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. 2016 Apr 26;2(1):e000232.
doi: 10.1136/rmdopen-2015-000232. eCollection 2016.

Relationship between clinical and patient-reported outcomes in a phase 3 trial of tofacitinib or MTX in MTX-naïve patients with rheumatoid arthritis

Roy Fleischmann  1 , Vibeke Strand  2 , Bethanie Wilkinson  3 , Kenneth Kwok  4 , Eustratios Bananis  5
Affiliations

Relationship between clinical and patient-reported outcomes in a phase 3 trial of tofacitinib or MTX in MTX-naïve patients with rheumatoid arthritis

Roy Fleischmann et al. RMD Open. .

Abstract

Objective: To compare the relationship between clinical measures and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) treated with tofacitinib or methotrexate (MTX).

Methods: In a phase 3 randomised controlled trial, patients (N=956) who were MTX-naïve or had received ≤3 doses were randomised and received tofacitinib 5 or 10 mg twice daily or MTX titrated to 20 mg/week. Outcomes included: per cent of patients achieving American College of Rheumatology 70% responses (ACR70), ACR50, low disease activity (LDA) by Simplified Disease Activity Index (SDAI ≤11) and Clinical Disease Activity Index (CDAI ≤10), remission by SDAI (≤3.3) and CDAI (≤2.8), patient-reported Health Assessment Questionnaire-Disability Index (HAQ-DI scores <0.5), pain and global assessment of disease activity.

Results: At month 6, most patients who achieved LDA/remission by one definition achieved LDA/remission with others; however, discordance between measures was greater with MTX than with tofacitinib. As expected, concordance between CDAI and SDAI responses was high. Overall, patients achieving LDA or ACR50 responses reported less improvement in PROs (HAQ-DI, pain and patient global assessment) compared with clinical measures (tender and swollen joint counts).

Conclusions: Variability in levels of responses between clinical outcomes and PROs should be considered when setting treat-to-target goals in patients with RA.

Trial registration number: NCT01039688; Post-results.

Keywords: DMARDs (synthetic); Methotrexate; Patient perspective; Rheumatoid Arthritis.

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Figures

Figure 1
Figure 1
Percentage of responders at month 6 by (A) ACR50, SDAI/CDAI LDA, and HAQ-DI <0.5 and (B) ACR70, SDAI/CDAI REM, and HAQ-DI <0.5. ACR, American College of Rheumatology; BID, twice daily; CDAI, Clinical Disease Activity Index; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA, low disease activity; MTX, methotrexate; N, number of patients in analysis; REM, remission; SDAI, Simplified Disease Activity Index.
Figure 2
Figure 2
Improvement in PROs, TJC, SJC and PGA at month 6 in patients achieving (A) ACR50, (B) CDAI LDA and (C) HAQ-DI <0.5. For tofacitinib 5 and 10 mg BID treatment groups, low levels of improvement in PROs, TJC, SJC and PGA are reported in patients who were not responsive to the first clinical outcome. ACR, American College of Rheumatology; BID, twice daily; CDAI, Clinical Disease Activity Index; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA, low disease activity; MTX, methotrexate; PGA, physician's global assessment; PROs, patient-reported outcomes; PtGA, patient global assessment; SJC, swollen joint count; TJC, tender joint count.
Figure 3
Figure 3
Improvement in PROs, TJC, SJC and PGA at month 6 in patients achieving (A) ACR70, (B) CDAI REM and (C) SDAI REM. For tofacitinib 5 and 10 mg BID treatment groups, low levels of improvement in PROs, TJC, SJC and PGA are reported in patients who were not responsive to the first clinical outcome. ACR, American College of Rheumatology; BID, twice daily; CDAI, Clinical Disease Activity Index; HAQ-DI, Health Assessment Questionnaire-Disability Index; MTX, methotrexate; PGA, physician's global assessment; PROs, patient-reported outcomes; PtGA, patient global assessment; REM, remission; SDAI, Simplified Disease Activity Index; SJC, swollen joint count; TJC, tender joint count.
Figure 4
Figure 4
Venn diagram showing overlap of responses in patients treated with tofacitinib 5 mg BID and MTX for (A) CDAI LDA and ACR50; (B) CDAI REM and ACR70; (C) HAQ-DI <0.5 and ACR50; (D) HAQ-DI <0.5 and ACR70; (E) SDAI LDA and CDAI LDA and (F) SDAI REM and CDAI REM. The more the two circles of the Venn diagram overlap, the higher the concordance. Relative sizes of the Venn diagrams for tofacitinib 5 mg BID and MTX approximately reflect the smaller sample size of the MTX group. To be included in a Venn diagram, a patient must have non-missing values for both outcomes. The rows labelled Responders (N) represent the number of patients responsive for the first outcome, both outcomes and the second outcome, respectively. Rate (%), represents the overall response rate to the first outcome, both outcomes and the second outcome, respectively. The rows labelled From Venn diagrams (N) respresent the number of patients only responsive to the first outcome, both outcomes and only the second outcome, respectively; they sum to the number of patients who responded to at least one of the end points. Contribution (%) represents the proportional size of the contribution of the total number of patients who responded to only the first outcome, both outcomes and only the second outcome, respectively. ACR, American College of Rheumatology; BID, twice daily; CDAI, Clinical Disease Activity Index; HAQ-DI, Health Assessment Questionnaire-Disability Index; LDA, low disease activity; MTX, methotrexate; REM, remission; SDAI, Simplified Disease Activity Index.
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