A 52-year-old woman with inadequately controlled rheumatoid arthritis comes to the clinic.… — USMLE Step 3

A 52-year-old woman with inadequately controlled rheumatoid arthritis comes to the clinic. Her physician is considering starting her on a newly approved oral Janus kinase (JAK) inhibitor. Before prescribing the medication, the physician reviews the published results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial that evaluated the safety and efficacy of the drug over a 52-week period.

The trial enrolled a total of $1,500$ patients who were randomized in a 1:1 ratio to receive either the JAK inhibitor or a placebo. The safety data regarding incident herpes zoster infections during the trial are summarized in the table below:

Group	Total Patients	Herpes Zoster Cases
JAK Inhibitor	750	45
Placebo	750	15

Based on these study results, what is the number needed to harm (NNH) for a herpes zoster infection?

Answer: 25

Answer

The number needed to harm (NNH) is the number of patients who need to be exposed to a risk factor (or treatment) over a specific period to cause one additional adverse event. It is calculated using the formula:

NNH = \frac{1}{ARI}

, where ARI is the Absolute Risk Increase. The ARI is the difference in adverse event rates between the treatment and control groups. In this trial, the event rate in the treatment group (EER) is

\frac{45}{750} = 0.06

. The event rate in the placebo group (CER) is

\frac{15}{750} = 0.02

. The ARI is

0.06 - 0.02 = 0.04

. Therefore, the

NNH = \frac{1}{0.04} = 25

. This means that for every 25 patients treated with the JAK inhibitor for 52 weeks, one additional patient will develop a herpes zoster infection compared to placebo.

Step-by-Step Solution

Calculate the Experimental Event Rate (EER)

EER = 45 / 750 = 0.06

To determine the incidence of the adverse event in the treatment group.

Calculate the Control Event Rate (CER)

CER = 15 / 750 = 0.02

To determine the background incidence of the adverse event in the placebo group.

Calculate the Absolute Risk Increase (ARI)

ARI = EER - CER = 0.06 - 0.02 = 0.04

To find the absolute difference in risk caused by the medication.

Calculate the Number Needed to Harm (NNH)

NNH = 1 / ARI = 1 / 0.04 = 25

To determine how many patients need to be treated to cause one additional adverse event.

Key Concept

Number Needed to Harm (NNH) is the inverse of the Absolute Risk Increase (ARI) and represents the number of patients who need to receive a treatment for one additional adverse event to occur.

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