Effects of ruxolitinib on infection in patients with myeloproliferative neoplasm: a meta-analysis

Figures & data

Figure 1. Selection process.

Table 1. Characteristics of included research studies.

Table 1A. Patients’ characteristics at the early stage of the study
Trial name	Publication year	Primary sample size		Age		Treatment		Disease	Data cut-off	Crossover	Overall infection (N)		Herpes zoster infection (N)
		RUX	Control	RUX	Control	RUX	Control				RUX	Control	RUX	Control
COMFORT I	2012	155	154	66 (43–91)	70 (40–86)	Initial dose: 15 or 20 mg bid (twice daily)	Placebo	MF	All patients completed 24 weeks therapy and half of patients completed the 36-week therapy	16 patients crossovered before 24 week and 20 patients crossovered after 24 week	17	11	NR	NR
COMFORT II	2012	146	73	67 (35–83)	66 (35–85)	Initial dose: 15 or 20 mg bid	BAT	MF	All patients completed the 48-week follow-up	Anytime	64	32	NR	NR
RESPONSE	2015	110	112	62 (34–90)	60 (33–84)	Initial dose: 10 mg bid	BAT	PV	All patients completed the 48-week follow-up or discontinued	Allowed after 32 week	46	41	7	0
RESPONSE II	2016	74	75	63 (54–71)	67 (61–74)	Initial dose: 10 mg bid	BAT	PV	All patients completed the 28-week therapy	Allowed after 28 week	19	21	1	0
RELIEF	2017	54	56	64 (36–87)	66 (19–85)	Ruxolitinib + placebo	HU + placebo	PV	After the 48-week therapy	Allowed after 16 week	1	0	1	0
MAJIC-ET	2017	58	57	65.6 ± 13.5	62.9 ± 12.3	Initial dose: 20 or 25 mg bid	BAT	ET	2-year follow-up	Not permitted	9	2	NR	NR
Table 1B. Patients’ characteristics in the extension phase of the study.
Trial name	Publication year	Patient-year of exposure		Data cut-off	Patients Crossover into RUX group	Overall infection events (N)		Herpes zoster infection events (N)
		RUX	Control			RUX	Control	RUX	Control
COMFORT I	2017	452.5	104.1	5-year follow-up	111	227	64	16	1
COMFORT II	2013	304.87	66.98	3-year follow-up	45	140	35	NR	NR
COMFORT II^a	2016	409.52	66.98	5-year follow-up	45	/	/	16	0
RESPONSE	2016	227.7	73.6	80-week follow-up	98	67	43	12	0
RESPONSE II	2018	132.59	53.36	80-week follow-up	58	33	18	5	0

Notes: NR: Not reported, RUX: Ruxolitinib, BAT: Best available therapy, HU: hydroxyurea, PV: polycythemia vera, MF: myelofibrosis, ET: essential thrombocythemia.

^a The results of COMFORT II published in 2016 were enrolled in the analysis of herpes zoster infection due to the lack of herpes zoster information in the 2013 publication. The risk of overall infection in the extension phase was evaluated by the results published in 2013 of COMFORT II study.

Figure 2. Funnel plot.

Table 2. Assessment of bias risk.

	Random sequence generation (selection bias)	Allocation concealment (selection bias)	Blinding of participants and personnel (performance bias)	Blinding of outcome assessment (detection bias)	Incomplete outcome data (attrition bias)	Selective reporting (reporting bias)	Other bias
COMFORT I	Low risk	Low risk	Low risk	Unclear	Low risk	High risk	Unclear
COMFORT II	Low risk	Unclear	Unclear	Unclear	High risk	High risk	Unclear
RESPONSE	Low risk	Unclear	Unclear	Unclear	Low risk	High risk	Unclear
RESPONSE II	Low risk	High risk	High risk	Unclear	Low risk	High risk	Unclear
MAJIC-ET	Low risk	High risk	High risk	Unclear	Low risk	Low risk	Unclear
RELIEF	Low risk	Low risk	Low risk	Unclear	High risk	High risk	Unclear

Figure 3. Risk of overall infection in patients receiving ruxolitinib. (A) Indicated the risk of overall infection at the early stage, and the odds ratio was calculated by the total number of patients. (B) Depicted the risk of overall infection in the extension phase, and the Odds ratio was evaluated by the patient-year of exposure.

Figure 4. Risk of herpes zoster infection in patients receiving ruxolitinib. (A) Indicated the risk of herpes zoster infection at the early stage, and the odds ratio was calculated by the total number of patients. (B) Depicted the risk of herpes zoster infection in the extension phase, and the odds ratio was evaluated by the patient-year of exposure.