In an interview with PharmaShots, Angela Carroll, US Medical Affairs Scientific Director-Immuno-inflammation at GSK shared her views on a first published article on disease modification in systemic lupus erythematosus, published in Lupus Science & Medicine

Shots:

• The company has published the first research to define disease modification in SLE including LN in the Lupus Science & Medicine. In multiple therapeutic areas, disease modification has become a well-established notion
• In SLE, disease modulation entails reducing disease activity & prevent disease flares, reducing exposure to treatment-associated toxicities, decrease or preventing irreversible organ damage or progression to ESKD. The study will develop personalized treat-to-target therapies for SLE & LN with a focus to prevent organ damage
• SLE patients with extended exposure to OCS are associated with high health resource consumption costs & risk of OCS-related AEs compared to SLE patients who do not use OCS

Tuba: Brief us about the proposed working definition of disease modification in systemic lupus erythematosus (SLE) and lupus nephritis (LN)?  

Angela Carroll: Our proposed framework for disease modification in lupus is guided by the well-established disease modification concept in rheumatology and other therapeutic areas, as well as the currently understood treatment objectives and outcome measures for systemic lupus erythematosus (SLE) and lupus nephritis (LN). Our definition identifies three components of successful disease modification: minimization of disease activity with the fewest treatment-associated toxicities and slowing or preventing irreversible organ damage - or progression to end-stage kidney disease in the case of LN.

Tuba: Can you explain the epidemiology of SLE and LN?

Angela Carroll: At least five million people worldwide have a form of lupus, a chronic autoimmune disease in which the immune system attacks healthy tissues and organs. Kidney damage is a common complication of SLE, and approximately 40 percent of people with SLE will develop lupus nephritis – a type of kidney disease caused by SLE.

Tuba: Can we talk about some of the critical outcome measures of both SLE and LN, especially for patients?

Angela Carroll: Of course. Critical outcome measures in SLE and LN include:

• Control disease activity and prevent disease flares
• Reducing exposure to treatment-associated toxicities, such as corticosteroids
• Improving health-related quality of life measures such as fatigue, pain and depression
• Slow progression of irreversible organ/kidney damage

Tuba: Tell us about the economic analysis associated with SLE flares and organ damage costs.

Angela Carroll: SLE flares represent a significant clinical and economic burden, and healthcare costs increase by 71 percent in patients with SLE-related organ damage. Further, SLE patients with prolonged exposure to oral corticosteroid (OCS) use are associated with significantly higher healthcare costs, health resource utilization costs, and risk of OCS-related adverse events compared with SLE patients with no OCS use.

Tuba: How you think this paper will help people with SLE?  

Angela Carroll: Conceptualizing a framework and criteria for defining disease modification in SLE, this paper marks an important first step in identifying and developing personalized treat-to-target therapeutic strategies for SLE and LN, with a focus on long-term prevention of irreversible organ damage. While disease modification has become a well-established concept in several therapeutic areas, no widely accepted definition of disease modification formerly existed for SLE. As several SLE treatments may fit the disease modification criteria proposed here, the application of the criteria to current treatments is the focus of an ongoing review.

Tuba: What are the benefits of an established definition of disease modification in SLE?

Angela Carroll: Establishing an accepted definition of disease modification in SLE can help clarify which treatments can be considered disease modifiers, offer an opportunity to harmonize clinical trial outcomes and enable comparison between therapies in partnership with a healthcare team to understand how to modify the disease course in the long-term – all of which could ultimately enhance patient outcomes. 

Tuba: Also, tell us something about treat-to-target (T2T) therapies. 

Angela Carroll: The treat-to-target (T2T) therapeutic strategy involves identifying and systematically pursuing appropriate therapeutic targets. Specifically, T2T consists of four key steps: establish a relevant, individualized target – such as remission or low disease activity – take systematic steps to achieve the target, and monitor and adjust the therapy if the target is not achieved. With T2T, treatment objectives include prevention of irreversible organ damage, optimizing health-related quality of life, controlling disease activity, and minimizing co-morbidities and drug toxicity. We’ve seen T2T therapies become increasingly common in treatment plans for other autoimmune diseases, such as rheumatoid arthritis, and are hopeful for similar implementation in lupus treatment in the future.

Source: istock

About Author:

Angela Carroll is the US Medical Affairs Scientific Director-Immuno-inflammation at GSK. She has an extensive background in medical affairs within the systemic lupus erythematosus and lupus nephritis space. She received her master’s degree in Life Sciences at North Carolina State University & Bachelor's Degree in Zoology/Animal Biology from the same University

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