View on the Treatment of Rheumatoid Arthritis with Baricitinib Using the NNT Indicator

Introduction

Treatment of RA with baricitinib brings rapid and long-term improvements in clinical parameters assessed by patients themselves (PROs – patient-reported outcomes), even for patients who have not shown an adequate response to methotrexate therapy or to biological disease-modifying antirheumatic drugs (bDMARDs).

In addition to specific clinical outcomes, the effectiveness of treatment can also be evaluated using the NNT (number needed to treat) parameter, which calculates the number of patients who must be treated with a given drug for at least one to achieve the desired effect. It is an epidemiological indicator that does not reflect the degree of effect in an individual but helps express the efficacy of a drug within the treated population. Calculation requires knowing the results of the control group. If the desired effect is achieved in every patient using the tested drug and in none of the control group, the NNT equals 1. The higher the NNT, the lower the observed efficacy in the population. Negative values indicate the tested drug is worse than the comparator.

Therapy Evaluation

The aim of the presented analysis was to determine the NNT value for achieving a predefined minimum clinically significant difference (MCID) in specific PROs at the 12th week of RA therapy. The intervention assessed was baricitinib at a daily dose of 2 or 4 mg compared to a placebo. Data were drawn from clinical trials RA-BEAM (patients unresponsive to methotrexate) and RA-BEACON (patients unresponsive to bDMARDs). A clinically significant outcome was defined as achieving an NNT value ≤ 10 compared to the placebo.

The following PROs were assessed:

• PtGA Score (Patient Global Assessment of Disease Activity) on a 0–100 mm scale, with MCID set at ≥ 10 mm compared to the placebo.
• Pain using a visual analog scale (VAS; 100 mm scale, MCID set at ≥ 10 mm compared to the placebo).
• Physical Function using the HAQ-DI (Health Assessment Questionnaire Disability Index; MCID set at ≥ 0.22 points compared to the placebo).
• Fatigue using the FACIT-F questionnaire (Functional Assessment of Chronic Illness Therapy-Fatigue; MCID set at ≥ 4 compared to the placebo).
• Health-Related Quality of Life using the SF-36 questionnaire (MCID set variably for overall score and individual subdomains).

Results and Conclusion

After 12 weeks, patients treated with baricitinib experienced statistically and clinically significant improvements in most assessed PROs, with the exception of some subdomains of quality of life (e.g., emotional functions and mental health), where results across groups were generally comparable. In the RA-BEAM study, more than 74% of patients achieved defined MCID in PtGA, pain, physical function, and quality of life parameters. In the RA-BEACON study, the percentage was slightly lower, ranging between 62 and 66%. A higher dose of baricitinib was associated with a higher rate of achieving MCID in most assessed parameters.

For most PROs, the NNT parameter was ≤ 10. For example, the NNT for PtGA and pain was around 4 in both studies, 4–6 for physical function, and similarly 4–7 for overall quality of life. NNT for fatigue stood out, being 14.1 in the RA-BEAM study and 6.9 in the RA-BEACON study for the higher dose of baricitinib.

The presented findings suggest that baricitinib is an effective treatment for RA patients unresponsive to methotrexate or bDMARDs. Fewer than 10 patients need to be treated for one to achieve a clinically significant benefit.

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Source: Strand V., Sun L., Ross Terres J., Kannowski C. L. FRI0048 Number needed to treat to achieve minimum clinically significant differences in patient-reported outcomes in patients treated with baricitinib. Ann Rheum Dis 2020; 79: 599–600, doi: 10.1136/annrheumdis-2020-eular.1440.