Psoriatic arthritis improved on risankizumab: does the presence of psoriatic arthritis mean a drug approved for psoriatic arthritis has to be prescribed?

KEYWORDS:

• Psoriasis
• psoriatic arthritis
• biologic agent
• FDA approval
• risankizumab

1. Introduction

Psoriasis is a systemic chronic inflammatory disease, and its inflammation may affect multiple systems. Many factors should be considered when choosing a treatment for moderate-to-severe psoriasis; one of which is coexistent psoriatic arthritis [1,2]. Psoriatic arthritis is a frequent comorbidity, and the treatment of these two conditions overlap due to similarities in the underlying molecular-mediated pathophysiology [1]. Some psoriasis treatments are also approved for the treatment of psoriatic arthritis, and some are not. However, lack of FDA approval for psoriatic arthritis in an anti-inflammatory treatment approved for psoriasis does not necessarily mean the treatment would be ineffective in treating psoriatic arthritis [1,2].

Risankizumab, a humanized IgG monoclonal antibody that targets the p19 subunit of IL-23, received FDA approval for the treatment of moderate-to-severe plaque psoriasis in 2019, and recently received approval for the treatment of psoriatic arthritis [2]. We report the case of a patient who achieved an excellent clinical response in both psoriasis and psoriatic arthritis symptoms with risankizumab before risankizumab was approved for psoriatic arthritis. This case illustrates that the effectiveness of the drug, which is not determined by approval status, can be a driving factor in treating psoriasis in patients who also have psoriatic arthritis.

2. Case report/case presentation

The patient was a 45-year-old female with a history of plaque psoriasis since age 34 and joint pain since age 35. While prior cutaneous lesions were primarily limited to the scalp, ears, and perianal area, she presented with an acute flare, with extensive plaques covering the aforementioned locations and also the trunk and extremities. Body surface area (BSA) involvement was 10% and Physician Global Assessment (PGA) was 3 (moderate lesions). Prior prescribed treatments included topical clobetasol solution, betamethasone, and tacrolimus ointment, none of which reportedly provided much relief. She had a family history of both psoriasis and psoriatic arthritis in her mother and maternal grandfather.

The patient was referred to rheumatology and presented for initial consult 6 months after starting treatment with risankizumab. Although improved, she had a history of swelling and pain of her left wrist and proximal interphalangeal joints, in addition to inflammatory back pain and stiffness, which were worse in the morning. These specific symptoms first presented three years prior and progressively worsened over time, however they improved after treatment with risankizumab. Upon subsequent X-Ray, degenerative changes of the lumbosacral spine were present. Due to overall concern for psoriatic arthritis, she was initiated on 600–800 mg twice daily, in addition to 200–400 mg as needed, ibuprofen.

3. Discussion and conclusion

Biologics are immunomodulatory therapeutics which target specific cytokines implicated in the pathogenesis of psoriasis [1]. Currently, there are 11 FDA approved biologics and are a mainstay in the treatment of moderate-to-severe psoriasis [1]. Some, not all, of these are also approved for the treatment of psoriatic arthritis (and, conversely, a treatment may be approved for psoriatic arthritis and not psoriasis). While risankizumab, an IL-23 antagonist, was not yet FDA-approved for the treatment of psoriatic arthritis at the time we treated our patient, the drug was, not surprisingly, effective for both her psoriasis and psoriatic arthritis.

The IL-17/IL-23 axis contributes to the underlying pathogenesis of both plaque psoriasis and psoriatic arthritis. In psoriatic arthritis, IL-23 stimulates CD3+, CD4-, CD8-, ROR γδ, and IL-23 R+ resident T-cells. The stimulation of these T-cells subsequently induces production of inflammatory cytokines TNF-α, IL-17, and IL-22, which promote inflammation, bone erosion, and osteoproliferation [1,3–5]. In plaque psoriasis, IL-23, produced by myeloid dendritic cells, can be found in abundance in psoriatic skin lesions. IL-23 specifically maintains Th17 cells, which are a major source for IL-17, whose downstream pro-inflammatory cascade operate via an ACT 1 adaptor protein dependent and independent pathway [1,3].

Drugs that block the IL17/IL23 pathway can be expected to be effective for both psoriasis and psoriatic arthritis. Two biologic agents approved for psoriasis, including brodalumab and tildrakizumab, are also not approved for psoriatic arthritis. Tildrakizumab improved psoriatic arthritis symptoms in phase II (NCT02980692), and brodalumab was better than placebo for psoriatic arthritis symptoms in phase III trials (NCT02029495) [6,7]. While FDA approval guarantees that a drug is more effective on average than is placebo, lack of approval does not necessarily mean that a drug is ineffective.

FDA approval for psoriasis and psoriatic arthritis occurs via two separate 10-month standard review processes. Historically, psoriasis and psoriatic arthritis drugs tend to be approved several months following publication of phase III trial results (Table 1). Phase III brodalumab trial results were published in February 2021 and is expected to be approved in 2022 [8]. Several cases in the literature also report psoriatic arthritis improvement with biologic agents that are not yet FDA-approved for psoriatic arthritis (Table 2). Many patients had long-standing histories of recalcitrant psoriatic arthritis, and all achieved lasting clearance of both psoriasis and psoriatic arthritis symptoms.

Table 1. FDA approval timeline for psoriasis and psoriatic arthritis drugs

Class of Drugs	Drug	Psoriasis Approval	Phase 3 PsA Trial	PsA Application Submission Date	PsA Approval	Phase 3 Journal Publication Date
TNF-alpha inhibitors	Cimzia (certolizumab)	5/28/18	RAPID-PsA	11/28/12	9/27/13	12/4/13
	Enbrel (etanercept)	4/30/04		n/a	1/15/02	7/6/04
	Humira (adalimumab)	10/4/05	ADEPT	n/a	1/22/08	1/30/07
	Remicade (infliximab)	9/26/06	IMPACT	12/1/04	5/13/05	4/7/05
	Simponi (golimumab)		GO-REVEAL	n/a	4/24/09	5/30/09
IL-12/23 inhibitor	Stelara (ustekinumab)	9/25/09	PSUMMIT	11/21/12	9/23/13	8/31/13
IL-17 inhibitors	Cosentyx (secukinumab)	1/21/15	FUTURE	3/18/15	1/15/16	9/19/15
	Siliq (brodalumab)	2/15/17	AMVISION			2/1/21
	Taltz (ixekizumab)	3/22/16	SPIRIT	1/31/17	12/1/17	6/10/17
IL-23 inhibitors	Ilumya (tildrakizumab)	5/21/18	INSPIRE
	Skyrizi (risankizumab)	4/23/19	KEEPsAKE	4/7/21
	Tremfya (guselkumab)	7/13/17	DISCOVER	9/13/19	7/14/20	4/10/20
CD80/86:CD28 inhibitor	Orencia (abatacept)		ASTRAEA	8/31/16	7/6/17	5/4/17
JAK inhibitor	Xeljanz (tofacitinib)		OPAL	2/22/17	12/14/17	10/19/17

Abbreviations: CD – cluster of differentiation; IL – interleukin; JAK – janus kinase; PsA – psoriatic arthritis; TNF – tumor necrosis factor

Table 2. Case reports of PsA improvement with biologic agents that are not yet FDA-approved for PsA

Publication	Sex	Age	Presentation	Treatment	Clinical outcome	Response time
Ward et al [9].	Female	40	Plaque psoriasis (24 years) and PsA (<1 year)	Risankizumab	Psoriasis clearing, joint disease control	Unknown
Ismail et al [10].	Male	40	Psoriatic nail dystrophy and PsA	Tildrakizumab	Nail dystrophy and PsA improvement	12 weeks
Singh et al [11].	Male	50	Moderate to severe plaque psoriasis and PsA (15 years)	Brodalumab	Psoriasis clearing, PsA asymptomatic	10 weeks
Rivera-Oyola et al [12].	Male	30	Severe psoriasis and PsA	Brodalumab	PASI-100, improved joint pain	4 weeks
Pinter et al [13].	Female	49	Plaque psoriasis (29 years), psoriatic arthritis (21 years)	Brodalumab	PASI reduced by 90% to 0.8, PsA asymptomatic	6 weeks
Pinter et al [13].	Male	61	Plaque psoriasis (13 years) and PsA (10 years)	Brodalumab	Regression of plaques, PsA asymptomatic	2 weeks

Abbreviations: PsA – psoriatic arthritis, PASI-100 – Psoriasis Area and Severity Index 100% reduction.

4. Expert opinion

Although multiple clinical trials are required for investigational therapeutics to receive approval, patients treated during these trials may not reflect real-world populations [14]. Specifically, the meticulous study designs and controlled environments constructed for clinical trials may not accurately assess real-world efficacy. However, in four recently completed real-world studies, IL-23 inhibitors, including risankizumab, guselkumab, and tildrakizumab, all improved the clinical severity of psoriatic patients, even in cases of multi-treatment failure, suggesting their utility as reliable therapeutics even in cases of hard to manage disease [15–17].

Psoriasis is a chronic inflammatory disease that may affect multiple systems and many patients with psoriatic arthritis have preexisting skin manifestations. Although management can involve different specialties, the treatment of both the skin and joint manifestations can overlap due to the similar underlying molecular pathophysiology. Many factors need to be considered when choosing psoriasis treatments. If a physician believes a particular treatment that is not approved for psoriatic arthritis is the best treatment for a patient’s skin lesions, the physician may not necessarily need to change the choice of treatment to a drug that is FDA-approved for psoriatic arthritis if the patient has psoriatic arthritis [18]. While FDA approval guarantees a drug is effective, lack of approval does not mean the drug is ineffective [18]. Thus, when selecting an appropriate treatment, while it may be helpful to consider the underlying mechanism and FDA approval, for many patients, including our case, choosing what we think is best for the skin may be entirely appropriate, as medications that clear the inflammation in the skin are also likely to improve inflammation in the joints, with or without FDA approval [18].

Author contributions

R Singh, AM Brown, WH Chan, MA Farr, S Venkataraman, and SR Feldman conceptualized and wrote the original draft. RS, MA Farr, and S Venkataraman edited the draft and created the tables. R Singh, AM Brown, and SR Feldman reviewed and edited the draft and tables.

Declaration of interest

SR Feldman has received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Baxter, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, Taro, AbbVie, Cosmederm, Anacor, Astellas, Janssen, Lilly, Merck, Merz, Novartis, Regeneron, Sanofi, Novan, Parion, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation. He is founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patients’ adherence to treatment. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have been a consultant and investigator for numerous companies that make biologics for psoriasis. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Ethical approval

Study approval was not required for this study in accordance with local/national guidelines. Written informed consent was obtained from the patient for publication of the details of her medical case. No images of the participants were obtained.

Data availability statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Additional information

Funding

This paper was not funded.