Effect of Anti TNFa Upon Deep Endometriosis Associated Pain
Effect of Anti TNFa Upon Deep Endometriosis Associated Pain
Deep endometriosis associated pain is believed to be caused by inflammation. Anti TNFa has
 been proved to be an effective treatment for other inflammation related conditions as Crohn's
 disease Endometriosis is associated with an inflammatory response in the pelvis, which is
 mediated by a number of cytokines including TNF-α. It has therefore been suggested that
 infliximab, an anti-TNF-α monoclonal antibody, might relieve pain in affected women.
In this pilot study, 21 women with severe endometriosis-associated pain and a rectovaginal
 nodule, at least 1 cm in diameter on clinical examination, were randomised in a 2 to 1 ratio
 to receive intravenous infliximab (n=14) or placebo (n=7) in the three months prior to
 laparoscopic laser excision of the nodule.

 After a 1 month observation period, all women received three infusions of infliximab (5mg/kg)
 or placebo over the course of 6 weeks. Surgery was performed 3 months later and follow-up
 continued for a further 6 months. The primary endpoint was the total pain burden
 (dysmenorrhoea, deep dyspareunia and non-menstrual pain) rated on a daily basis by the
 patient using standard pain scales and analgesic intake as the outcome measures . Secondary
 endpoints included the volume of the endometriotic nodule assessed clinically and on
 transvaginal ultrasound, the amount of pelvic tenderness on clinical examination and the
 presence of other endometriotic lesions at laparoscopy.
Inclusion Criteria:

 -  The patients (aged 18-50 years) were all recruited from a single, tertiary referral
 hospital at Leuven University, Belgium, specialising in the surgical treatment of
 severe endometriosis.

 -  All the women were symptomatic and scheduled for surgical excision of a rectovaginal
 nodule, at least 1 cm in diameter, diagnosed on the basis of clinical examination at
 the time of menstruation.

 -  All the women had a menstrual cycle occurring every 25 to 40 days.

 -  If previously treated with hormonal medication for endometriosis, at least 3 months
 must have elapsed and they must have had at least two menstrual cycles since stopping
 treatment.

 -  Unless the women had previously been sterilised, they had to agree to use a
 double-barrier method of contraception for the duration of the study and for up to 6
 months after receiving the last infusion.

 -  The study was approved by the Institutional Review Board of Leuven University.

 -  Written, informed consent was obtained before any study related procedures were
 performed.

 Exclusion Criteria:

 -  Evidence on chest x-ray in the previous 3 months of old or currently active TB, or
 other history/evidence of active TB, even if adequately treated

 -  Evidence of serious infections (such as pneumonia or pyelonephritis) in the previous 3
 months

 -  Evidence of a documented HIV infection, active hepatitis-B or C, or an opportunistic
 infection (e.g. herpes zoster, cytomegalovirus, pneumocystis carinii, aspergillosis,
 histoplasmosis, or mycobacteria other than TB) in the previous 6 months

 -  Previous transplant surgery, a lymphoproliferative disorder or other malignancy

 -  Positive cervical cytology in the previous 6 months

 -  Previous treatment with infliximab, any drug known to affect TNF-α levels, e.g.
 pentoxifylline, thalidomide and etanercept, or any human/murine recombinant products

 -  Known allergy to murine products

 -  Use of other investigational drugs within 1 month of recruitment or within 5
 half-lives of the investigational agent, whichever was longer

 -  Any haematological or biochemical abnormalities on routine screening.

 -  Subjects were also excluded if there was any pelvic pathology on transvaginal
 ultrasound scan (TVS) other than small uterine fibroids (< 4 cm in diameter) and an
 ovarian endometrioma or endometriotic nodule.