SRUK funding is playing a key role in improving how we determine the success of new treatments in clinical trials. These projects aim to better inform researchers of the impact of potential therapies, ultimately improving wellbeing and quality of life for people living with scleroderma.

The COVID-19 pandemic has improved public knowledge of the clinical trials process that is necessary for the approval of new drugs. Within such trials, outcome measures and endpoints are fundamental for study design and in showing that the treatment is effective.

‘Outcome measures’ are measurable, clinical changes in a patient occurring as a result of treatment. For example, the modified Rodnan Skin Score (mRSS) to measure skin thickness is commonly used within trials for scleroderma. An ‘endpoint’ is the measured change seen in a chosen outcome measure at a specific point in time e.g., the difference between pre-treatment and post-treatment mRSS. This is essentially a snapshot of what is happening in the skin, although it may not always capture the full impact of a drug, since there could potentially be other benefits that are not obvious using mRSS. Consequently, there is now a focus on combining outcome measures to give a single endpoint. Two SRUK and World Scleroderma Foundation-funded projects are working on this, CRISS and CRISTAL – that are specifically designed according to the two main types of this condition. Our recent research piece ‘What’s the outcome? Measuring the effectiveness of new treatments in clinical trials’ Introduced these two projects, and additional information can also be found here.

The CRISS Index in dcSSc

Diffuse cutaneous systemic sclerosis (dcSSc) usually affects the skin and in some cases the internal organs, leading to heart, lung and kidney complications. In 2016 an index designed to evaluate treatments for dcSSc was developed, named CRISS (Combined Response Index in SSc). CRISS has demonstrated its success in reflecting how patients feel and function, furthering treatment options by facilitating phases two and three in clinical trials. 

The CRISTAL Index in lcSSc

Limited cutaneous systemic sclerosis (lcSSc) affects smaller areas of skin and sometimes the gastro-intestinal tract. Between 2000 and 2018, only four out of 97 scleroderma trials focused specifically on lcSSc, reducing opportunities for new treatments. This underrepresentation is probably due to the paucity of outcome measures for lcSSc, since lesser skin involvement compared to dcSSc shows fewer dramatic changes in mRSS.

Dr Dinesh Khanna at the University of Michigan is therefore developing the ‘Combined Response Index for Scleroderma Trials Assessing Limited SSc’ (CRISTAL). This aims to achieve a similar impact within lcSSC as CRISS achieved for dcSSc. Patients are central to this exciting project, which will review known lcSSc-specific outcome measurers and its array of clinical symptoms. In addition to consulting with other clinical experts, patients will provide insight into their symptoms and the impact upon quality of life. This input will deliver the final index which it is anticipated will be validated in a clinical setting.

A composite index for lcSSc is essential to ensure new treatments are relevant to this neglected subgroup, and patients are not missing out on developing treatments. We hope that CRISTAL will help bring greater clarity to clinical trials in lcSSc.