A 46-year-old man presents for his first dermatology consultation for worsening symptoms of plaque psoriasis and recent-onset joint pain. He reports “painful aching” and swelling of his finger joints, which occasionally become stiff. He states he has a history of hyperlipidemia and mild hypertension.
Examination and diagnostic testing were notable for thick, pruritic, polycyclic salmon-colored plaques on the scalp, forehead, trunk, elbows, and knees bilaterally. Plaques are approximately 2 to 4 cm in size and cover approximately 30% of both lower limbs and dorsal trunk. No pigment changes were noted. Diffuse, bilateral swelling was noted on all digits, with erythema of the distal interphalangeal joints. Onycholysis, hyperkeratosis, and splinter hemorrhages were present in the nail beds.
This patient presents with severe psoriasis with cutaneous and nail involvement, including dactylitis, with a high suspicion of comorbid psoriatic arthritis.
A thorough discussion of treatment options incorporated both physician and patient priorities. Biologic drug treatment will be initiated with an interleukin (IL)-23 inhibitor.
Psoriasis is an inflammatory skin disease of autoimmune origin. Plaque psoriasis, its most common type, is characterized by red or silvery raised lesions, typically localized to the trunk, extensor surfaces of the limbs, scalp, and forehead.1
Psoriasis is not self-resolving. Treatment of mild cases may include topical medications and phototherapy. Systemic treatment options for moderate to severe psoriasis were previously limited to conventional immunosuppressive drugs, such as methotrexate and cyclosporine; these options have improved dramatically in the past 2 decades since the introduction of biologic drugs for psoriasis.1 This clinical case challenge presents a case of severe plaque psoriasis managed by biologic drug therapy.
A 46-year-old man presents with a chief complaint of worsening skin plaques and recent-onset joint pain with a 6-year history of worsening psoriasis and joint pain. His primary care provider (PCP) referred him to the dermatology practice of his hospital to evaluate whether phototherapy or systemic therapy was indicated.
The initial onset of mild psoriatic skin symptoms began at age 28 and was managed successfully with topical betamethasone valerate 0.1% cream. Approximately 6 years ago, his skin symptoms started to worsen. This patient also reported several weeks of new-onset stiffness and pain in the joints of his fingers and his heels bilaterally.
Past medical history includes hyperlipidemia, mild hypertension, and depression. Family history includes stroke, diabetes, and hypertension. He is unsure whether he has a family history of hypercholesterolemia and has not had any surgical procedures.
He has no known drug allergies.
His current medications include atorvastatin 40 mg once daily, lisinopril/hydrochlorothiazide 10 mg/12.5 mg once daily, paroxetine 20 mg once daily, and ibuprofen 400 mg every 6 hours as needed for joint pain. His PCP recently prescribed paroxetine for distress and depressive symptoms attributed to the worsening skin condition and joint pain which were affecting his quality of life. The patient admits to lapses not more than twice weekly in adherence to his medication regimen. His PCP also initiated a discussion with the patient regarding reducing his alcohol intake.
This patient is a busy franchise restaurant owner-operator by occupation who is not currently sexually active. By his report, he quit smoking cigarettes 2 years ago. Prior to quitting, he smoked approximately 1 pack of cigarettes a week for 10 years. He reports that he exercises twice a week and attempts to maintain a healthy diet. Over the past year, he reports intake of 13 to 15 alcoholic drinks during a typical week, noting that his alcohol intake increased during the COVID-19 pandemic. He denies any previous diagnosis of alcohol use disorder, but admits he engaged in discussion regarding the possibility of alcohol dependence with his PCP. He reports cannabis use on most days, citing skin pain secondary to psoriasis as his main rationale for cannabis use. He denies previous use of cannabidiol products as an alternative to cannabis but states he has considered doing so. He denies use of any other recreational or any illicit drugs.
In addition to feelings of depression, review of systems is positive for frequent diarrhea and abdominal bloating.
Examination and Diagnostic Tests
The patient is afebrile with a blood pressure of 138/83 mm Hg, respiratory rate of 17 breaths per minute, heart rate of 60 beats per minute; height of 5 feet 10 inches, weight of 198 lb, and BMI of 28.4.
Observation revealed a well-developed, well-nourished man appearing his stated age, with normal affect, alert, and oriented. Skin examination was notable for thick psoriatic plaques covering approximately 30% of both lower limbs (Figure) and dorsal trunk, left extensor elbow, scalp, and forehead. Scattered nail pitting and onycholysis were visible in his fingernails. His interphalangeal joints were moderately tender, with no gross joint deformity. Diffuse, bilateral swelling is in all digits, with erythema of several distal interphalangeal joints. Several toenails appear thickened and dystrophic.
Complete blood count results were notable for mildly elevated neutrophil count. Blood chemistry analysis revealed a decreased albumin level (3.1 g/dL) and hemoglobin A1c of 5.8. Lipid panel results revealed that his total cholesterol was 187 mg/dL, high-density lipoprotein cholesterol was 48 mg/dL, low-density lipoprotein was 109 mg/dL, and triglycerides was 152 mg/dL. Hepatic and renal function tests were within normal limits.
This patient has a Psoriasis Area and Severity Index (PASI) score of 17.6, which is indicative of severe psoriasis. He scores 3 on the 5-item Psoriasis Epidemiology Screening Tool (PEST), which is highly suggestive of psoriatic arthritis.
Clippings of his toenails were sent for histology and no fungal organisms were identified, confirming his nail changes also were due to psoriasis.
Treatment and Disease Course
Phototherapy and acitretin had been considered at the time of the patient’s referral for dermatology consultation. Acitretin, however, is less efficacious in plaque psoriasis than in other types of psoriasis.2 Considering this patient’s recent-onset joint pain and possibility of psoriatic arthritis, a disease-modifying antirheumatic drug (DMARD) was considered. Methotrexate is relatively contraindicated in this patient given his history of heavy alcohol consumption. Furthermore, this patient’s BMI indicates that he is overweight. While he does not meet full criteria for metabolic syndrome, he presents with some of its risk factors. Given these comorbidities, biologic drugs are preferred over conventional DMARDs as first-line therapy for severe psoriasis.3
Apremilast therapy was considered but rejected due to the potential of gastrointestinal intolerance and the desire for a more effective agent. Apremilast, a small molecule DMARD, is associated with possible weight loss and a rare risk for depression.4 While the possibility of weight loss was appealing, the patient specified that he wanted to avoid the risk of exacerbating his depressive symptoms.
The patient also expressed anxiety regarding the possible immunosuppressive effects of DMARDs, especially given the risk factors of his male sex and excessive weight in the context of the COVID-19 pandemic. The risk of SARS-CoV-2 infection in patients receiving DMARD therapy is similar to that in the general population5; however, given this patient’s apprehensions, it was explained that the class of anti-interleukin-23 (anti-IL-23) DMARDs would likely be particularly safe, even if somewhat slower acting than tumor necrosis factor (TNF) inhibitors or IL-17-inhibitors.
Patient adherence to previous at-home, self-administered medication regimens had been less than perfect. Therefore, the patient and physician collaboratively decided to introduce biologic treatment with tildrakizumab 100 mg administered at the physician’s office. Tildrakizumab is approved for administration by a health care professional. The dosage timing began at week 0, with the second dose at week 4, followed by 12-week intervals thereafter.6
The patient is given a referral to a rheumatology practice for further workup of possible psoriatic arthritis.
During follow-up at 47 weeks, the patient’s PASI score was 2.1, a nearly 90% reduction in PASI score (PASI90) compared with baseline measures. While tildrakizumab is not currently approved as a treatment for psoriatic arthritis, the patient noted his psoriatic arthritis symptoms of digit and heel pain also improved with use of tildrakizumab.7
However, the psoriasis began to recur and, at 64 weeks, PASI increased to 8.7. Given the initial good result with tildrakizumab, consideration was given to raising the dose of tildrakizumab to 200 mg. However, the likelihood of achieving PASI90 is not much different at the 200 mg dose compared with the 100 mg dose.7
The patient’s initial improvement suggested that IL-23 blockade was effective for him and tildrakizumab may have lost efficacy due to drug-specific antidrug antibody development, although the patient did not demonstrate an overt hypersensitivity reaction to this medication. Nevertheless, it was decided to discontinue tildrakizumab and switch to risankizumab, another drug in the IL-23 inhibitor class. Risankizumab is approved for both plaque psoriasis and active psoriatic arthritis in the United States.8 Guselkumab, another IL-23 inhibitor, also was considered.
Risankizumab, dosed every 12 weeks after initial loading doses, would be administered in the physician’s office for the time being. After the loading doses of 150 mg at week 0 and week 4, the patient received maintenance doses of 150 mg. At week 21, shortly before the time of this narrative, the patient achieved PASI90. During his follow-up visit at this time, he reported improvements in quality of life. The patient will now consider whether to transition to at-home administration of this current drug regimen.
Clinical Considerations in This Case
1) There are now many biologic options for the management of moderate to severe psoriasis. TNF inhibitors revolutionized the efficacy and safety for the management of severe psoriasis. Use of IL-17 and IL-23 inhibitors further improved the efficacy and safety of these treatments.9-11 There are now multiple biologic agents that have proven efficacy and safety in severe plaque psoriasis without large differences in efficacy to drive treatment choice.9
For example, the 3 currently approved IL-23 inhibitors for plaque psoriasis — tildrakizumab, guselkumab, and risankizumab — have shown broadly similar results with regards to long-term efficacy and safety, although short-term skin clearance may be higher for guselkumab and risankizumab than tildrakizumab.10 This patient may have experienced antibody formation to tildrakizumab, his first-line biologic. Incidence of antidrug antibody response to guselkumab is similar to that of tildrakizumab; however, an antibody response to guselkumab may be less often associated with loss of efficacy.11
Guselkumab, like the other IL-23 inhibitors, has shown high efficacy and an excellent safety profile.12 It is effective both in patients who are biologic-naive and in those who have failed previous biologic treatment. An estimate of guselkumab’s survival rate is 0.8 or above at 52 weeks (ie, 80% of patients treated with guselkumab treatment were still on the drug after 1 year), even in a real-world cohort that included patients who experienced failure of 2 or more previous biologics.13 The survival rates in larger real-life cohorts14 and in a 5-year clinical trial15 were even higher. A common challenge to efficacy of biologic therapy is when a patient is classified as overweight or obese, but the standard guselkumab dose is effective in patients who are underweight or overweight. Patients who are overweight achieved skin clearance or near-clearance with guselkumab more often than with adalimumab.16
Similar to the IL-23 antagonists, IL-17 inhibitors — ixekizumab, secukinumab, and brodalumab — are generally well-tolerated treatments.17 Anti-IL-23 drugs have a lower risk compared with anti-IL-17 drugs for mucocutaneous candidiasis. Anti-IL-17 treatment can, rarely, exacerbate inflammatory bowel disease. This patient’s gastrointestinal symptoms, including baseline frequent diarrhea and abdominal bloating, would have been a reason to choose an anti-IL-23 drug over an anti-IL-17 treatment.
2) Selecting appropriate drug treatment for this patient with severe psoriasis required careful consideration of patient-specific health risk factors. His history of gastrointestinal distress suggested he might not tolerate an IL-17 antagonist or apremilast. In addition, he received medication for depression, which may worsen with apremilast. The desire to avoid exacerbating his depressive symptoms was influential in rejecting apremilast.
This patient was significantly overweight, with a slightly elevated hemoglobin A1c as well as dyslipidemia that was adequately controlled with statin therapy. Any unreported relapses of smoking could further complicate his metabolic risk profile. His heavy alcohol use was another important factor. Alcohol use has increased in the United States population during the COVID-19 pandemic, as occurred in this patient. Both factors presented relative contraindications to methotrexate. This prompted the decision to proceed directly to DMARD therapy.
3) Selection of a specific DMARD was a collaborative physician-patient undertaking. This patient had experienced a prolonged worsening of skin involvement and expressed a preference for a medication that could improve his symptoms relatively quickly. Under these conditions, results with apremilast could have been deemed too slow, fostering disappointment with his treatment. Indeed, 16-week skin clearance results with apremilast tend to lag those of IL-23 inhibitors.10,16 On the other hand, the improvements in quality of life do not exactly mirror the changes in objective disease severity. Drugs that offer lower levels of objective improvement can provide much of the quality of life gains seen with objectively more effective agents. In a complex process of decision making such as this, thoughtful and attentive communication between physician and patient about these competing considerations is necessary to reach an agreement.
Similar conversations were necessary to address the patient’s concerns regarding immunosuppression while receiving DMARD therapy. This concern influenced the choice to overlook TNF inhibitors and IL-17 antagonists as possible therapies, opting instead for drugs in the anti-IL-23 class. Objectively, any above-baseline risk for infection was probably minimal. However, overriding this patient’s concern could have risked his acceptance and adherence to a reasonable treatment plan.
Finally, the issue of medication adherence also influenced treatment selection. Many patients prefer oral administration over injection and would fare better with apremilast than a biologic. But with this patient, such convenience could be a liability, evidenced by his history of medication adherence which could have been worse than he claimed. In study populations, adherence to oral treatment is better than to topical treatment, but worse than adherence to injection treatment.19 Furthermore, apremilast also is associated with gastrointestinal symptoms that may not be tolerable for some patients.20 The effect of irregular dosing of a DMARD is non-negligible for treatment efficacy; this prospect reinforced the decision to reject apremilast.
The same considerations influenced therapy selection among the IL-23 inhibitors. Prescribing tildrakizumab to this patient may have facilitated adherence since it required scheduled visits to his health care facility. In a health care environment where disease management rests on patient-physician collaboration and a sense of therapeutic alliance has the potential to ensure complete medication adherence. It created a sense of accountability of this patient as the administration of each dose was documented in his health record rather than subject to potentially faulty patient recall.
This patient with severe psoriasis initiated a promising course of treatment with biologic drugs. Fortunately, there is now a variety of good choices of medication in these cases. Drug selection required attention to the patient’s multiple comorbid tendencies. Both patient-led and physician-led priorities were considered to develop a treatment plan offering strong likelihood of both objective disease management and patient adherence to the drug regimen.
Steven R. Feldman, MD, PhD, was a consulting dermatologist and skin pathologist for the development of this program. Dr Feldman is a professor of dermatology, pathology, and social sciences and health policy at Wake Forest University School of Medicine in Winston-Salem, North Carolina.
Steven R. Feldman, MD, PhD, reported affiliations with Eli Lilly and Company; GlaxoSmithKline plc; AbbVie Inc.; Alvotech USA Inc.; vTv Therapeutics Inc.; Bristol-Myers Squibb Company; Janssen Pharmaceuticals, Inc.; Samsung Electronics Co., Ltd.; Pfizer Inc.; Boehringer Ingelheim Pharmaceutics, Inc.; Amgen Inc.; Dermavant Sciences, Inc.; Arcutis Biotherapeutics, Inc.; Novartis Pharmaceuticals Corporation; Novan, Inc.; UCB Pharma, Inc; Helsinn Healthcare S.A.; Sun Pharmaceutical Industries Ltd.; Almirall, S.A.; Galderma S.A.; LEO Pharma Inc.; Viatris Inc.; Celgene Corporation, a Bristol-Myers Squibb Company; Ortho Dermatologics, Inc.; VYNE Therapeutics Inc.; Merck & Co., Inc.; Qurient Co., Ltd.; Forté Pharma Laboratories; Biocon Biologics Ltd.; Accordant Health Services, LLC; argenx SE; Sanofi Genzyme; Regeneron Pharmaceuticals, Inc.; National Biological Corporation; CVS Health Corp.; Teladoc Health, Inc.; Eurofins Scientific SE; and Causa Research, Inc.
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Reviewed June 2022