Preferred S-adenosylmethionine prescription in routine practice for intrahepatic cholestasis management: results of a multinomial logistic regression grid-optimization approach

Figures & data

Table 1 Example categorization of patients following AdoMet treatment

Preference probability margins	Sample patient 1 preferences 400 mg injection, 50% 800 mg injection, 15% 800 mg tablet, 35%	Sample patient 2 preferences 400 mg injection, 50% 800 mg injection, 45% 800 mg tablet, 15%
a = 20%, b = 10%	Category V	Category VI
a = 20%, b = 20%	Category VII	Category VI
a = 10%, b = 20%	Category I	Category VI

Notes: a = minimal distance between highest preference probability and the two other preference probabilities; b = distance between the lowest preference probability (of three) and the two other preference probabilities.

Table 2 Patient demographics and baseline characteristics

Parameters	All patients (N = 401)
Patient characteristics
Gender, n (%)
Male	236 (58.9)
Female	165 (41.1)
Mean age, years (SD)	47.9 (12.4)
Mean weight, kg (SD)	79.3 (15.9)
Race, n (%)
White	395 (98.5)
Black	0 (0.0)
Asian	2 (0.5)
Others	4 (1.0)
Distribution of patients depending on the cause of IHC^a
Liver diseases, n (%)
Hepatitis	304 (75.8)
Liver cirrhosis	100 (24.9)
Steatosis	76 (19.0)
Cholangitis	31 (7.7)
Other liver diseases	19 (4.7)
Non-liver disease, n (%)
Congestive heart failure	9 (2.2)
Others	3 (0.7)

Note: ªOne patient could have more than one cause of IHC.

Abbreviations: IHC, intrahepatic cholestasis; SD, standard deviation.

Table 3 Clinical indicators in the stepwise multinomial logistic regression selection model

Nature of measurement	Clinical indicator	Value used in MLR grid-optimization model
Laboratory test	Total bilirubin, aspartate aminotransferase, platelet count, total cholesterol	Laboratory values
Symptoms	Jaundice, pruritus, dyspepsia, fatigue, appetite, sleep, pain, malaise, weakness, mobility, ability to perform usual activities, irritability, anxiety, difficulties with concentration	Number of these symptoms
Indication	CPC Steatosis	1 = indicated category 0 = category not indicated −1 = “unknown” 0 = not present 1 = present
Ultrasound	Intrahepatic bile duct dilation Increased liver size	1 = no 2 = yes 1 = no
Resource	Hospital admission in the previous 2 months before the start of treatment	1 = yes 0 = no

Notes: The preference (probability) for the 400 mg versus 800 mg injection (reference) was calculated as follows (clinical indicators are ordered by p-value from low to high; dark grey highlight: P<0.01; light grey highlight: P=0.01-0.05; others: P>0.05): Logit(preference probability 400mg injection vs 800mg injection)= -1.89 -1.15*In (total bilirubin) -1.96* CPC (A) -0.84* CPC (B) +1.97* CPC (C) -1.41* steatosis +1.64* intrahepatic bile duct dilation -1.06* hospital days ‘yes’ in 2 months before start of treatment -0.46*ln(AST) + 1.57*ln(total cholesterol) + 1.29*ln(platelet count) -0.088 *number of symptoms -0.44* liver size increased. For the 800 mg tablets versus 800 mg injection (reference) the following equation as obtained: Logit(preference probability 800mg tablets vs 800mg injection)= 11.31 -0.39* number of symptoms -0.82*ln(AST) + 2.49* In (total cholesterol) -1.78* steatosis -1.42* liver size increased -0.67*ln(platelet count) -0.25* CPC (A) -0.20* CPC (B) + 0.56 * CPC (C) -0.29* hospital days ‘yes’ in 2 months before start of treatment -0.18 *ln(total bilirubin) -0.29 *intrahepatic bile duct dilation.

Abbreviations: AST, aspartate transaminase; CPC, Child–Pugh classification; MLR, multinomial logistic regression.

Figure 1 (A) AdoMet treatment prescription versus total bilirubin; (B) AdoMet treatment prescription versus number of symptoms; and (C) AdoMet treatment prescription versus Child–Pugh classification.

Figure 2 Distribution of patients (N) across categories (I–VII) following the calculated allocation model based on statistical significance and grid-optimization.

Notes: The number of actual prescriptions is provided for each of the categories I–VII as N = (n₁, n₂, n₃), where n₁= number of patients to whom the 400 mg injection was prescribed, n₂ = number of patients to whom the 800 mg injection was prescribed, and n₃ = number of patients to whom the 800 mg tablets were prescribed. Numbers in green represent actual prescriptions that match the model prediction; those in red are non-matching actual prescriptions.

Table 4 Treatment response per AdoMet medication for the predicted categories produced by the MLR grid-optimization model

Predicted category	Actual prescription
	400 mg injection		800 mg injection		800 mg tablets
	Treatment response, % (95% CI)	N	Treatment response, % (95% CI)	N	Treatment response, % (95% CI)	N
I (clear preference for 400 mg injection)	72 (62–81)	86	86 (42–98)	7	67 (27–92)	6
II (clear preference for 800 mg injection)	50 (17–83)	6	47 (31–64)	34	50 (6–94)	2
III (clear preference for 800 mg tablets)	100	4	0	0	63 (28–87)	8
IV (reduced preference for 400 mg injection)	0	2	38 (13–72)	8	67 (27–92)	6
V (reduced preference for 800 mg injection)	93 (63–99)	14	100	3	71 (46–87)	17
VI (reduced preference for 800 mg tablets)	62 (40–80)	21	73 (51–87)	22	50 (17–83)	6
VII (indifference between treatments)	50 (17–83)	6	60 (30–84)	10	67 (27–92)	6

Note: 95% CIs were calculated as per binomial distribution.

Abbreviations: CI, confidence interval; MLR, multinomial logistic regression.

Table 5 Pairwise comparisons of response to AdoMet treatment

Category	400 mg injection, % (95% CI)	N	800 mg injection, % (95% CI)	N	800 mg tablets, % (95% CI)	N
IV and VII (indifference between 800 mg injection and 800 mg tablets)	–	–	50 (28–72)	18	67 (38–87)	12
V and VII (indifference between 400 mg injection and 800 mg tablets)	80 (57–92)	20	–	–	70 (48–85)	23
VI and VII (indifference between 400 mg injection and 800 mg injection)	59 (40–76)	27	69 (51–82)	32	–	–

Note: “–” indicates not applicable.

Abbreviation: CI, confidence interval.