BHCG MONITORING AFTER SINGLE DOSE METHOTREXATE TREATMENT OF TUBAL ECTOPIC PREGNANCY : IS THE DAY 4 BHCG NECESSARY? A RETROSPECTIVE COHORT STUDY

Dr Monique Atkinson, Dr Sarika Gupta, Dr Therese McGee

Westmead Hospital

BACKGROUND

Observing a minimum 15% fall in bHCG between Day 4-7 is the most commonly employed monitoring regime overall success rate with one dose is 70-75% Success improves to 90% with 2 doses but only

15-20% of women require a second dose

THE QUESTION IS.....

Why perform the Day 4 blood test if no decisions to

give a second dose of MTX are made until Day 7?

Is there an alternative?

UpToDate says a 25% fall in bHCG Day 1-7is as good as 15% fall Day 4-7 in predicting theneed for additional doses of MTX

Would be great if it were true, but is it?

Truthfully, no data exists (even in UpToDate) toevaluate this

So we decided to investigate.....

THE ANSWER IS.....

AIMS

To determine the optimal monitoring regime after single dose methotrexate therapy in tubal ectopic pregnancy management

Compare traditional monitoring regimen (i.e. 15% fall bHCG day 4-7 after treatment) with other regimens previously described in the literature 25% fall bHCG day 0/1-7 Any fall bHCG day 0/1-4 20% fall bHCG day 0/1-4 Any fall bHCG day 0/1-7 (a novel regimen

proposed by Westmead Hospital)

METHODS

Retrospective cohort study

Data collected on all women who received MTX in EPAC from 1st January 2010-15th October 2013 based on pharmacy records

Medical file and hospital electronic results were reviewed

METHODS

Inclusion Criteria Exclusion Criteria

• US diagnosed EP• Pre treatment bHCG <6000 IU/L

• Pregnancy of unknown location (PUL)• Missing critical bHCG levels • Women whose EP may reasonably have resolved with expectant management*

*bHCG fallen by >10% prior to therapy OR *Solitary low bHCG <1000 IU/L prior to MTX administration with no plateau or rise in level

METHODS

Note...

Prior to August 2012 day of administration at our institution was designated Day 0

Thereafter it was designated Day 1 in keeping with most published regimens

This degree of variation in nomenclature of the day of administration exists in the literature, hence both groups of women were included in our analysis

METHODS

What we reviewed

bHCG on Day 0/1, Day 4, Day 7

Other bloods pre-treatment and Day 7 Hemoglobin Platelets Neutrophils liver function tests

METHODS

Study Outcomes

*EP resolved without requiring surgical intervention

EP resolved with either one or two doses of MTX

1. Incidence of treatment success* for each regime

2. Comparison of treatment success incidence between regimes

3. Ability of each regime to appropriately select women for second doses of MTX

METHODS

Statistical analyses performed using McNemar’s test

RESULTS

Pharmacy records identified 142 eligible files After exclusions (mostly PULs), 88 files

remained for review In terms of methotrexate administration

55 women were designated Day 0 33 women were designated Day 1

In terms of follow up bloods 80 were collected on Day 4/7 8 were collected +/- 1 day either side

RESULTS

Outcome 1: Incidence of treatment success 92% of all cases (n=81/88) resolved without

surgery

8% (7/88) progressed to surgery 1 case of significant hemoperitoneum (tubal rupture Day

17)

6 cases with no rupture or significant hemoperitonem Indications for surgery: rising bHCG (2), severe pain after 2

doses MTX, anxiety (2), mis-diagnosis (E Coli pyelopehritis)

Complications No cases of clinically significant toxicity 6/88 (7%) had >2 x elevations in LFTs, all

spontaneously resolved

RESULTS Outcome 2: Relative efficacy of various

regimes inpredicting treatment success with MTX

RESULTS

Outcome 3: comparison of how regimes informprescription of second MTX doses

WHAT DOES THIS MEAN?

FIRSTLY

All regimens appropriately predict cases that don’t

require surgery (positive predictive value) andcorrectly identify those women who require

surgery(specificity)

SECONDLY

Some regimes overselected women forsecond doses of MTX including:

Day 0/1-7 25% fall (yes, the UpToDate one) Day 0/1-4 falls (any fall and 20% fall)

Any fall Day 0/1-7 and 15% fall Day 4-7 regimes

are significantly more selective so that fewerwomen need additional MTX

HOWEVER

15% fall Day 4-7 regime requires women to have an

additional blood test on Day 4

BUT

The novel regime ‘any fall bHCG between Day 0/1-7’ effectively predicts treatment

successand avoids the extra blood test on Day 4

So we propose it gets a gold medal.

WHY YOU SHOULD BELIEVE US

Study strengths Large sample size (other studies only 40-50

persons) Only US proven ectopics with plateaued or rising

bHCG were included

Study limitations Retrospective analysis (can’t measure pt anxiety) Using surgery as an endpoint to define treatment

success can be problematic as some indications for surgery vary between institutions such as patient anxiety and consultant response to borderline bHCG reductions

CONCLUSION

All regimes have good PPV (predict surgery avoidance) and specificity (don’t miss the need for surgery)

Some regimes overselect women for 2nd dose MTX

Of the two best regimes that correctly select women for surgery without overselecting them for additional doses of MTX, the Day 0-7 regime provides convenience and cost advantages by eliminating the need for Day 4 bHCG testing

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QUESTIONS