Compliance of Rucotinib in the treatment of MF patients: an interim analysis of an Italian prospective real world study (ROMEI)

Myelofibrosis (MF) is a progressive myeloproliferative tumor with a short median survival time of only 5.
7 years, high-risk patients only 2.
3 years, and about half of the patients died due to disease progression [1]
.

Rucotinib is an oral highly selective JAK1/2 inhibitor.
It has a significant effect on improving splenomegaly and constitutional symptoms in MF patients.
It can also delay or reverse myelofibrosis and bring survival benefits to MF patients.
[2]
.

The United States and China approved the marketing of rucotinib in 2011 and 2017 respectively, breaking through the treatment of MF patients [3]
.

However, rucotinib is usually self-administered at home, and the patient's compliance and the effect of compliance on treatment are not yet known
.

Recently, the results of the interim analysis of the prospective cohort study ROMEI, which explores the compliance of MF patients receiving rucotinib treatment in Italy, were published online.
This article provides a detailed interpretation of the literature in order to improve clinicians' compliance with rucotinib treatment.
Pay attention to [4]
.

Methods A prospective cohort study.
The Morisky Medication Compliance Scale Assessment Medication Compliance Study was conducted in 42 academic and community centers in Italy, and included MF patients who were 18 years of age and had not been treated with Rucotinib before enrollment
.

The Morisky Medication Compliance Scale (MMAS-8) was used to evaluate the average change in patient compliance over time from the 4th week, as well as the proportion of patients with different compliance among all eligible patients and patients who completed the questionnaire
.

Table 1 MMAS-8 questionnaire results: One third of MF patients have poor compliance with rucotinib, which may affect the treatment results of patients 1.
More than one third of MF patients have poor compliance with rucotinib treatment for the general population (N=188) analysis showed that 87%, 83%, 78%, and 71% of patients completed the MMAS-8 questionnaire at 4, 8, 12, and 24 weeks, respectively
.

From week 4 to week 24, the average MMAS-8 total score remained stable (Table 2)
.

At each visit, the proportion of patients with low, moderate, and high compliance remained stable.
60-75% of patients had high compliance, and 25-40% of MF patients had poor compliance with rucotinib treatment (Table 2)
.

Table 2 Average total MMAS-8 score and compliance category Note: High compliance, MMAS-8 total score 8; Moderate compliance, MMAS-8 total score 6-8; Low compliance, MMAS-8 total score <6; Poor compliance, MMAS-8 total score <8
.

SD: standard deviation; MMAS-8: 8-item Morisky Drug Compliance Scale
.

a Based on the overall population and the percentage of complete completers, respectively
.

bBased on the percentage of all patients (in the overall population or complete completers) who completed the questionnaire at this visit
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The results of the analysis of the subgroup of complete questionnaires were consistent with the total population.
From the 4th week to the 24th week, the average MMAS-8 total score remained stable (Table 2)
.

64-74% of patients have high compliance, and 26-36% of patients have poor compliance (Table 2)
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Taken together, one-third of MF patients treated with rucotinib have poor compliance, and these patients may undermine disease control due to inadequate treatment
.

2.
Both high and low compliance behaviors remain stable during long-term treatment, which may be driven by the patient's internal factors.
Based on the analysis of the complete population, 78% of patients with high compliance in the 4th week are in the 8th week.
High compliance is still reported
.

Among patients with moderate compliance at week 4, 50% turned to high compliance at week 8, and 50% reported poor compliance
.

Among patients with low compliance in the 4th week, 67% still reported poor compliance
.

From week 4 to week 12 and week 24, the changes in compliance category were similar
.

It can be seen that the high and low compliance behaviors remain stable during long-term treatment, which may be driven by internal patient factors
.

Figure 1 The distribution of the compliance categories over time among the complete completers (n=101) based on the compliance category analysis in the 4th week.
Note: The compliance categories in the 4th week are dark gray (high compliance) and medium gray ( Moderate compliance) and light gray (low compliance) indicate 3.
The changes in compliance are mainly related to unintentional behaviors.
During the 6-month follow-up, 46% of patients who completed the full compliance category maintained the same compliance category, while 54% Of patients’ compliance category changed at least once between the subsequent two follow-ups, that is, compliance is unstable (Figure 2)
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Among patients with stable compliance, 42% consistently reported high compliance (Figure 2)
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Among the 55 patients with unstable compliance, most patients had 1 improvement and/or deterioration in compliance between the 4th and 24th weeks (Table 3), and most of the improvement or deterioration in compliance was due to The patient's unconscious behavior
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Figure 2 The distribution of overall compliance categories during the 24-week follow-up period of fully completed persons (n=101) Note: Unstable compliance is defined as a change in compliance at least once between the subsequent two follow-ups.
Table 3 Unstable compliance Intentional and unintentional changes in scores of completed participants (n=55) 4.
No correlations were found between the compliance category and the patient's spleen, MPN10 symptom response, and the incidence of hematological adverse events.
An exploratory analysis of the correlation between the incidence of adverse events did not find a correlation between compliance and the incidence of splenic reactions or hematological adverse events, and patients with high compliance were more likely to obtain symptomatic responses than patients with poor compliance
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However, due to the limited number of patients, the results must be interpreted with caution
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Conclusion One-third of MF patients have poor compliance with rocotinib treatment and may not be adequately treated.
During the 6-month follow-up period, the average total MMAS-8 score remained stable in the overall population and complete completers
.

The rates of patients with poor compliance are 25–40% and 26–36%, respectively.
That is, one third of patients treated with rucotinib may not be adequately treated due to poor compliance, which may undermine disease control
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In order to fully understand and improve drug compliance and clinical results, efforts should be made to incorporate standardized compliance assessments, such as MMAS-8, into future clinical trials and daily clinical practice, and to formulate corresponding interventions to address these patients.
The problem of poor compliance
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Conclusion In the process of rucotinib treatment of MF, in addition to symptom monitoring such as symptom questionnaire and spleen size measurement, treatment compliance should also be reviewed regularly [4]
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In the case of poor response, poor disease control caused by treatment intolerance, treatment failure, and poor compliance should be accurately distinguished [4]
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This study is the first to evaluate the compliance of rucotinib in MF patients based on the MMAS-8 questionnaire
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Analysis results show that at least one third of MF patients have poor compliance with rucotinib treatment, and may not be adequately treated due to non-adherence.
In real clinical practice, this proportion may be underestimated by clinicians
.

Considering the clinical consequences and related costs of poor adherence to treatment, these data indicate that further research is needed to increase our understanding of the behavior behind poor adherence and to develop effective interventions to address this problem
.

References: [1] Cervantes F, Dupriez B, Pereira A, et al.
New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment-ScienceDirect[J].
Blood, 2009,113 (13):2895-2901.
[2] Verstovsek S, Gotlib J, Mesa RA, et al.
Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses[J].
Journal of Hematology & Oncology, 2017, 10(1):156.
[3] https://db.
yaozh.
com/instruct/14985.
html.
[4] Guglielmelli P, Palandri F, Selleri C, et al.
Adherence to Ruxolitinib, an Oral JAK1/2 Inhibitor, in Patients With Myelofibrosis: Interim Analysis From an Italian, Prospective Cohort Study (ROMEI)[J].
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