Cold Agglutinin Disease (CAD) Can have SERIOUS consequences

Patients may be at risk for dangerous events1

Severe anemia events are unpredictable1

of patients had at least 1 severe anemia event within the first year of follow‑up

Data from a retrospective review of a healthcare system database in patients with CAD (n=29) who were included based on hemoglobin readings and follow-up.

of patients had a severe anemia event within first 6 months of pharmacotherapy

Data collected from 18 patients with at least 6 months of follow-up after initial therapy in a retrospective review of a healthcare database.

Study limitations

  • The database did not record reasons for loss to follow-up. Some patients with severe anemia at disease onset could not be followed for a year or more
  • Given that the database captured data from the Stanford clinics, this study captured the minimum levels of care for this cohort of patients with CAD

CAD was associated with an elevated thromboembolic threat2

In a sensitivity analysis of a retrospective claims-database study of patients with CAD (n=425) vs a matched cohort* (n=4126), there was a:

Comparison of  Thromboembolic Events in CAD patients vs non-CAD patients

Thromboembolic risk increased from time of identification and throughout the study2

Cumulative incidence curve of first TE after index date in patients with and without CAD demonstrated significant differences in the development of TEs over time (P<0.0001)

Graph Showing Time to first Thromboembolic Event in patients with CAD vs non-CAD patients

The date of first mention of CAD for patients with disease.

With 95% confidence limits, Gray’s test P<0.0001.

  • The increased risk of TEs in patients with CAD was noted from the time of identification through the entire 10-year follow-up period
  • The adjusted absolute risk difference calculation revealed a significant excess risk of TEs for patients with CAD vs patients without CAD at 1 year (11.9 per 100 patients; 95% CI: 11.7-12.1 per 100 patients) and 5 years (11.9 per 100 patients; 95% CI: 11.6-12.2 per 100 patients) after the index date

Study limitations

  • Claims-based data and TE diagnostic codes (ICD-9 and ICD-10) may be subject to coding errors
  • Lack of data on specific CAD treatments in relation to TE development
  • Patients with both CAD and CAS were likely included in the main analysis,* as the database did not allow for differentiation
  • Lack of data on hereditary and acquired thrombotic risks which may also contribute to the occurrence and severity of these events
  • Only the first TE of each type was included, so the risk of TEs may have been underestimated
  • There may be some selection bias, as patients with <1 year of time in the Optum system prior to the index date were not included. This may have excluded the most severely affected patients due to early death

*Data used a Cox regression model adjusted for age, sex, race, region, active time in the system, history of prior TEs, history of HIV/AIDS, history of malignant cancer except for nonmelanoma skin cancer, history of organ failure or transplantation, history of chemotherapy use, history of radiation use, history of anticoagulant medication use, history of antiplatelet medication use, and CCI score.

Additional studies are needed to further understand the risks associated with CAD

Despite current management strategies, patients still require healthcare resources3,4

A retrospective claims-database study of patients with CAD/CAS (n=410) measuring healthcare resource utilization vs a general population cohort (n=3390) found that, within 1 year after diagnosis:

Icon representing hospital inpatient services
2.5X more patients with CAD used hospital inpatient services compared with matched comparisons: 36.3% (n=149) vs 14.5% (n=491); (P<0.0001)
Icon representing outpatient visits
17.3 visits: the average number of outpatient visits compared with 6.7 visits for matched comparisons (P<0.0001)
Icon representing emergency room visits
1.5X more patients with CAD required emergency room visits compared with matched comparisons: 25.9% (n=106) vs 17.2% (n=583); (P=0.0005)

Study limitations

  • Patient data utilized from the Optum-Humedica database did not explicitly differentiate between patients with primary and secondary CAD for this data
  • Patients were only selected from the Optum-Humedica data set, which is limited to commercially insured patients and may not represent the overall CAD population
  • Patients with CAD were identified using clinical notes, not diagnostic codes or laboratory results

CAD and general population cohorts were matched on CCI score, sex, ethnicity, region, follow-up, age, and entry date.

Sponsored by Bioverativ Therapeutics Inc., a Sanofi company.

A retrospective claims-database study of patients in Denmark with CAD (n=85) measuring healthcare resource utilization vs matched comparisons* (n=826) found that, within 1 year after diagnosis:

Icon representing emergency room visits
2.5X more patients with CAD used hospital inpatient services compared with matched comparisons: 53% (n=45) vs 21% (n=176); (P<0.0001)
Icon representing outpatient visits
2X more patients with CAD used hospital outpatient services compared with matched comparisons: 94% (n=80) vs 56% (n=459); (P<0.0001)
Icon representing hospital inpatient services
2X more patients with CAD used emergency services compared with matched comparisons: 20% (n=17) vs 12% (n=101)

Study limitations

  • Registry data allow for complete universe of patients within Denmark
  • Claims‐based identification of patients with CAD and utilization measures may, however, be imprecise and coding errors are possible

*Patients with CAD were matched without replacement 10:1 with comparison patients from the general population based on age (±3 years), sex, and CCI categories.

Hear from Brad,

a patient living with CAD, as he discusses its impact on his life.

When they said I was primary CAD, cold agglutinin, my first reaction is, “Okay, what is it?” and second reaction is “Well, let’s fix it,” and unfortunately the doctors all say exactly the same thing, “There’s nothing we can do for you, there’s no cure for it,” and it’s very cavalier the way they say, “Don’t get cold.” “Don’t get cold” is a very easy thing for people to say, and it’s easy for people to deal with, but when you have this disease it’s not so easy to deal with because cold can happen at any point in time. Coming out of the shower, just that temperature change from your body being wet to a cooler environment can trigger problems, right? Going in a heated swimming pool, the heated swimming pool is fine, that’s something you can deal with. It’s coming out of the swimming pool that is where the change, that temperature change, and it is that minor of a change, right? There’s a lot of precautions that we now have to take in our lives, which changed our lives. It changes all the time, right? That’s the whole thing with it is we may be used to something this year, next year there’s probably going to be something different. This is a journey that is uncertain and is always uncertain, and it never, it never really nails itself down because it changes all the time, right? So psychologically, you have high days and you have low days, and absolutely I went through depression and anger and the whole gamut of emotions for it. Now I’ve gotten to the point and I’m at a good point in my life where I’ve accepted it now, and now it’s just my day-to-day changes and it’s just you adapt to that, but psychologically it’s hard to deal with because most people will look at you and say, “Well, you look fine. You look fine,” and when people say that, it’s “Well, yeah, I look fine but inside I’m not; it’s the inside part that is not working properly.” And that’s part of the battle, too, is because everybody that you meet says, “Well, you don’t look sick.” Well, I don’t look sick because I try and keep myself healthy and all the rest, right? But yeah, it’s a hard journey and I’m not going to deny that it’s not but, like I said, to me, this is probably one of the hardest things I’ve ever done in my life–is to deal with this day-to-day.

Icon of blood representing CAD symptom of hemolytic anemia

The complement
pathway plays a
critical role in CAD

Icon of checklist

Understand criteria
to diagnose CAD
in patients

aHR=adjusted hazard ratio; CAD=Cold Agglutinin Disease; CAS=cold agglutinin syndrome; CCI=Charlson Comorbidity Index; ICD=International Classification of Diseases; TE=thromboembolic event.
References: 1. Mullins M, Jiang X, Bylsma LC, et al. Cold agglutinin disease burden: a longitudinal analysis of anemia, medications, transfusions, and health care utilization. Blood Adv. 2017;1(13):839-848. doi:10.1182/bloodadvances.2017004390 2. Broome CM, Cunningham JM, Mullins M, et al. Increased risk of thrombotic events in cold agglutinin disease: a 10‐year retrospective analysis. Res Pract Thromb Haemost. 2020;4(4):628-635. doi:10.1002/rth2.12333 3. Su J, Bylsma LC, Jiang X, Morales Arias J, Jain N, Nordyke RJ. Healthcare resource utilization among commercially insured patients with cold agglutinin disease in the United States. J Med Econ. 2020;23(8):902-907. doi:10.1080/13696998.2020.1764006 4. Vago E, Nicholson G, Horvath-Puho E, et al. Healthcare resource utilization (HRU) among patients with cold agglutinin disease (CAD) in Denmark. Poster presented at: ISPOR Europe 2020; November 16-19, 2020; Virtual conference. Poster PRO43.