Long-Term Radiographic and Patient-Reported Outcomes in Patients with Rheumatoid Arthritis Treated with Tofacitinib: ORAL Start and ORAL Scan Post-hoc Analyses

Abstract

Introduction: Here we examine the relationship between achieving different levels of disease activity with tofacitinib (an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis), long-term structural progression, and patient-reported physical function.

Methods: This was a post hoc analysis of two 24-month, phase III randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder (IR) patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily as either monotherapy or with background MTX. The modified total Sharp score (mTSS) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were analyzed at month 24 according to disease activity at month 6 defined by the Clinical Disease Activity Index (CDAI) or the Disease Activity Score in 28 joints, C-reactive protein (DAS28CRP).

Results: Mean changes from baseline in mTSS at month 24 were less in patients with CDAI remission at month 6 than in those with CDAI moderate/high disease activity (MDA/HDA) at month 6. A DAS28CRP of < 1.9 most closely approximated CDAI remission (≤ 2.8). Tofacitinib appeared to inhibit joint damage in the presence of persistent inflammation compared with MTX. More patients receiving tofacitinib or MTX with CDAI remission or low disease activity (LDA) at month 6 reported normative HAQ-DI scores (< 0.5) at month 24 than did those with CDAI MDA/HDA.

Conclusion: Regardless of treatment, in both MTX-naïve and MTX-IR patients, remission or LDA at month 6 was associated with successful long-term outcomes: inhibition of structural progression and normative HAQ-DI scores. Long-term outcomes were similar when patients achieved CDAI remission or a DAS28CRP of < 1.9, confirming that this is an appropriate cut-off for remission with DAS28CRP. Tofacitinib potentially inhibits joint damage even with persistent inflammation.

Funding: Pfizer Inc.

Trial registration: Clinicaltrials.gov identifiers: NCT01039688 and NCT00847613.

Keywords: Disease activity; HAQ-DI; Janus kinase inhibitor; Radiographic outcomes; Rheumatoid arthritis; Tofacitinib.

Figures

Fig. 1

Mean change from baseline in van der Heijde mTSS at month 24 according to response at month 6 defined by CDAI (a) and CDAI remission, a DAS28CRP of < 1.9, and DAS28CRP of < 2.6 (b). BID twice daily, CDAI Clinical Disease Activity Index, CI confidence interval, DAS28CRP Disease Activity Score in 28 joints, C-reactive protein, IR inadequate responder, LDA low disease activity, MDA/HDA moderate/high disease activity, mTSS modified total Sharp score, MTX methotrexate

Fig. 2

Proportion of radiographic non-progressors at month 24 according to disease activity at month 6 defined by CDAI (a) and CDAI remission, DAS28CRP < 1.9, and DAS28CRP < 2.6 (b). Radiographic non-progression is defined as a change in mTSS of ≤ 0.0. BID twice daily, CDAI Clinical Disease Activity Index, CI confidence interval, DAS28CRP Disease Activity Score in 28 joints, C-reactive protein, IR inadequate responder, LDA low disease activity, MDA/HDA moderate/high disease activity, mTSS modified total Sharp score, MTX methotrexate

Fig. 3

Proportion of patients reporting normative HAQ-DI scores (a) and CDAI remission, DAS28CRP < 1.9, and DAS28CRP < 2.6 (b). Normative HAQ-DI was defined as a score of < 0.5. BID twice daily, CDAI Clinical Disease Activity Index, CI confidence interval, DAS28CRP Disease Activity Score in 28 joints, C-reactive protein, HAQ-DI Health Assessment Questionnaire-Disability Index, IR inadequate responder, LDA low disease activity, MDA/HDA moderate/high disease activity, MTX methotrexate

Fig. 4

Mean change from baseline at month 24 in HAQ-DI score according to disease activity at month 6 defined by CDAI (a) and CDAI remission, DAS28CRP < 1.9, and DAS28CRP < 2.6 (b). BID twice daily, CDAI Clinical Disease Activity Index, CI confidence interval, DAS28CRP Disease Activity Score in 28 joints, C-reactive protein, HAQ-DI Health Assessment Questionnaire-Disability Index, IR inadequate responder, LDA low disease activity, MDA/HDA moderate/high disease activity, MTX methotrexate