The treatment of disc-herniation-induced sciatica with infliximab: one-year follow-up results of FIRST II, a randomized controlled trial.
METHODS
A randomized controlled trial.


OBJECTIVE
To evaluate the long-term efficacy of infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-alpha), in patients with acute/subacute sciatica secondary to herniated disc.


BACKGROUND
The results of experimental studies and our open-label trial support the use of infliximab in sciatica. Here we report the 1-year results of a randomized controlled trial (FIRST II, Finnish Infliximab Related STudy) evaluating the efficacy and safety of a single infusion of infliximab for sciatic pain.


METHODS
Inclusion criteria were unilateral sciatic pain with a disc herniation concordant with the symptoms and signs of radicular pain. Patients had to be candidates for discectomy. Criteria for discectomy included (in addition to a symptomatic disc herniation on MRI) neural entrapment (straight leg raising [SLR] < or =60 degrees ) with either a short-term (2-4 weeks) severe or long-term (4-12 weeks) moderate leg pain. Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo. Differences in the clinical examination parameters (straight leg raise [SLR], muscle strength, sensory defects, tendon reflexes), patient-reported symptoms (leg and back pain using a visual analog scale [VAS], Oswestry disability, quality-of-life [RAND-36]), sick leaves, number of discectomies, and adverse effects between the two treatment groups over the 1-year follow-up were compared using Mann-Whitney U test or Student's t test, repeated-measures analysis, or Cox proportional hazards model. Logistic regression was used to assess the predictors of good response.


RESULTS
Sixty-seven percent of patients in the infliximab group reported no pain at 52 weeks compared with 63% in the control group (P = 0.72). Similar efficacy was observed between treatment groups for other outcomes. Eight patients in each group required surgery. Three nonserious adverse reactions were encountered in the infliximab group. The response (irrespective of the treatment) was significantly better with shorter symptom duration and less SLR restriction at baseline. Patients in the infliximab group appeared to especially benefit in cases of a L4-L5 (or L3-L4) herniation and if a Modic change was colocalized at the symptomatic level.


CONCLUSIONS
Although the long-term results of this randomized trial do not support the use of infliximab compared with placebo for lumbar radicular pain in patients with disc herniation-induced sciatica, further study in a subgroup of patients with L4-L5 or L3-L4 herniations, especially in the presence of Modic changes, appears to be warranted.
Korhonen
Timo
T
Department of Physical Medicine and Rehabilitation, Oulu University Hospital, Oulu, Finland.
Karppinen
Jaro
J
Paimela
Leena
L
Malmivaara
Antti
A
Lindgren
Karl-August
KA
Bowman
Chris
C
Hammond
Anthony
A
Kirkham
Bruce
B
Järvinen
Simo
S
Niinimäki
Jaakko
J
Veeger
Nic
N
Haapea
Marianne
M
Torkki
Markus
M
Tervonen
Osmo
O
Seitsalo
Seppo
S
Hurri
Heikki
H
D000208:Acute Disease; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D004198:Disease Susceptibility; D017586:Diskectomy; D005260:Female; D005500:Follow-Up Studies; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007239:Infections / Q000209:etiology; D000069285:Infliximab; D007405:Intervertebral Disc Displacement / Q000150:complications* / Q000188:drug therapy; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011788:Quality of Life; D020127:Recovery of Function; D012585:Sciatica / Q000188:drug therapy* / Q000209:etiology; D019467:Subacute Care; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab