence supports the therapeutic efficacy and safety of these agents, namely IL-23, IL-17 and tumour necrosis factor (TNF) inhibitors, for treating HIV-positive individuals with moderate-to-severe psoriasis.^18–20 Furthermore, evidence suggests that selective inhibition of IL-23, particularly through its unique p19 subunit, provides a more favourable safety profile when compared with inhibiting other inflammatory cytokines such as IL-17 and TNF. ¹⁷ In fact, a recent meta-analysis concluded that risankizumab has the most favourable long-term benefit–risk profile compared with other biologic agents for the treatment of psoriasis. ²¹

Seven cases of PLHIV with psoriasis treated with risankizumab have been reported (Table 1).^22–24 In all seven cases, the treatment with risankizumab was effective, well-tolerated and no significant adverse events were recorded.^22–24 In addition, a PLHIV with psoriasis treated with guselkumab, another IL-23 inhibitor, has been reported (Table 1). ²⁵ The treatment proved effective, with no reported adverse events, and both viral load and CD4 count remained stable throughout the treatment period. ²⁵

Table 1.

Case reports of people living with human immunodeficiency virus (HIV) and concomitant psoriasis treated with interleukin-23 inhibitors.

Study	Sex/Age	Therapy	HAART	CD4 count, cells/μl		HIV viral load, copies/ml		Significant AE	PASI
				Pre-treatment	Post-treatment	Pre-treatment	Post-treatment		Pre-treatment	Post-treatment
Rob & Rozsypal 2022 22	M/36	Risankizumab	Yes	N/S	630	Undetectable	Undetectable	None	10.3	0 (after 12 weeks)
Maliyar et al. 2023 23	M/36	Risankizumab	Yes	1461	1225	Undetectable	Undetectable	None	5.4	0 (after 5 months)
	M/58	Risankizumab	Yes	831	926	Undetectable	Undetectable	None	4.0	1.6 (after 3 doses)
Orsini et al. 2023 24	M/53	Risankizumab	Yes	N/S	N/S	N/S	NVR	None	22	0 (after 16 weeks)
	M/32	Risankizumab	Yes	N/S	N/S	N/S	NVR	None	30	0 (after 16 weeks)
	M/58	Risankizumab	Yes	439	N/S	Undetectable	NVR	None	20	1 (after 16 weeks)
	M/53	Risankizumab	Yes	N/S	N/S	Undetectable	NVR	None	10	0 (after 16 weeks)
Bartos et al. 2018 25	M/51	Guselkumab	Yes	54	41	29	Undetectable	None	N/S	0 (after 6 months)
This current case series	F/34	Risankizumab	No	12	> 300	1230	Undetectable	None	24	0 (after 8 weeks)
	M/35	Risankizumab	Yes	512	Stable	Undetectable	Undetectable	None	21	0 (after 8 weeks)

HAART, highly active antiretroviral therapy; AE, adverse events; PASI, psoriasis area and severity index; M, male; N/S, not specified; NVR, no viral reactivation; F, female.

Despite limited data on the use of biologics in PLHIV, this case series suggests that IL-23 inhibitors, such as risankizumab, might be a valuable therapeutic choice for this particular population. The positive balance between benefits and risks, observed in both long-term studies and case reports of PLHIV (Table 1), reinforces their potential as effective and safe treatments for psoriasis in individuals with HIV.^22–25

Further research and larger studies involving this specific cohort are needed to better understand the long-term safety and efficacy of IL-23 inhibitors in people affected by HIV. Nevertheless, these findings contribute to the progression and evolution of psoriasis management in immunocompromised individuals, providing hope for better outcomes in this challenging patient group.

In conclusion, managing psoriasis in PLHIV poses a unique challenge due to the frequently severe course of the disease and the limitations of conventional therapies in this patient group. These two current patients, one with poor adherence to HAART and the other effectively managed with HAART, experienced significant improvement of their psoriasis with risankizumab therapy, with no significant adverse events reported during follow-ups of 168 and 56 weeks, respectively.