Nationwide estimation of the number of patients receiving MTT
As of 2019, the MDV database covered 22% of acute-phase medical institutions in the DPC system in Japan. Provided that all cancer patients are seen at acute-phase medical institutions, we estimate that approximately 870,000 cancer patients were treated with MTT during the follow-up period in this study (the number of patients included as the source cohort [190,536] divided by 0.22). The Ministry of Health, Labour, and Welfare in Japan estimated that as of 2017, there were 1,782,000 cancer patients. Considering that most anti-cancer drugs developed since 2000 are MTTs, “patients treated with MTT” who were included in our study cohort are expected to account for a large proportion of cancer patients.
Moisturizer utilization pattern
The proportion of patients prescribed moisturizers was 35.7% among patients prescribed MTT during the study period. The proportion varied greatly among the MTT groups. The proportion of moisturizer users was the highest in the EGFR inhibitor group (71.4%) followed by the multikinase inhibitor group (50.2%), immune check point inhibitor group (42.1%), and the VEGF inhibitor group (40.2%). The proportion of users was low in the anti-CD20 antibody group (23.2%) and the BCR-ABL inhibitor group (15.4%). The proportion of moisturizer users over time showed an increasing trend (31.6% in 2011 to 39.1% in 2018), and the proportion of moisturizer users in the EGFR inhibitor group increased from 53.5–74.7% during the same period. Moreover, in the 2018 data, the proportion of moisturizer users in the BCR-ABL inhibitor group, which was the lowest among the MTT groups, reached 21.1%. These findings suggest that moisturizer use has become common not only when EGFR inhibitors are used, which commonly cause skin disorders because of their mechanisms of action and for other reasons, but also when other anti-cancer drugs are used. The proportion of EGFR inhibitors among the MTT groups actually decreased (13.8% in 2012 to 5.8% in 2018), which suggests that the increasing trend in moisturizer use was not caused by changes in the type of MTT being prescribed.
Variations in the moisturizer utilization pattern
In Group M, 31.5% of the patients were prescribed moisturizers within 1 month after beginning MTT. However, the start of prescriptions was not limited to a certain period. Frequent symptoms of skin disorder differ depending on the MTT. Symptoms such as acneiform rash peaked approximately 2 weeks after beginning MTT, while other symptoms, such as xerosis and paronychia, mainly developed after 28 days or later [10, 11]. These findings suggest that variable timing of initiating moisturizer use in the present analysis reflects variable timing in the onset of skin disorders.
Overall budget impact of moisturizers
When drugs were compared according to their unit prices, there was a large difference between moisturizers and MTTs. Therefore, when we evaluated medical costs and drug costs per patient, the contribution of moisturizer costs was small. Specifically, the analysis of total medical costs at 6 months and 12 months showed that the difference in medical costs between Group M and Group N was 0.467 million yen at 6 months and 1.029 million yen at 12 months. However, the difference in moisturizer costs was 4008 yen at 6 months and 6033 yen at 12 months, which accounted for 0.1% of the total medical costs and only 0.6% in the difference in the total costs at 12 months.
The total medical costs for users of anti-cancer drugs in Japan, calculated by dividing the total medical costs of users of anti-cancer drugs in the MDV database by 22%, which is the patient coverage of this database, was 1.96 trillion yen (1.17 trillion yen for non-users of moisturizers and 0.87 trillion yen for users); moisturizer costs accounted for 760 million yen. Therefore, conceivably, the medical costs of prescribed moisturizers in cancer treatment is extremely low. The main factors causing the high medical costs in Group M were extended hospitalization and increased costs of drugs other than moisturizers.
The present study used commercially available claims data from DPC hospitals and did not capture treatments performed in non-DPC hospitals or clinics. Follow-up of patients who were transferred to other medical institutions during treatment was also not possible. In Japan, unlike in other countries, the availability of a health insurance claims database at the national level is extremely limited. However, some drug utilization studies using commercially available claims data have been reported despite the limitations [12, 13, 14]. We expect that similar analyses will be performed in the future using a broader database, to improve the generalizability of the findings in this study, if such a database becomes available.
The present study was not a comprehensive analysis of cancer treatment. We analyzed only cancer patients who were prescribed MTT. Some MTTs, for example, EGFR inhibitors, are expected to cause skin disorders frequently because of their mechanisms of action. Therefore, the need for moisturizers in patients receiving MTT are higher than for patients receiving other anti-cancer drugs, which was why patients receiving MTT were chosen as the first cohort. However, because cytotoxic anti-cancer drugs can also cause skin disorders as an adverse event, broader studies analyzing patients receiving a wide variety of anti-cancer drugs is desirable.
When we selected the patients for this study cohort from the source cohort, we excluded patients who were prescribed moisturizers before initiating MTT. This criterion was set to exclude the use of moisturizers to treat skin disorders not caused by anti-cancer drugs. However, this criterion also excluded patients prescribed moisturizers prophylactically and those who were already being treated with other anti-cancer drugs and who were prescribed moisturizers for skin disorders. Because of the stricter inclusion/exclusion criteria we set to identify only patients strongly associated with skin disorders caused by MTT, we expect that the number of patients using moisturizers in clinical practice is higher.