Secukinumab improves patient-reported outcomes across all doses in psoriatic arthritis
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Secukinumab provides early, clinically meaningful, statistically significant and sustained improvements in patient-reported outcomes across all doses, compared with placebo, in active psoriatic arthritis, according to data.
“Secukinumab was effective in both TNF-naïve and TNF-inadequate-response patients with PsA, offering significant and clinically meaningful improvements in patient-reported outcomes,” Vibeke Strand, MD, MACR, FACP, of Stanford University, in Palo Alto, California, told Healio.
According to Strand and colleagues, multiple previous randomized trials have demonstrated the efficacy of secukinumab (Cosentyx, Novartis) in improving disease activity across “all clinical manifestations of psoriatic arthritis, including patient reported outcome (PRO) measures of pain, fatigue, physical function, and HRQOL.” However, improvements reported by patients with PsA who receive secukinumab as a first-line or later-line biologic have not been rigorously evaluated, they wrote.
“The phase 3 FUTURE 5 randomized trial evaluated the efficacy of secukinumab 300 mg or 150 mg with or without a loading dose compared with placebo for the treatment of patients with active psoriatic arthritis,” the researchers added. “Secukinumab treatment led to significantly better improvements in clinical symptoms and physical function at 16 weeks and reduction in radiographical progression at 24 weeks compared with placebo;14 these effects were sustained to week 104.”
To examine the impact of secukinumab on patient-reported outcomes in active PsA, Strand and colleagues conducted a post hoc analysis of the phase 3 FUTURE 5 trial. In that study, 996 adults with symptoms of moderate-to-severe PsA for at least 6 months were randomly assigned to receive one of three secukinumab regimens — 300 mg, 150 mg or 150 mg with no loading dose — or placebo weekly from baseline to week 4, and every 4 weeks thereafter. In all, 222 received 300 mg, 220 received 150 mg and 22 received 150 mg with no loading dose, while 332 were assigned to placebo.
Prespecified patient-reported outcomes included patient global assessments (PtGA) of disease activity, psoriasis and arthritis visual analogue scale (VAS) scores, pain VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), 36-item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), and quality of life questionnaires. For this study, the researchers reported mean changes from baseline and the proportion of patients reporting improvements equal to, or more than, the minimum clinically important differences (MCIDs), as well as scores equal to, or more than, the normative values.
In addition, the researchers stratified and analyzed participants by their TNF-inhibitor status — either as naïve or an inadequate responder. Among the intention-to-treat population, 697 participants were naïve while 299 inadequate responders.
According to the researchers, who published their findings in The Lancet Rheumatology, participants in all secukinumab groups reported significant least-squares mean changes, compared with placebo, at week 16 for all outcomes save for the SF-36 mental component summary (MCS), regardless of TNF-inhibitor use.
These included PtGA in the 300 mg (difference versus placebo = –12.2; 95% CI, –16.3 to –8.1), 150 mg (–8.22; 95% CI, –12.4 to –4.1) and 150 mg with no loading dose (–8.3; 95% CI, –12.5 to –4.2) groups; pain VAS in the 300 mg (–14.3; 95% CI, –18.3 to –10.2), 150 mg (–11.5; 95% CI, –15.6 to –7.5) and 150 mg with no loading dose (–11.3; 95% CI, –15.3 to –7.2) groups; HAQ-DI in the 300 mg (–0.33; 95% CI, –0.42 to –0.24), 150 mg (–0.23; 95% CI, –0.32 to –0.14) and 150 mg with no loading dose (–0.24; 95% CI, –0.33 to –0.15) groups; and FACIT-F in the 300 mg (4.8; 95% CI, 3.2-6.4), 150 mg (4.2; 95% CI, 2.6-5.8) and 150 mg with no loading dose (3.5; 95% CI, 1.9-5.1) groups.
Additionally, the proportion of patients with improvements equal to, or better than, MCID at week 16 was higher among those treated with secukinumab, compared with the placebo group, for most outcomes except SF-36 (MCS), regardless of TNF inhibitor use.
“There were improvements in multiple PROs, including HRQOL, HAQ, Pain PtGA and fatigue except SF-36 MCS, which was high at baseline,” Strand said. “Improvements were statistically significant for secukinumab at all doses. There were rapid and sustained responses to year 2.
“Interpreting the clinical meaningfulness in terms of improvements equal to or better than MCID, and scores that met or exceeded normative values, there were more among TNF-naïve patients than in those with inadequate response,” she added. “The magnitudes of improvement were similar between patients who were TNF-naïve and inadequate responders, although baseline scores lower in inadequate responders, and placebo responses were less than in the TNF-naïve.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Quality of life (QOL) measurement was a hot area of research in the mid-1990s and patient-reported outcomes (PRO) later became a focus of the FDA and the pharmaceutical industry in the 2000s. The FDA defines a PRO as any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else.
PROs are particularly important in oncology where the risk-benefit analysis of a chemotherapy may find a treatment that extends life but has unfavorable toxicity and QOL measures from the patient’s standpoint.
The present analysis reviewed the seven questionnaires from the phase 3 FUTURE 5 trial, used to ascertain PROs with secukinumab in psoriatic arthritis. The PROs were almost universally significantly improved, even for those patients with prior TNF-inhibitor treatment.
In our own practice, I find asking the patient the Health Assessment Questionnaire (HAQ) often gives me a better insight into the burden of disease that the patient is experiencing. Ted Pincus used to say that rheumatologists would see an RA patient and, without any standardized measurement, would note “doing well” as their disease progressed. PROs are a way to see the disease from the patient’s standpoint and it is helpful to use these in clinical practice, and they are now being used in clinical trials.
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