In an interview with PharmaShots, Dr. Philip Mease, MD, Seattle Rheumatology Associates shares insights on the P-III DISCOVER-1 & 2 Studies of Tremfya (guselkumab) for the treatment of psoriatic arthritis in The Lancet Rheumatology

Shots:

• The P-III trials consist of two studies i.e., DISCOVER-1 & 2 evaluates Tremfya in 1100 patients with PsA who have axial symptoms
• The results demonstrated efficacy in the treatment of arthritis, enthesitis, dactylitis, skin disease. The therapy showed an improvement of function, QoL, fatigue & results from the sub-study provide evidence for improvement in the symptoms of spine inflammation & pain        
• Additionally, patients with x-ray or MRI imaging-confirmed sacroiliac inflammation showed an improvement in measures of axial diseases, such as the BASDAI and the ASDAS outcome measures

Tuba: Can you provide a detailed description of the new data on Janssen's Tremfya published in The Lancet Rheumatology? 

Mease: This data was derived from a subset of patients in the Phase 3 trials of TREMFYA in psoriatic arthritis, known as DISCOVER-1 and -2. Over 1100 patients were involved in those two studies. And this sub-study was interested in determining the impact of TREMFYA on symptoms of spine inflammation and pain in patients with psoriatic arthritis, who happen to have the axial component of psoriatic arthritis. We know that approximately 40 to 50% of patients with psoriatic arthritis, depending upon the cohort, will manifest evidence of spine disease that's caused by immunologic inflammation in the spine, which can be progressive and quite disabling. This sub-study was focused on gaining insight as to whether TREMFYA could improve those symptoms. 

What was shown was that patients with x-ray or MRI imaging-confirmed sacroiliac inflammation had significant improvements in validated measures of axial diseases, such as the BASDAI and the ASDAS outcome measures, including specific aspects of the BASDAI such as the spine pain question, and also high thresholds ASDAS responses such as major clinical improvement and inactive disease. 

This data provides support for the use of TREMFYA in patients with psoriatic arthritis who have axial symptoms. This sub-study also provides support for proceeding with a further, and more specific study dedicated to axial PsA, in which formal MRI assessment of sacroiliac joints and spine will be conducted throughout the study to document objective changes in the signs of inflammation in the spine in addition to improvement of clinical symptoms.

Tuba: What is the impact of this data on PsA patients? 

Mease: Because psoriatic arthritis is a heterogeneous disease with multiple clinical domains including arthritis, enthesitis, spine disease, and skin disease, it is valuable to demonstrate improvements in each clinical domain so that patients may have confidence that treatment with TREMFYA will globally improve their disease manifestations. 

Tuba: What are the benefits of Tremfya for PsA patients?

Mease: REMFYA has been demonstrated to improve each of the clinical domains of psoriatic arthritis rapidly and with sustained benefit, allowing patients to achieve target goals of disease remission or low disease activity with consequent significant benefits for function and quality of life. 

Tuba: Discuss the clinical data supporting the efficacy of Tremfya in PsA patients.

Mease: In Phase 3 clinical trials of TREMFYA in PsA, DISCOVER-1, and -2, significant efficacy was shown in the treatment of arthritis, enthesitis, dactylitis, skin disease, improvement of function and quality of life, and improvement of fatigue, all of which significantly impact patients. The data from this sub-study further provides evidence for improvement of the symptoms of spine disease in patients with axial PsA. 

Tuba: What is Guselkumab? How will it change the QoL of patients with PsA with sacroiliitis?

Mease: Guselkumab (TREMFYA) is a p19 interleukin (IL-)23 inhibitor, which binds to and inhibits an important pro-inflammatory cytokine that is part of the pathogenesis of conditions such as psoriatic arthritis, psoriasis, and inflammatory bowel disease.

In trials such as the DISCOVER-1 and -2 trials, it has been demonstrated that disease improvements lead to significant and measurable improvements in quality of life. We know that manifestations of spine disease such as sacroiliitis are an important part of the disease, and therefore a part of the global improvement that leads to the betterment of the quality of life. 

Tuba: How does Tremfya plan to compete with other products in PsA space, such as Cosentyx and Adalimumab among others?

Mease: Patients with psoriatic arthritis may not adequately respond to the various treatments that have been approved, such as the IL-17 inhibitors or the TNF inhibitors, or the patient may have a good effect but then lose effect over time. Or they may have issues with safety or tolerability. Thus, it is important to have multiple medications and mechanisms of action to effectively treat all patients with PsA over time. Further, it is valuable to have medications such as TREMFYA, with an excellent safety profile as well as efficacy profile, for patients to choose. 

Tuba: What are the biggest challenges you have faced in developing the treatment for this disease?

Mease: A clinical trial program for approval of a drug in the treatment of psoriatic arthritis requires numerous patients enrolled across the world to reliably demonstrate efficacy and safety. We are grateful that not only companies, but also numerous medical investigators and patients are willing to invest the resources, time, and energy that it takes to accomplish these substantial clinical trials.

Image Source: National Heart, Lung & Blood Institute

About Author: 

Philip Mease is the Director of Rheumatology Research at the Swedish Medical Center/Providence St. Joseph Health and Clinical Professor at the University of Washington School of Medicine. He received his undergraduate and medical degrees at Stanford University Medical School and completed his residency in internal medicine at the University of Washington's School of Medicine

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