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Successful treatment with intraarticular infliximab for resistant knee monarthritis in a patient with spondylarthropathyA role for scintigraphy with 99mTc-infliximab.

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ARTHRITIS & RHEUMATISM
Vol. 52, No. 4, April 2005, pp 1224–1226
DOI 10.1002/art.20979
© 2005, American College of Rheumatology
Successful Treatment With Intraarticular Infliximab for
Resistant Knee Monarthritis in a Patient With
Spondylarthropathy
A Role for Scintigraphy With
99m
Tc-Infliximab
Fabrizio Conti, Roberta Priori, Maria Sole Chimenti, Giulio Coari, Alessio Annovazzi,
Guido Valesini, and Alberto Signore
Positive experiences with intraarticular infliximab have been reported in patients with rheumatoid
arthritis, ankylosing spondylitis, and Behçet’s disease.
We used intraarticular infliximab to treat resistant knee
monarthritis in a patient with spondylarthropathy.
Clinical and laboratory improvement was associated
with improvement in scintigraphic findings. This approach is less expensive than intravenous administration of infliximab. We suggest that selection of candidates for this innovative therapy should be guided by
anti–tumor necrosis factor ␣ scintigraphy.
riences with intraarticular infliximab in patients with RA,
AS, and Behçet’s disease have been reported (8–11).
CASE REPORT
The patient, a 34-year-old HLA–B27–positive
white man, had undifferentiated spondylarthropathy.
His clinical history began 2 years previously, with left
knee arthritis, buttock pain, inflammatory spinal pain,
and recurrent right iritis. During these years he was
treated with oral steroids and sulfasalazine and experienced global improvement except for the left knee
arthritis, with relapses occurring more and more frequently. At the time of admission to our rheumatology
division in December 2003, the patient was receiving
sulfasalazine 4 gm daily and rofecoxib 50 mg daily. He
presented with arthritis of the left knee and back pain at
night. He had experienced a flare of uveitis during the
last 2 months and was treated with local and systemic
steroids.
Laboratory findings included an erythrocyte sedimentation rate (ESR) of 20 mm/hour and a C-reactive
protein (CRP) level of 9 mg/dl. Ultrasonography of the
involved knee showed synovial thickening, proliferation,
a large effusion, and power Doppler positivity (Figure
1A). An arthrocentesis was performed, and 50 ml of
inflamed sterile synovial fluid was extracted. Intramuscular methotrexate, 15 mg weekly, was added to the
regimen of sulfasalazine and rofecoxib. After 3 months,
the patient experienced frank improvement of the spinal
pain, and no recurrence of iritis was observed. However,
arthritis in the left knee persisted in spite of a 40-mg
intraarticular injection of methylprednisolone acetate
Tumor necrosis factor ␣ (TNF␣) plays a central
role in the pathogenesis of synovial inflammation, and
the levels of TNF␣ are increased in inflamed joints (1,2).
During the past few years, intravenous infliximab, a
chimeric monoclonal antibody against TNF␣, has become a well-established treatment for rheumatoid arthritis (RA) (3) as well as other inflammatory polyarthritides such as psoriatic arthritis (4), ankylosing
spondylitis (AS) (5), undifferentiated spondylarthropathies (6), and spondylarthropathies associated with
Crohn’s disease (7). More recently, some positive expeFabrizio Conti, MD, Roberta Priori, MD, Maria Sole Chimenti, MD, Giulio Coari, MD, Alessio Annovazzi, MD, Guido
Valesini, MD, Alberto Signore, MD: Università degli Studi di Roma
“La Sapienza,” Rome, Italy.
Drs. Conti and Priori contributed equally to this work.
Address correspondence and reprint requests to Alberto
Signore, MD, Medicina Nucleare, Dipartimento Scienze Cliniche,
Università degli Studi “La Sapienza,” Policlinico Umberto I, Viale del
Policlinico 155, 00161 Rome, Italy. E-mail: alberto.signore@
uniroma1.it.
Submitted for publication October 26, 2004; accepted in
revised form January 14, 2005.
1224
INTRAARTICULAR INFLIXIMAB IN SpA
1225
Figure 1. Ultrasonography of the affected knee before (A) and after (B) intraarticular injection of
infliximab. Intraarticular infliximab administration resulted in a dramatic reduction in thickness
and amelioration of proliferation in the synovial membrane, disappearance of the initial large
effusion, and negative power Doppler results.
(the degree of swelling and tenderness was graded as
severe, and the pain score on a 100-cm visual analog
scale [VAS] was 52). Use of an intraarticular TNF␣
antagonist was proposed.
In order to assess the degree of TNF␣ expression
in the affected knee, we performed scintigraphy with
99m
Tc-infliximab. Infliximab was radiolabeled using a
direct labeling method, as previously described (12).
After in vivo injection of 15 mCi of 99mTc-infliximab,
planar images of the knees were acquired at 6 and 24
hours. Scintigraphy showed an intense accumulation of
the radiopharmaceutical agent in the left knee, indicating high levels of intralesional TNF␣ (Figure 2A).
Negative results of tuberculin skin testing and normal
results of chest radiography were also obtained. After
the patient gave informed consent, 80 ml of synovial
fluid was removed, and 100 mg of infliximab mixed with
10 ml of sterile water, according to the manufacturer’s
Figure 2. Scintigraphy with 99mTc-infliximab before (A) and 4 months after (B) intraarticular
administration of infliximab. Strong uptake of 99mTc-infliximab is detectable in the left knee in the
scintigraph obtained before therapy (A), while no uptake can be observed in the second scan (B),
confirming the complete remission.
1226
CONTI ET AL
instructions, was injected into the left knee as a single
dose. The treatment was well tolerated, and no adverse
reaction occurred locally or systemically.
The patient was reevaluated after 7 and 15 days,
then monthly for 4 months, and then bimonthly, for a
total of 8 months of followup. Complete remission of
knee arthritis was observed each time (VAS score for
pain ⫽ 0; no swelling or tenderness). Because of the
dramatic improvement that was observed, rofecoxib was
stopped 10 days after administration of infliximab. After
4 months of followup, both the ESR and the CRP level
were normal, and ultrasonography revealed a reduction
in thickness and amelioration of proliferation in the
synovial membrane; results of power Doppler imaging
were negative (Figure 1B). At that time, a new scintigraph with 99mTc-infliximab showed no accumulation of
the radiopharmaceutical agent in the knees, indicating
the absence of detectable levels of TNF␣ (Figure 2B)
and confirming the efficacy of intraarticular infliximab
treatment in the previously affected knee. After an
additional 4 months, the patient is still asymptomatic,
with no signs of active knee arthritis.
DISCUSSION
Intraarticular infliximab proved to be effective in
this case of refractory knee synovitis in a patient with
undifferentiated spondylarthropathy. In a previous report, this new therapeutic approach failed in a group of
6 patients with different types of arthritis, including 4
cases of spondylarthropathy (13). Our patient was
treated with both sulfasalazine and methotrexate for
more than 3 months, a treatment that was able to
improve all of the patient’s clinical signs and symptoms
(buttock pain, spinal pain, and recurrent right iritis)
except the left knee arthritis. Knee synovitis that was
unresponsive to systemic therapy did not resolve after
the patient received an intraarticular steroid injection.
The demonstration of high levels of TNF␣ in only the
affected knee, using radiolabeled anti-TNF␣ scintigraphy, prompted us to use intraarticular infliximab in this
patient. The impressive and sustained clinical response
demonstrated the central role of TNF␣ in the pathogenesis of this kind of monarthritis. The clinical and laboratory improvement was associated with improvement in
scintigraphy findings, which showed the absence of
detectable levels of TNF␣ in the affected knee. The
good clinical outcome was confirmed by power Doppler
sonography.
This report, together with several previous re-
ports (8–11), supports the use of intraarticular infliximab
in selected cases of inflammatory monarthritis resistant
to traditional therapeutic approaches. In this case, a
single 100-mg intraarticular injection of infliximab led to
a prolonged clinical response at a dramatically lower
cost than that associated with the intravenous approach,
and avoiding further hospitalization. We suggest that the
selection of patients who are candidates for this innovative intraarticular therapy should be guided by antiTNF␣ scintigraphy, although large placebo-controlled
studies are required to better define the diagnostic and
prognostic criteria.
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treatment, patients, resistance, infliximab, 99mtc, knee, successful, role, monarthritis, spondylarthropathya, scintigraphy, intraarticular
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