CAD symptoms, daily impacts recorded in new patient assessment

37 patients interviewed to develop CAD-Symptoms and Impact Questionnaire

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Researchers have developed a new patient-reported outcome questionnaire to assess symptoms and the impacts to daily life associated with cold agglutinin disease (CAD).

Called the CAD-Symptoms and Impact Questionnaire (CAD-SIQ), it was developed by analyzing responses from patient interviews. Reactions to cold environments and fatigue were the most commonly reported bothersome symptoms.

CAD-SIQ can be used in clinical practice and observational studies as well as an efficacy measure in interventional clinical trials, said the researchers, who touted the tool as the first of its kind.

“Future research is required to evaluate the responsiveness, validity, and reliability of the CAD-SIQ in both clinical trial and real-world settings,” the researchers wrote in “Development of the Cold Agglutinin Disease Symptoms and Impact Questionnaire (CAD-SIQ),” which was published in the European Journal of Haematology.

CAD is a rare autoimmune disease wherein self-reactive antibodies called cold agglutinins attack red blood cells at cold temperatures, causing symptoms such as fatigue, pain, and shortness of breath that may worsen when it’s cold. Managing the disease means “lifestyle modifications, red blood cell transfusions, and supportive care,” the researchers wrote.

Validated patient-reported outcome (PRO) measures are used in real-world clinical practice and clinical trials for many diseases to understand the patient experience and how it changes with treatment. However, “there is limited knowledge of the patient experience with CAD and its impact on their lives,” the researchers wrote, noting their previous work showed there are no CAD-specific PRO measures that are “appropriate for clinical practice and use in clinical trials or observational studies of patients with CAD.”

Researchers at Sanofi, RTI Health Solutions and in the U.K. sought to learn more about important CAD symptoms and to use that information to develop a disease-specific PRO measure. Sanofi, which markets Enjaymo (sutimlimab-jome), the first and only approved therapy to reduce red blood cell destruction in CAD, funded the study.

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Patient responses about symptoms, their affect on daily life

The researchers interviewed 37 CAD patients (27 women, 10 men) in the U.S. who were recruited from Sanofi’s proprietary CAD Patient Panel. They were mostly white (97.3%) and had a mean age of 67.2. About 40% were employed at the time of the interviews. The first round of interviews included 16 patients (43.2%) and was intended to determine the disease’s main symptoms and their greatest impact.

The most frequently reported symptoms included fatigue (93.8%) and reactions to cold environments (93.8%), such as cold or numb hands/feet, skin discoloration, muscle aches, and headaches, results showed. All said these “were among their most bothersome and/or most important symptoms to treat.”

“I have no energy. I try to get things done and I just end up having to take a nap before I get done with what I wanted to do. I can’t finish chores and things like that,” one patient said.

Other symptoms reported included breathlessness (68.8%), difficulty thinking or concentrating (68.8%), and sleep problems (43.8%).

The patients said their symptoms had substantial impacts on their daily lives, with most (81.3%) reporting they’d given up or limited activities they enjoy. Negative effects on day-to-day activities (75%), physical activities (68.8%), and social life (68.8%) were commonly reported.

More than two-thirds (68.8%) said they had to make lifestyle changes, “such as wearing extra clothing in places where they might be cold, stop working, restricting travel, or changing retirement plans.”

“[CAD] has kept me from doing a lot of the things that I planned to do, or [I] change my plans, and some days, I’m so fatigued that it’ll be 4 o’clock before I realize the day’s gone by because I’m just so tired,” one patient said.

Putting the responses to work

The themes that emerged from the interviews were used to draft a version of the CAD-SIQ that was validated during interviews with the remaining 21 patients.

Researchers used information from this process to tweak the survey prototype to make it as relevant and clear as possible. This yielded a final version of the questionnaire, which covers 11 topics — fatigue, cold sensitivity, dyspnea (breathlessness), wearing extra clothing, limited physical, social and enjoyable activities, difficulty with usual activities, mood, frustration, and anxiety or stress.

“Participants generally found the final 11-item questionnaire to be comprehensive of their experiences with CAD, easy to understand, and simple to answer,” the researchers wrote, noting more work is needed to validate the tool in real-world settings and refine it to make it representative of all CAD patients, regardless of their demographics.

“Furthermore, with additional work including psychometric evaluation, the CAD-SIQ may be suitable for use in clinical trials as an endpoint to better understand patients’ experiences and to support the meaningfulness of changes in other efficacy endpoints,” they wrote, noting the process has resulted in a clearer picture of symptoms that most affect CAD patients.

“CAD was found to negatively impact upon numerous aspects of participants’ daily lives,” the researchers wrote, adding “the insights from our interviews with adults with CAD highlight a need to better understand and quantify the impact of CAD and its treatment on patient quality of life.”