Tofacitinib or adalimumab versus placebo: patient-reported outcomes from OPAL Broaden-a phase III study of active psoriatic arthritis in patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs

Abstract

Objectives: Tofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). We evaluated patient-reported outcomes (PROs) in patients with PsA refractory to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR) and tumour necrosis factor inhibitor-naïve in a 12-month, phase III randomised controlled trial (OPAL Broaden [NCT01877668]).

Methods: Patients (N=422) received tofacitinib 5 mg or 10 mg twice daily, adalimumab 40 mg subcutaneously every 2 weeks or placebo advancing to tofacitinib 5 mg or 10 mg twice daily at month 3. Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences (MCID); and scores ≥normative values in: Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level questionnaire (EQ-5D-3L) and Ankylosing Spondylitis Quality of Life (ASQoL) were determined. Nominal p values were cited without multiple comparison adjustments.

Results: At month 3, PtGA, Pain, PGJS, FACIT-Fatigue, EQ-5D-3L, ASQoL and SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP) and vitality domain scores exceeded placebo with both tofacitinib doses (p≤0.05); SF-36v2 social functioning with 5 mg twice daily (p≤0.05). Percentages reporting improvements ≥MCID in PtGA, Pain, PGJS, FACIT-Fatigue, ASQoL and SF-36v2 PCS, PF, BP and general health scores exceeded placebo with both tofacitinib doses (p≤0.05) and were similar with adalimumab.

Conclusion: csDMARD-IR patients with active PsA reported statistically and clinically meaningful improvements in PROs with tofacitinib compared with placebo at Month 3.

Keywords: DMARDs (synthetic); outcomes research; patient perspective; psoriatic arthritis; treatment.

Figure 1

Least squares mean (LSM) changes from baseline: (A) Patient Global Assessment of disease activity visual analogue scale (PtGA-VAS) (mm); (B) Pain-VAS (mm); (C) Patient Global Joint and Skin Assessment (PGJS)-VAS (mm) arthritis and psoriasis. *p≤0.05, **p<0.01, ***p<0.001 compared with placebo; results up to month 3 were based on a repeated-measures model including data up to month 3 for tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneous injection once every 2 weeks and combined placebo group. Results after month 3 were based on a second repeated-measures model including data up to end of study for the five treatment sequences (tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneous injection once every 2 weeks, placebo → tofacitinib 5 mg twice daily and placebo → tofacitinib 10 mg twice daily), reporting results after month 3 only. Missing values were not imputed. Patient N is number of subjects evaluable at each visit. BID, twice daily; SC Q2W, subcutaneous injection once every 2 weeks.

Figure 2

Percentages of patients reporting improvements from baseline ≥minimum clinically important difference (MCID) and number needed to treat (NNT) in (A) patient-reported outcomes (PROs); (B) Short Form-36 health survey version 2 (SF-36v2) domain scores at month 3 and percentages of patients reporting scores ≥normative values in (C) PROs; (D) SF-36v2 domain scores, at baseline and month 3. *p≤0.05, **p<0.01, ***p<0.001 compared with placebo; p values were based on the normal approximation for the difference in binomial percentages without imputation for missing values (except Health Assessment Questionnaire Disability Index [HAQ-DI] MCID response, which used non-responder imputation); N is the number of patients per group in the Full Analysis Set; the number of patients evaluable for each PRO endpoint may be fewer than N; MCID cut-offs: Patient Global Assessment of disease activity visual analogue scale (PtGA-VAS) decrease from baseline ≥10 mm; Pain-VAS decrease from baseline ≥10 mm; Patient Global Joint and Skin Assessment (PGJS)-VAS decrease from baseline ≥10 mm; SF-36v2: Physical Component Summary (PCS) and Mental Component Summary (MCS) increase from baseline ≥2.5, SF-36v2 domain scores increase from baseline ≥5.0; Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) increase from baseline ≥4.0; Ankylosing Spondylitis Quality of Life (ASQoL) decrease from baseline ≥1.8; HAQ-DI decrease from baseline ≥0.35; MCIDs are defined here in terms of mean change from baseline to month 3 in a treatment group; NNT calculated by the inverse of the percentage of patients receiving active treatments reporting improvements ≥MCIDs minus the percentage of patients in the placebo group reporting improvements ≥MCIDs; the percentage of patients reporting scores ≥normative values: HAQ-DI ≤0.25, FACIT-Fatigue Total score ≥40.1, SF-36v2 each of the component summary and domain scores ≥50. BID, twice daily; BP, bodily pain; GH, general health; MH, mental health; NA, not available; PF, physical functioning; RE, role emotional; RP, role physical; SC Q2W, subcutaneous injection once every 2 weeks; SF, social functioning; VT, vitality.

Figure 3

(A) Least squares mean (LSM) change from baseline in Short Form-36 health survey version 2 (SF-36v2) Physical Component Summary (PCS) score; and (B) spydergram of domain scores from baseline to month 3 and versus age-matched and gender-matched norms. Panel A: *p≤0.05, **p<0.01, ***p<0.001 compared with placebo; results up to month 3 were based on a repeated measures model including data (norm-based) up to month 3 for tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneous injection once every 2 weeks and combined placebo group. Results after month 3 were based on a second repeated measures model including data up to end of study for the five treatment sequences (tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneous injection once every 2 weeks, placebo → tofacitinib 5 mg twice daily and placebo → tofacitinib 10 mg twice daily), reporting results after month 3 only. Missing values were not imputed. Dashed line indicates end of placebo-controlled period. N represents the number of subjects evaluable at each visit. Panel B: *p≤0.05, **p<0.01, ***p<0.001 compared with placebo; spydergrams were generated using domain raw scores (range 0–100); US age–gender norms were matched to the protocol population; spydergrams are for illustrative purposes only; p values were generated using a repeated measures model for comparisons with placebo based on LSM changes from baseline in domain norm-based scores at month 3 (table 1). Missing values were not imputed. BID, twice daily; BP, bodily pain; GH, general health; MH, mental health; PF, physical functioning; RE, role emotional; RP, role physical; SC Q2W, subcutaneous injection once every 2 weeks; SF, social functioning; VT, vitality.

Figure 4

Least squares mean (LSM) changes from baseline in (A) Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Total score and (B) Ankylosing Spondylitis Quality of Life (ASQoL). *p≤0.05, **p<0.01, ***p<0.001 compared with placebo; results up to month 3 were based on a repeated measures model including data up to month 3 for tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneous injection once every 2 weeks and combined placebo group. Results after month 3 were based on a second repeated measures model including data up to end of study for the five treatment sequences (tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, adalimumab 40 mg subcutaneous injection once every 2 weeks, placebo → tofacitinib 5 mg twice daily and placebo → tofacitinib 10 mg twice daily), reporting results after month 3 only. Missing values were not imputed. N is the number of subjects evaluable at each visit. BID, twice daily; SC Q2W, subcutaneous injection once every 2 weeks.