Certolizumab Pegol Improves Patient-reported Outcomes in Rheumatoid Arthritis

May 16, 2011

RAPID-2 results show that certolizumab pegol plus methotrexate improves pain, physical function, and quality of life in patients with rheumatoid arthritis.

RAPID-2 trial results show that certolizumab pegol plus methotrexate improves pain, physical function, and quality of life in patients with rheumatoid arthritis.

A recent study shows that combination treatment with methotrexate and certolizumab pegol, a PEGylated anti-tumor necrosis factor, produced sustained improvement in physical function, pain, and other quality of life measures over one year in patients diagnosed with rheumatoid arthritis.

Researchers examined data from the Rheumatoid Arthritis PreventIon of structural Damage (RAPID) 2 trial to evaluate the impact of treatment with combination methotrexate and certolizumab pegol on patient-reported outcomes measures (PROs), the number needed to treat (NNT) based on those PROs, time to onset of response, and other clinical factors. NNT and other measures were determined in part by assessing improvement based on the concept of minimal clinically important differences (MCIDs). The researchers published their findings in the June issue of Annals of the Rheumatic Diseases.

For RAPID-2, patients diagnosed with rheumatoid arthritis who had not responded to treatment with methotrexate were randomized to receive placebo plus methotrexate for 24 weeks or certolizumab pegol (400 mg at weeks 0, 2 and 4 followed by certolizumab pegol 200 mg or 400 mg) plus methotrexate every two weeks. PROs assessed during the study included patient's pain, global assessment of disease activity, physical function, fatigue, and quality of life. Pain and disease activity were assessed using the 100 mm Visual Analogue Scales (MCID defined as 10 mm decreases from baseline). The authors used the Health Assessment Questionnaire-Disability Index to evaluate physical function (MCID is a 0.22-point decrease from baseline). They used the Fatigue Assessment Scale to evaluate treatment effect on fatigue level in patients (MCID is “10% of the scale range, corresponding to a 1-point decrease from baseline”). Quality of life was assessed using the Medical Outcomes Survey short-form 36-item (SF-36). Treatment efficacy was evaluated via the Disease Activity Score 28-joint count assessment-erythrocyte sedimentation rate.

Of 619 patients, 13% of the placebo group, 71% of the certolizumab pegol 200 mg group, and 74% of the certolizumab pegol 400 mg completed the study. Average patient age was 52 years, 82% of the cohort was female, with average disease duration of more than six years. This patient group also had “markedly lower SF-36 domain scores compared with a US normative population without arthritis.”

The authors reported that treatment with certolizumab pegol was associated with “statistically significant and clinically meaningful” improvements in pain, disease activity, fatigue, and physical function as early as week 1. Patients treated with certolizumab pegol also reported significant improvements in overall quality of life compared to placebo at week 12. Improvements in pain, disease activity, physical function, fatigue, and quality of life were maintained until the end of the study after week 24. At week 24, “significantly more patients in the [certolizumab pegol] plus [methotrexate] groups reported improvements ≥MCID in all six PROs.”

At week 24, 63% of certolizumab pegol 200 mg plus methotrexate patients reported “clinically meaningful improvements in one or more PRO compared with 13% in placebo.” Approximately 23% certolizumab pegol plus methotrexate-treated patients reported “clinically meaningful improvements (≥MCID) in all six PROs compared with 3% in placebo.”

The NNT to achieve “simultaneous clinically meaningful improvements in one, two, three or four of six PROs was approximately two additional patients;” NNT to achieve improvements in five of six PROs was three. NNT for all six PROs was five patients.

These data provide support for “the use of all PRO measures including individual SF-36 domains to fully assess treatment benefit. SF-36 assesses eight domains: Physical Functioning (PF), Role Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE) and Mental Health (MH). Physical function scores were correlated with SF-36 PF, PCS, and BP scores. These and other correlations suggest that “treatment-associated changes across all PROs is thus a better method for assessing change in multidimensional function.” The authors also advised that “evaluation of all SF-36 domain scores offers more information than the summary scores alone.” Thus physicians should “consider data from all SF-36 domains as well as [Physical and Mental Component Summary] scores in their decision-making process.”

These results “indicate that early improvement in PROs predict both clinical and PROs at 6 months,” and suggest that patients treated with [certolizumab pegol] who achieve early responses according to either PROs or disease activity measure “have a greater chance of avoiding long-term disability.” The authors concluded that treatment with methotrexate plus certolizumab pegol “provides broad relief from the multiple burdens of RA. Significant and clinically meaningful improvements, low NNTs and increased likelihood of achieving longer term outcomes with an earlier PRO response indicate that [certolizumab pegol] is an effective treatment option, offering substantial benefits to patients.”