Continuing Versus Withdrawing Adalimumab in Maintaining Remission in Non-Radiographic Axial Spondyloarthritis

AbbVie

Status and phase: Completed; Phase 3

Conditions: Axial Spondyloarthritis

Treatments: Biological: adalimumab; Biological: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01808118

M13-375

2012-000646-35 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 673 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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673 participants in 3 patient groups, including a placebo group

Double-Blind Adalimumab

Experimental group

Description:

40 mg every other week (eow), Weeks 28-68. Blinded adalimumab was discontinued in participants who met the criteria for flare.

Treatment:

Biological: adalimumab

Open-label (OL) Adalimumab

Experimental group

Description:

40 mg every other week (eow), Weeks 0-28. If participants flared during the double-blind period, they had an opportunity to receive at least 12 weeks of open-label adalimumab 40 mg eow.

Treatment:

Biological: adalimumab

Placebo

Placebo Comparator group

Description:

Placebo every other week (eow), Weeks 28-68. Placebo was discontinued in participants who met the criteria for flare.

Treatment:

Biological: Placebo