REVIEW ARTICLE
The Efficacy and Safety of DFN-15 for the Treatment of
Migraine: A Meta-Analysis of Randomized Controlled Studies
Yili Deng, MD,* Yang Chen, MD,† Zeyan Peng, MD,† and Heng Yang, MD†
Objectives: The efficacy of DFN-15 for pain control of migraine remains
controversial. We conduct a systematic review and meta-analysis to explore
the influence of DFN-15 versus placebo on pain control in migraine patients.
Patients and Methods: We search PubMed, Embase, Web of Science,
EBSCO, and Cochrane Library databases through November 2019 for ran-
Downloaded from http://journals.lww.com/clinicalneuropharm by BhDMf5ePHKbH4TTImqenVHVWbIH6TTJXt+6jQbRDfKBmKA6t1O34KUxLV9xApgjoPLgRuwiiYmg= on 07/26/2020
domized controlled trials assessing the effect of DFN-15 versus placebo on
pain control in migraine patients. This meta-analysis is performed using the
random-effects model.
Results: Three randomized controlled trials are included in the meta-
analysis. Overall, compared with the control group in migraine patients,
lasmiditan treatment shows a positive impact on pain freedom at 2 hours (risk
ratio [RR], 1.96; 95% confidence interval, 1.61–2.40; P < 0.00001), head-
ache response at 2 hours (RR, 1.40; 95% CI, 1.25–1.57; P < 0.00001), and
pain freedom at 24 hours (RR, 1.87; 95% CI, 1.33–2.62; P = 0.0003), but
has no obvious influence or no substantial impact on no or mild disability
level (RR, 1.21; 95% CI, 0.97–1.52; P = 0.09) or nausea (RR, 2.42; 95%
CI, 0.53–11.01; P = 0.25). In addition, lasmiditan seems to result in the in-
crease in dizziness (RR, 7.33; 95% CI, 1.83–29.30; P = 0.005) and paresthe-
sia (RR, 5.17; 95% CI, 2.08–12.86; P = 0.0004).
Conclusions: DFN-15 treatment may be effective and safe for pain con-
trol in migraine patients.
Key Words: DFN-15, migraine, pain control, randomized controlled trials
(Clin Neuropharm 2020;43: 107–111)
M igraine is one common neurological disorder and is regarded
as the world's second leading cause of disability.1–5 Inflam-
matory mediators have important roles in the pathophysiology of
migraine.6–8 Certain nonsteroidal anti-inflammatory drugs (eg, as-
pirin, diclofenac, ibuprofen, and naproxen) are currently used for
the acute treatment of migraine by inhibiting the synthesis of pros-
taglandins by blocking the effects of cyclooxygenase (COX)-1 and
COX-2 on arachidonic acid.9–11
Celecoxib, a selective COX-2 inhibitor, demonstrates lower
risk of gastrointestinal events than naproxen or ibuprofen
(P = 0.002), and lower risk of renal events than ibuprofen for os-
teoarthritis and rheumatoid arthritis.12,13 Celecoxib is also indi-
cated for the control of acute pain in patients with ankylosing
spondylitis and primary dysmenorrhea. DFN-15, an oral liquid
solution of celecoxib, has some potential in the acute treatment
of migraine. During the acute treatment of migraine, 120 mg
DFN-15 can remarkably improve pain freedom at 2 hours and
freedom from the most bothersome symptom (MBS).14
Several studies have investigated the effects of DFN-15 on
pain relief for migraine patients.14–16 This systematic review and
*Department of Cardiology, Xinxin Hospital of Qijiang District; and †Department
of Neurology, Daping Hospital, Army Medical University, Chongqing, China.
Address correspondence and reprint requests to Heng Yang, MD, Department of
Neurology, Daping Hospital, Army Medical University, Chongqing
400042, China; E‐mail: cyfy776655@163.com
Conflicts of Interest and Source of Funding: The authors have no conflict of
interest to declare.
Research involving human participants and/or animals: not applicable.
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
DOI: 10.1097/WNF.0000000000000401
Clinical Neuropharmacology • Volume 43, Number 4, July/August 2020
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
meta-analysis of randomized controlled trials (RCTs) aims to as-
sess the efficacy and safety of DFN-15 versus placebo on pain
control in migraine patients.
MATERIALS AND METHODS
This systematic review and meta-analysis are performed
based on the guidance of the Preferred Reporting Items for Sys-
tematic Reviews and Meta-analysis statement and Cochrane
Handbook for Systematic Reviews of Interventions.17,18 No ethical
approval and patient consent are required because all analyses are
based on previous published studies.
Literature Search and Selection Criteria
We systematically search several databases including
PubMed, Embase, Web of Science, EBSCO, and the Cochrane Li-
brary from inception to November 2019 with the following key-
words: DFN-15 and migraine. The reference lists of retrieved
studies and relevant reviews are also hand-searched, and the afore-
mentioned process is performed repeatedly in order to include ad-
ditional eligible studies.
The inclusion criteria are presented as follows: (1) study de-
sign is RCT, (2) patients are diagnosed with migraine, and (3) in-
tervention treatments are DFN-15 versus placebo.
Data Extraction and Outcome Measures
Some baseline information is extracted from the original
studies, including first author, number of patients, age, body mass
index, and detailed methods in 2 groups. Data are extracted inde-
pendently by 2 investigators, and discrepancies are resolved by
consensus. We have contacted the corresponding author to obtain
the data when necessary.
The primary outcome is 2-hour pain freedom. Secondary
outcomes include freedom from MBS, adverse event, dysgeusia,
and nausea.
Quality Assessment in Individual Studies
The methodological quality of each RCT is assessed using the
Jadad scale, which consists of 3 evaluation elements: randomization
(0–2 points), blinding (0–2 points), and dropouts and withdrawals
(0–1 points).19 One point would be allocated to each element if they
have been conducted and mentioned appropriately in the original
article. The Jadad scale score varies from 0 to 5 points. An article
with Jadad score ≤2 is considered to be of low quality. The study
is thought to be of high quality if the Jadad score is ≥3.20
Statistical Analysis
We assess risk ratios (RRs) with 95% confidence intervals
(CIs) for dichotomous outcomes (2-hour pain freedom, freedom
from MBS, adverse event, dysgeusia, and nausea). Heterogeneity
is evaluated using the I2 statistic, and I2 > 50% indicates signifi-
cant heterogeneity.21 The random-effects model is used for all
meta-analyses. We search for potential sources of significant het-
erogeneity. Sensitivity analysis is performed to detect the
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Deng et al Clinical Neuropharmacology • Volume 43, Number 4, July/August 2020

FIGURE 1. Flow diagram of study searching and selection process.

influence of a single study on the overall estimate via omitting one
study in turn or performing the subgroup analysis. Because of the
limited number (<10) of included studies, publication bias is not
assessed. Results are considered statistically significant for
P < 0.05. All statistical analyses are performed using Review
Manager Version 5.3 (The Cochrane Collaboration, Software Up-
date, Oxford, United Kingdom).
RESULTS
initially, and 2 RCTs and 1 abstract are included in the meta-
analysis.14–16
The baseline characteristics of 3 included RCTs are shown in
Table 1. These studies are published between 2017 and 2019, and
the total sample size is 711. DFN-15 is administered by a single
dose of DFN-15 120 mg. Three RCTs report 2-hour pain freedom
and freedom from MBS,14–16 and 2 RCTs report adverse events,
dysgeusia and nausea.14,16 The Jadad scores of the 3 included
studies vary from 3 to 5, and all 3 studies have high quality based
on the quality assessment.

Literature Search, Study Characteristics, and Primary Outcome: 2-Hour Pain Freedom
Quality Assessment The random-effects model is used for the analysis of primary
Figure 1 shows the detailed flowchart of the search and selec- outcomes. The results find that compared with the control group
tion results. Forty-five potentially relevant articles are identified in migraine patients, a single dose of DFN-15 120 mg is

TABLE 1. Characteristics of Included Studies

DFN-15 Group Control Group

Female, Female, Jada
No. Author No. Age, y n BMI, kg/m2 Methods No. Age, y n BMI, kg/m2 Methods Scores
1 Bennett and 20 — — — 120 mg DFN-15 daily 20 — — — Placebo 3
Munjal15
2 Lipton et al14 285 41 (11) 252 30.6 (7.8) 120 mg DFN-15 daily 282 40 (12) 242 30.0 (7.9) Placebo 5
3 Munjal and 51 43.6 — 28.48 Single dose of 53 43.6 — 28.48 Placebo 4
Bennett16 DFN-15 120 mg
BMI, body mass index.

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Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Clinical Neuropharmacology • Volume 43, Number 4, July/August 2020
FIGURE 2. Forest plot of the meta-analysis of 2-hour pain freedom.
FIGURE 3. Forest plot of the meta-analysis of freedom from MBS.
associated with significantly improved 2-hour pain freedom (RR,
1.65; 95% CI, 1.28–2.12; P = 0.0001) with no heterogeneity
among the studies (I2 = 0%; heterogeneity, P = 0.98; Fig. 2).
Sensitivity Analysis
There is no heterogeneity for the primary outcome, and thus,
we do not perform the meta-analysis via omitting one study or
subgroup analysis to detect the heterogeneity.
Secondary Outcomes
In comparison with the control intervention for migraine,
DFN-15 treatment can substantially increase freedom from MBS
(RR, 1.40; 95% CI, 1.12–1.76; P = 0.003; Fig. 3), but has no sub-
stantial impact on adverse events (RR, 1.34; 95% CI, 0.88–2.04;
P = 0.17; Fig. 4), dysgeusia (RR, 2.20; 95% CI, 0.97–5.00;
P = 0.06; Fig. 5), or nausea (RR, 1.44; 95% CI, 0.54–3.85;
P = 0.47; Fig. 6).
DISCUSSION
Compared with the oral capsule formulation of celecoxib,
120 mg DFN-15 (50 mg/mL) has a faster median time to peak
concentration (within 1 vs 2.5 hours), which affords more rapid
onset of pain relief and a treatment priority for people with mi-
graine.22,23 DFN-15 120 mg had a relative bioavailability of
144% (ie, 44% greater) compared with a 400-mg dose of
FIGURE 4. Forest plot of the meta-analysis of adverse events.
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Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
DFN-15 for Migraine Treatment
celecoxib oral capsules20 and may result in low incidence of ad-
verse events.22
Our meta-analysis suggests that DFN-15 at a single dose of
120 mg is associated with substantially improved 2-hour pain
freedom and freedom from MBS for the acute treatment for mi-
graine patients. In addition, DFN-15 is also documented to pro-
vide significantly benefit to change in functional disability, relief
of photophobia, 24-hour satisfaction with treatment, use of rescue
medication, and sustained pain relief and pain freedom.14
Migraine patients commonly have some problems of cardio-
vascular conditions, events, and procedures.24–28 Widely used
triptans may even increase the risk of serious cardiovascular ad-
verse events by vasoconstriction and the activation of 5-HT1B
receptors.29–31 Long-term use of nonsteroidal anti-inflammatory
drugs (eg, COX-2–selective drugs) should be used with caution
in patients with cardiovascular risk factors. Two cardiovascular
events (eg, palpitation and hypertension) were reported to be very
low and similar between DFN-15 and placebo for migraine
patients.16
Furthermore, this meta-analysis finds no statistical difference
of adverse events, dysgeusia, or nausea between the 2 groups.
Dysgeusia and nausea are the most common adverse events dur-
ing DFN-15 treatment. The tolerability and safety of DFN-15
are generally favorable, with mostly mild adverse events. Several
limitations exist in this meta-analysis. First, our analysis is based
on only 3 RCTs, and more RCTs with large sample size should
www.clinicalneuropharm.com 109
Deng et al
FIGURE 5. Forest plot of the meta-analysis of dysgeusia.
FIGURE 6. Forest plot of the meta-analysis of nausea.
be conducted to explore this issue. Next, although there is no het-
erogeneity, different patient population may lead to some bias. Fi-
nally, some unpublished and missing data may induce some bias
to the pooled effect.
CONCLUSIONS
DFN-15 treatment may be effective and safe for pain control
in migraine patients.
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