RA Outcomes with Tocilizumab Surpass Those of Adalimumab, Methotrexate
Benefits reflected in both physical and mental scores
Judy George,September 25, 2017 MedPage
Tocilizumab (Actemra) monotherapy showed more clinically meaningful patient-reported outcomes in patients with active rheumatoid arthritis (RA) than monotherapy with either methotrexate or adalimumab (Humira), although patients reported improvement with all three drugs, a post-hoc analysis of the AMBITION (Actemra versus Methotrexate Double-blind Investigative Trial in Monotherapy) and ADACTA (Tocilizumab Monotherapy versus Adalimumab Monotherapy for Treatment of Rheumatoid Arthritis) trials found.
At 24 weeks, AMBITION patients treated with tocilizumab monotherapy said they had significantly greater mean improvements than methotrexate-treated patients in the following:
- Health Assessment Questionnaire-Disability Index (HAQ-DI) scores (-0.7 versus -0.5)
- Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (8.7 versus 5.7)
- Short Form (SF)-36 physical component scores (9.8 versus 7.8)
Tocilizumab-treated ADACTA patients reported significantly greater improvements at week 24 than those treated with adalimumab monotherapy in:
- Patient global assessment (PtGA) scores (-42.3 versus -31.8)
- Pain (-40.1 versus -28.7)
- SF-36 mental component scores (7.9 versus 5.0)
Tocilizumab also resulted in more RA patients reporting outcomes at or above normative values, according to the study by Graeme Jones, MD, of the University of Tasmania in Australia, and colleagues, writing online in RMD Open: Rheumatic & Musculoskeletal Diseases.
"Although patients receiving methotrexate or adalimumab reported improvements across all patient-reported outcomes, tocilizumab-treated patients reported equivalent or greater improvements. Overall, tocilizumab was more effective at 24 weeks than methotrexate in patients without prior inadequate responses to methotrexate or tumor necrosis factor inhibitors and was more effective as a first-line biologic than adalimumab in patients for whom continued treatment with methotrexate was inappropriate."
Few trials have examined the effect of tocilizumab monotherapy on patient-reported outcomes in RA patients, the team noted, and most available data is limited to the patient-reported outcomes included in the American College of Rheumatology (ACR) core set of PtGA, pain, and HAQ-DI.
"Beyond improvement in the ACR core set components, patients have expressed the importance of alleviating disruptions to work productivity, social functioning, fatigue, and the negative mental and emotional effects from this disease," the investigators wrote. "By evaluating the impact of tocilizumab on improvement of fatigue and physical, social, and mental/emotional well-being measures encompassed in the SF-36, the present study substantially expands the understanding of the efficacy of tocilizumab improving patient-reported outcomes and patients' health-related quality of life (HRQOL)."
Jones and colleagues studied data from two clinical trials of tocilizumab, a monoclonal antibody that inhibits the interleukin-6 receptor and is approved to treat patients with moderate to severe RA. AMBITION was a phase III multicenter trial that compared tocilizumab monotherapy (n=265) with methotrexate monotherapy (n=259) in moderate to severely active RA. ADACTA was a phase IV multicenter trial that compared tocilizumab monotherapy (n=163) and adalimumab monotherapy (n=162) in patients with severe RA.
In the methotrexate and tocilizumab arms of AMBITION, 81% and 83% of patients were women, and 73% and 71% were white, respectively. The average age was approximately 51, and the mean baseline clinical disease activity index (CDAI) was 43.2 in both groups. In the adalimumab and tocilizumab arms of ADACTA, 82% and 79% were women, 82% and 89% were white, and the mean baseline CDAI was 43.1 and 40.8, respectively; average age was about 54.
HRQOL was assessed at baseline and at 24 weeks in each study population. Study outcomes included mean changes from baseline in patient-reported outcomes, the proportion of patients who reported improvements that equaled or exceeded minimum clinically important differences for each outcome, and the proportion of patients who reported scores that were at or above age- and sex-matched normative values.
Patients who received tocilizumab monotherapy in both AMBITION and ADACTA reported greater improvements across all patient-related outcomes from baseline to 24 weeks. Patients also reported higher mean scores across all SF-36 domains, more closely approaching normative values for age and sex and indicative of clinically meaningful improvements. Consistent with these findings, tocilizumab-treated patients in both trials experienced greater improvements in CDAI from baseline to 24 weeks, the team reported.
In the AMBITION cohort, significantly more tocilizumab patients equaled or exceeded minimally clinically important differences in HAQ-DI (number needed to treat [NNT] 11.0), FACIT-Fatigue (NNT 7.8), and SF-36 domain scores including vitality (NNT 14.5). In ADACTA, a significantly higher proportion of tocilizumab patients reported clinically meaningful improvements in pain (NNT 7.5), SF-36 mental component (NNT 6.4), and the SF-36 vitality domain (NNT 6.0) scores.
Higher proportions of patients in all treatment groups reported scores greater than or equal to age- and sex-matched normative values at 24 weeks, indicating clinically important improvements. In AMBITION, 24% to 44% of tocilizumab patients reported scores equal to or above normative values across HAQ-DI, FACIT-Fatigue, and physical and mental components of SF-36. In ADACTA, 22% to 49% of tocilizumab patients reported scores at or above normative values for HAQ-DI, FACIT-Fatigue, and SF-36 physical and mental components.
"These data indicate that achievement of normative patient-reported outcome scores that more closely match those reported by healthy populations is an attainable goal for treatment of RA, regardless of therapy," the authors wrote.
One limitation of the study was the use of adalimumab monotherapy in ADACTA, the researchers said, explaining that while tocilizumab has similar efficacy either as monotherapy or when combined with methotrexate, adalimumab in combination with methotrexate is more effective than adalimumab alone. In addition, patient outcomes were measured for only 24 weeks, and data from these trials also might be skewed by patients' anticipation of improvement with a new therapy.
This study was funded by F. Hoffmann-La Roche Ltd/Genentech, Inc.
Jones and co-authors reported financial relationships with AbbVie, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celltrion, Crescendo Bioscience, F. Hoffmann-La Roche Ltd/Genentech, Inc., GSK, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, UCB, AB2 Bio, Actelion, Debiopharm, MSD, and BMS.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner