Clinical trial NCT01808118: Continuing Versus Withdrawing Adalimumab in Maintaining Remission in Non-Radiographic Axial Spondyloarthritis
Official title: A Multicenter, Randomized, Double-Blind, Study Comparing the Efficacy and Safety of Continuing Versus Withdrawing Adalimumab Therapy in Maintaining Remission in Subjects With Non-Radiographic Axial Spondyloarthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Keywords: Spondylitis
Spondylarthropathy
Ankylosing Spondyloarthritis
Spondyloarthritis
Spinal Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Adalimumab
Antirheumatic Agents
Anti-Inflammatory Agents
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2013-03-11
Enrollment: 673
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this multicenter, randomized, double-blind study was to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week SC in maintaining remission in subjects with moderate to severe non-radiographic axial spondyloarthritis.

Detailed description: The study duration included a 42-day Screening Period, a 28-week open-label 40 mg adalimumab every other week (eow) treatment period (Period 1), a 40-week double-blind placebo controlled eow treatment period (Period 2) with an opportunity to receive at least 12 weeks of rescue therapy with open-label adalimumab (participants that flared at Weeks 60, 64 or 68 were allowed 12 weeks of rescue therapy and final visits were at Weeks 72, 76 or 80 respectively), plus a 70-day follow-up phone call. Participants in sustained Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were randomized at Week 28 at a 1:1 ratio to receive either blinded adalimumab 40 mg eow or matching placebo. The length of exposure to adalimumab depended on remission or flare status and ranged from 20 (first time Ankylosing Spondylitis Disease Activity Score \[ASDAS\] remission was calculated) to 80 weeks of treatment.

Eligibility criteria: Inclusion Criteria:

* Adult participants with inadequate response to ≥2 nonsteroidal anti-inflammatory drugs (NSAIDs)
* Participants with non-radiographic axial spondyloarthritis fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axial SpA classification criteria, but not fulfilling the radiologic criterion of the modified New York criteria for ankylosing spondylitis
* Participants must have baseline disease activity as defined by having an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.100, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and Patient's Assessment of Total Back Pain score ≥ 4 based on a Numeric Rating Scale (NRS) at both the screening and baseline visits
* Participants with evidence of active inflammation in the sacroiliac (SI) joints or spine on MRI, or elevated high sensitivity C-reactive protein (hs-CRP) at screening
* Negative tuberculosis (TB) screening assessment
* Ability to administer subcutaneous injections or have a qualified person available to administer injections
* If female, either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug.
* Participant judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray, and a 12-lead electrocardiogram performed at screening

Exclusion Criteria:

* Prior anti-Tumor Necrosis Factor (TNF) therapy; biologic therapy with a potential therapeutic impact on SpA or treated with an investigational drug of chemical or biologic nature within 30 days or 5 half-lives prior to the baseline visit.
* Fulfillment of the radiologic criterion of the modified New York criteria for Ankylosing Spondylitis at or prior to the screening visit
* Recent infection requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the baseline visit or oral anti-infectives within 14 days prior to the baseline visit
* Significant medical events or conditions that may put participants at risk for participation
* Female participants who are pregnant or breast-feeding or considering becoming pregnant during the study
* Known hypersensitivity to adalimumab or its excipients as stated in the label

Primary outcomes:
measure: Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
timeFrame: From Week 28 through 68
Secondary outcomes:
measure: Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Rescue Therapy Week 12
measure: Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Rescue Therapy Week 12
measure: Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy
timeFrame: Baseline and Rescue Therapy Week 12
measure: Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68
timeFrame: Weeks 28 and 68
measure: Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68
timeFrame: Baseline, Weeks 28 and 68
measure: Time to Flare at Week 68
timeFrame: From Week 28 through 68
measure: Time to Partial Flare at Week 68
timeFrame: From Week 28 through 68
measure: Number of Participants Reaching Flare Definition by Week 68
timeFrame: From Week 28 through 68
measure: Number of Participants Reaching Partial Flare Definition by Week 68
timeFrame: From Week 28 through 68
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: Landewe R, Sieper J, Mease P, Inman RD, Lambert RG, Deodhar A, Marzo-Ortega H, Magrey M, Kiltz U, Wang X, Li M, Zhong S, Mostafa NM, Lertratanakul A, Pangan AL, Anderson JK. Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 2018 Jul 14;392(10142):134-144. doi: 10.1016/S0140-6736(18)31362-X. Epub 2018 Jun 29.