The SONIC trial compared azathioprine, infliximab, and a combination of both for the treatment of moderate to severe Crohn's disease in patients who had not previously received biologics or immunosuppressants. It found that the combination of azathioprine and infliximab resulted in the highest rate of steroid-free remission at 26 weeks compared to either drug alone. Infliximab monotherapy led to higher rates of steroid-free remission than azathioprine alone. The trial demonstrated benefit for anti-TNF induction therapy in this patient population.

1. SONIC
HTTP://TRIALGURU.ORG
Colombel JF, et al. "Infliximab, azathioprine, or
combination therapy for Crohn's disease". The New
England Journal of Medicine. 2010. 362(15):1383-
1395.

2. 2010 Study of Biologic and Immunomodulator Naive Patients in Crohn
Disease (SONIC)

3. BACKGROUND
 Infliximab (anti-TNF-α monoclonal
antibody) as maintenance therapy for
Crohn disease has been established
 However, studying infliximab as an
induction agent has not been done

4. CLINICAL QUESTION
Among patients with
moderate to severe
Crohn disease without
prior treatment with
immunosuppressive
therapies or biologics,
does azathioprine,
infliximab, or a
combination of both
therapies improve
rates of steroid-free
remission?

5. DESIGN
 Analysis: Intention-to-treat
 Multicenter, randomized, double blind, comparative trial
 N=508 patients with Crohn disease
 Azathioprine (n=170)
 Infliximab (n=169)
 Combination therapy (N=169)
 Setting: 92 centers in multiple continents
 Enrollment: 2005-2008
 Follow-up: 26 weeks
 Primary outcome: Corticosteroid-free clinical remission at week 26

6. POPULATION
Inclusion Criteria
 Age ≥21 years
 Crohn's disease for ≥6 weeks
 Crohn's disease activity Index (CDAI)
score 220-450 off corticosteroids
 Out of a total score of 600, remission
<150 and severe >450
 One of the following:
 On steroids for disease control
 May need 2nd course of steroids in 1
year
 No response to ≥4 weeks of
Exclusion Criteria
 Treatment with 6MP, MTX, or anti-TNF
biologic
 Short gut, Ostomy, Symptomatic stricture
 Abscess, Abdominal surgery in prior 6
months
 Granulomatous infection including TB
 HIV, Hep B, Hep C
 Multiple sclerosis
 Cancer
 Mutant thiopurine methyltransferase
phenotype

7. INTERVENTIONS
 Randomized to a group with stratification by center, disease duration, and baseline
prednisone equivalent dosing:
 Infliximab - Infliximab 5 mg/kg IV at weeks 0, 2, 6, then q8 weeks, plus placebo tablets
 Azathioprine - Azathioprine 2.5 mg/kg qday, plus placebo infusions
 Combination - Infliximab plus azathioprine as above
 Oral mesalamine was continued at a stable dosing
 Corticosteroids and Budesonide continued, but at adjusted dosing
 Colonoscopy at baseline, repeated at week 26 for those with mucosal ulcers at baseline
 Groups were followed until week 30
 Participants had the option of continuing on their assigned therapies in a blinded fashion
until week 50 as part of an extension trial, though these results are out of the scope of
this review

8. RESULTS
Fig. 2A
 At week 26, a total of 96 of the 169 patients (56.8%)
receiving combination therapy, 75 of the 169 patients
(44.4%) receiving infliximab, and 51 of the 170 patients
(30.0%) receiving azathioprine were in corticosteroid-
clinical remission
 P=0.006 for the comparison of infliximab vs.
 P<0.001 for the comparison of combination therapy vs.
azathioprine
 P=0.02 for the comparison of combination therapy vs.
infliximab

9. RESULTS
Fig. 2B
 At week 26, mucosal healing had occurred in 47 of 107
patients (43.9%) receiving combination therapy, in 28 of
93 patients (30.1%) receiving infliximab, and in 18 of 109
patients (16.5%) receiving azathioprine
 P=0.02 for infliximab vs. azathioprine
 P<0.001 for combination therapy vs. azathioprine
 P=0.06 for combination therapy vs. infliximab

10. BOTTOM LINE
Patients with moderate to severe Crohn
disease who has NOT previously been
treated with immunosuppressives or
biologics, a combination of azathioprine and
infliximab resulted in a higher rate of
steroid-free remission at week 26 than
either drug alone.
Infliximab monotherapy showed longer
steroid free remission than azathioprine
monotherapy.

11. CRITICISMS
 Low rate of mucosal ulceration, which may be more likely attributable to IBS rather than
IBD
 Induction therapy only given to group getting Infliximab
 Azathioprine takes up to 6 month so trial not a fair comparison between azathioprine and
infliximab
 Unclear efficacy in patients with longer disease duration
 No cost analysis
 Funding for study:
 Centocor Ortho Biotech (now Janssen Biotech, sellers of Remicade in the US, the brand
name of infliximab)
 Schering-Plough (now owned by Merck, sellers of Remicade outside of the US)

12. DISCUSSION QUESTIONS
 What did the SONIC trial show?
 For patients with Crohn’s disease, should a
patient be given anti-TNF induction
therapy?
 According to the SONIC trial, are anti-TNF
better or worse than Azathioprine at
achieving steroid free remission?

13. DISCUSSION QUESTIONS/ANSWERS
 What did the SONIC trial show?
 ANSWER: It showed that a combination of
azathioprine and infliximab resulted in a
higher rate of steroid-free remission
 For patients with Crohn’s disease in the SONIC
trial, should a patient be given anti-TNF
induction therapy?
 ANSWER: Yes, anti-TNF induction should be
given
 According to the SONIC trial, are anti-TNF
better or worse than Azathioprine at achieving
steroid free remission?
 ANSWER: Anti-TNF (especially Infliximab
which was the study drug) was better at
achieving steroid free remission

14. BOARD-LIKE QUESTION
71yo women with history of Crohn disease
presents with B symptoms of fatigue,
unintentional weight loss, fever, night
sweats. Only medication is Infliximab
Physical exam:
T 37.9, HR 107, BP 108/61, RR 14. BMI 20.
Gen: NAD, thin
Diffuse lymphadenopathy, no
hepatosplenomegaly
Radiographs:
CT scan shows extensive lymphadenopathy
at cervical, axillary, abdominal, pelvis
Adapted from MKSAP 17
QUESTION
What is the most likely diagnosis?
A. Non-Hodgkin lymphoma
B. Sarcoidosis
C. Testicular cancer
D. Tuberculosis

15. BOARD-LIKE QUESTION
ANSWER
What is the most likely diagnosis?
A. Non-Hodgkin lymphoma
B. Sarcoidosis
C. Testicular cancer
D. Tuberculosis
Educational Objective:
Immunosuppression can lead to non-
Hodgkin lymphoma
Key Point:
- This patient has received long term
immunosuppression with Infliximab. Now
with B-symptoms, likely from NHL
- Viral infections (eg EBV, HIV, HTLV, Hep
B/C) can also drive transformation of
lymphoid tissue to lymphoma or
contribute indirectly by cause
immunodeficiency (risk for development
of lymphoma)

16. REFERENCES
 Thursz MR, et al. "Prednisolone or
pentoxifylline for alcoholic hepatitis". The
New England Journal of Medicine. 2015.
372(17):1619-1628.
 LLC PeripheralBrain.
https://www.wikijournalclub.org/wiki/SO
NIC