Kavita Darji

Review of phase III trial data on IL-23 inhibitors tildrakizumab and guselkumab for psoriasis

The development of monoclonal antibodies targeting IL‐12 and IL‐23 has enhanced the therapeutic options available for psoriasis patients. Recent research suggests that IL‐23 alone plays a role in the pathogenesis of psoriasis. The objective was to review the phase III clinical trial data for the anti‐IL‐23 agents to evaluate the safety and efficacy profile of each agent. We reviewed the results of the phase III clinical trials for the anti‐IL‐23 agents tildrakizumab and guselkumab. The results of phase III trials on risankizumab have not yet been reported. By week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was >60% among the most efficacious dose of each agent. The percentage of patients achieving PASI 90 at week 16 was the primary endpoint for the phase III trials for guselkumab, which was above 70%. The safety profiles of the agents were comparable, with the most commonly reported adverse events of nasopharyngitis and upper respiratory tract infections. The anti‐IL‐23 agents demonstrated a rapid clinical improvement that is similar or superior to the improvement seen with currently marketed IL‐17 inhibitors with a favourable short‐term safety profile. The results of the phase III trials support the notion that IL‐23 is a potential target in psoriasis treatment.

Review of IL-17 inhibitors for psoriasis

Abstract Background: The development of biologic agents directed against distinct cytokines and receptors has advanced the therapeutic options available for psoriasis patients. Evidence from preclinical studies suggests that IL-17 may contribute to the pathogenesis of psoriasis. Objective: The objective was to review the safety and efficacy profile for each IL-17 inhibitor by evaluating phase III clinical trial data. Methods: We reviewed the results of phase III clinical trials for the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab. Results: At week 12, the proportion of patients reaching Psoriasis Area and Severity Index (PASI 75) was above 60% for the most efficacious dose of each agent with favorable and comparable safety profiles. The most commonly reported adverse events were nasopharyngitis, headache, and upper respiratory tract infection. Conclusions: The clinical improvement among psoriasis patients on IL-17 inhibitors is similar or superior to the improvement seen with commercially produced biologic agents available accompanied by a favorable short-term safety profile. The results of the phase III trials indicate that IL-17 inhibitors are effective therapeutic options for psoriasis patients.

Interpreting Clinical Trial Data

Effective interpretation of clinical trial data allows for the integration of high-quality clinical research into clinical practice. Evidence from clinical trials directly impacts clinical decision making, which ultimately guides patient management (Page, Int J Sports Phys Ther 9: 726, 2014). The purpose of this chapter is to provide an overview of fundamental aspects of clinical trials, such as study designs, analyses, and methods of handling missing data along with potential sources of bias and uncertainty. Subject withdrawal can make statistical analysis difficult as studies are aimed to determine the impact of an intervention from beginning to end. The different approaches to account for missing data are presented: last observation carried forward (LOCF), nonresponder imputation (NRI), as-observed data analysis, and anytime analysis (Langley and Reich, Br J Dermatol 169:1198–1206, 2013). Identifying sources of error and understanding limitations of these methods helps clinicians evaluate the validity of clinical data, ultimately enhancing clinical decision making and patient care.

Severely Obese 42-Year-Old with Psoriasis

Psoriasis is associated with a range of diseases, including obesity. Debate exists regarding which of these two conditions comes first. In patients who weigh more, first-line biological drug choices include infliximab and ustekinumab because they are weight based. On the other hand, systemic treatments can often cause adverse effects and metabolic derangements in these patients.

41-Year-Old with Nail Deformities

Nail disorders, commonly seen as pitting and deformation, are common manifestations in psoriasis patients. Topical therapies are the first-line treatment for mild cases of nail deformities in psoriasis patients. Intralesional corticosteroids have been shown to be beneficial for limited nail psoriasis. Systemic therapies are most commonly used if nail psoriasis presents in a patient with moderate-to-severe plaque psoriasis or psoriatic arthritis.

69-Year-Old with Psoriasis and a History of Skin Cancer

A 69-year-old female with a long history of psoriasis presented to the clinic for follow-up after undergoing electrodesiccation and curettage of nonmetastatic squamous cell carcinoma on the left knee. Her psoriasis and psoriatic arthritis have been managed with methotrexate for the past 5 months. She has no prior history of cancer, but multiple actinic keratoses and squamous cell carcinoma have been noted in previous visits. Two previous squamous cell carcinomas were found on the left forearm and left lateral shin and treated similarly with electrodesiccation and curettage. Follow-up visits have not shown signs of recurrence. The patient denies a history of smoking, exposure to radiation, and use of other immunosuppressant medications. She does admit to excessive ultraviolet light exposure and minimal use of sunscreen. The patient has a family history of psoriasis. However, she denies a family history of cancer, including skin cancer.

Tuberculosis Infection in a 58-Year-Old with Psoriasis

A 58-year-old male with a 10-year history of psoriasis presented to the clinic for worsening of psoriasis after a month-long hospital admission for a military tuberculosis infection. The patient received antituberculous medications during his admission and was advised to continue the regimen for an additional 8 months. At that time, his psoriasis medication, adalimumab, was immediately discontinued. Subsequently, his psoriasis worsened, affecting a significant proportion of his body. The patient was previously using adalimumab for 3 years with considerable benefit. Of note, before starting adalimumab, the patient tested positive for latent tuberculosis and was prescribed isoniazid. However, it was unclear if the patient was compliant with his medication. The patient denied fever, chills, and night sweats. However, he continued to experience fatigue and poor weight gain. He did not have any other medical conditions.

Infected Joint Prosthesis in a 56-Year-Old with Psoriasis

A 56-year-old female with an extensive history of psoriasis, psoriatic arthritis, and systemic lupus erythematosus presented for evaluation of worsening psoriasis after discontinuing adalimumab. Her adalimumab was stopped 6 weeks earlier when an infected right elbow prosthesis was discovered. The patient’s surgeon planned to reassess her after completing an extended intravenous antibiotic regimen to determine if further intervention would be necessary. Since stopping adalimumab, she noticed worsening of her psoriasis on her face, scalp, and both upper and lower extremities. The patient had used adalimumab for the past 5 years with good results, marginal side effects, and no prior serious infections. She was otherwise healthy and denied fever, chills, and night sweats.

50-Year-Old with Psoriasis and Hepatitis B Virus Infection

A 50-year-old female with a 14-year history of psoriasis presented for follow-up after consultation for systemic psoriasis therapies. Previous treatments with ultraviolet phototherapy and topical medications were marginally effective. Before initiating adalimumab, routine screening revealed mildly elevated AST and positive serological markers indicative of chronic hepatitis B infection. The patient denied prior knowledge of infection. She was otherwise healthy and did not complain of fatigue, poor appetite, nausea, abdominal pain, dark urine, light stool color, or fever. The patient has a family history of psoriasis.

Joint Stiffness in a 45-Year-Old with Psoriasis

A 45-year-old male with a 27-year history of psoriasis and psoriatic arthritis was referred for evaluation of worsening psoriasis and joint stiffness. Etanercept and methotrexate provided moderate relief of his symptoms; however, lately the patient experienced “flares” in both wrist and finger joints. These episodes occurred about once a month and caused significant swelling and stiffness in his joints that last for approximately 3 days. He stated that stiffness and pain are worse in the mornings and moderately improved with activity or nonsteroidal anti-inflammatory drugs. The patient denied fever, recent illness, physical trauma, muscle weakness, and tingling or numbness in the extremities. He denied a family history of psoriasis or psoriatic arthritis.