Trial Outcomes & Findings for The Incidence of Extra-Articular Manifestations in Participants With Ankylosing Spondylitis Treated With Golimumab (MK-8259-012) (NCT NCT01668004)

Last Updated: 2019-02-04

Results Overview

Uveitis is an extra-articular manifestation of ankylosing spondylitis (AS) involving inflammation of the eye. The occurrence rate (assessed as present/absent) of uveitis attacks was determined over two 1-year long periods regardless of whether the event started during the assessed year: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

101 participants

Primary outcome timeframe

Twelve Months Prior to Enrollment to Study Month 12

Results posted on

2019-02-04

Participant Flow

A total of 104 participants were screened; 3 participants were screen failures who did not enroll.

Participant milestones

Participant milestones
Measure	GLM 50 mg Golimumab (GLM) given subcutaneously at a dose of 50 mg once monthly for up to 12 months
Overall Study STARTED	101
Overall Study Treated	101
Overall Study COMPLETED	76
Overall Study NOT COMPLETED	25

Reasons for withdrawal

Reasons for withdrawal
Measure	GLM 50 mg Golimumab (GLM) given subcutaneously at a dose of 50 mg once monthly for up to 12 months
Overall Study Adverse Event	7
Overall Study Withdrawal by Subject	2
Overall Study Lost to Follow-up	5
Overall Study Lack of Efficacy	9
Overall Study Non-compliance with treatment	2

Baseline Characteristics

The Incidence of Extra-Articular Manifestations in Participants With Ankylosing Spondylitis Treated With Golimumab (MK-8259-012)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GLM 50 mg n=101 Participants GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months
Age, Continuous	44.4 years STANDARD_DEVIATION 12.9 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants
Time since diagnosis	10.8 Years STANDARD_DEVIATION 11.8 • n=5 Participants
Age at onset of disease	33.1 Years STANDARD_DEVIATION 11.8 • n=5 Participants
Height	175.82 cm STANDARD_DEVIATION 9.62 • n=5 Participants
Weight	82.63 kg STANDARD_DEVIATION 18.00 • n=5 Participants
Abdominal circumference	95.5 cm STANDARD_DEVIATION 15.5 • n=5 Participants

PRIMARY outcome

Timeframe: Twelve Months Prior to Enrollment to Study Month 12

Population: All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (occurence of uveitis).

Outcome measures

Outcome measures
Measure	Before Initial Anti-TNF/GLM Treatment n=93 Participants Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).	After GLM Treatment Start n=93 Participants GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months
Occurence Rate of Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment	0.08 Ratio	0.08 Ratio

PRIMARY outcome

Timeframe: Twelve Months Prior to Enrollment to Study Month 12

Population: All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (incidence of uveitis). One participant for whom the timing of uveitis events could not be determined was excluded from the analysis.

Uveitis is an extra-articular manifestation of AS involving inflammation of the eye. The annual incidence rate of new uveitis attacks was determined over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose. All participants were counted as contributing a full year of GLM exposure even if discontinuing early. Due to ongoing uveitis cases at time of period entry, participants did not have the same risk of new events during the one year periods. Participants with ongoing uveitis at start of GLM who had the adverse event for the entire treatment period were counted as having the 'new attack' before and no "new attack" after GLM treatment start.

Outcome measures

Outcome measures
Measure	Before Initial Anti-TNF/GLM Treatment n=92 Participants Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).	After GLM Treatment Start n=92 Participants GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months
Annual Incidence Rate of New Uveitis Attacks in Participants Before Anti-TNF/GLM Treatment and After the Start of GLM Treatment	9.8 Events per 100 participant years	2.2 Events per 100 participant years

SECONDARY outcome

Timeframe: Twelve Months Prior to Enrollment to Study Month 12

Population: The incidence rates for new onset or flares of IBD and psoriasis could not be evaluated due to limitations of the data collected; occurrence of flares was not collected (specifically, history of IBD and/or psoriasis could not be distinguished from flares of IBD and/or psoriasis) and, therefore, results could not be determined.

IBD (Crohn's disease or ulcerative colitis) and psoriaris are extra-articular manifestations of AS involving the intestinal tract and skin, respectively. The annual incidence rates of new-onset or flares of IBD and psoriasis were to be determined separately (i.e., for each condition) over two 1-year long periods: 1) the historical observation period consisting of the year before initial anti-TNF treatment (for anti-TNF experienced participants) or prior to first GLM dose (for anti-TNF naïve participants); and 2) the GLM observation period consisting of the year after first GLM dose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (BL), Study Month 3

Population: All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (BASDAI 50).

The percentage of participants with a BASDAI 50 response (defined as a 50% improvement or as an absolute improvement of 2 points in their BASDAI physical function score) at three months was determined. The BASDAI consists of total of six visual analog scales (VAS): five VAS (0 to 10 cm; increasing severity) measuring severity of fatigue, spinal pain, peripheral joint pain or swelling, localized tenderness, and severity of morning stiffness and one VAS (0 to 10 cm; increasing duration up to 2 hours) measuring duration of morning stiffness. The morning stiffness scores are averaged and summed with the scores for the remaining four items resulting in a composite score (0-50); the final BASDAI score (0-10) is derived by dividing by 5.

Outcome measures

Outcome measures
Measure	Before Initial Anti-TNF/GLM Treatment n=88 Participants Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).	After GLM Treatment Start GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months
Percentage of Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI 50) Responders Following Treatment With GLM	33.0 Percentage of participants	—

SECONDARY outcome

Timeframe: BL, Study Month 3

Population: All participants who received at least 3 months of GLM in the study and at least 3 months of follow-up data available for analysis of the endpoint (ASDAS).

The percentage of participants with ASDAS clinically important improvement (ASDAS-CII; ≥ 1.1 units) and major improvement (ASDAS-MI; ≥ 2.0 units) at 3 months were determined. The ASDAS incorporates three items from the BASDAI (spinal pain, duration of morning stiffness, and peripheral joint pain or swelling) each assessed on a VAS (0 to 10 cm; increasing severity) as well as patient global assessment of disease activity (VAS; 0 to 10 cm; increasing severity) and a laboratory measure of inflammation (CRP level \[mg/L\] or ESR \[mm/hr\]). ASDAS was calculated using the formula: 0.12\*Spinal Pain + 0.06\*Duration of Morning Stiffness + 0.11\*Patient Global + 0.07\*Peripheral Pain/Swelling + 0.58\*ln(CRP (mg/L) +1). A decrease in ASDAS at 3 months relative to BL signifies an improvement in physical function; ASDAS-MI (≥ 2.0 units decrease from BL) signifies a comparatively greater improvement in physical function than ASDAS-CII (≥ 1.1 units decrease from BL).

Outcome measures

Outcome measures
Measure	Before Initial Anti-TNF/GLM Treatment n=84 Participants Historical observation period: Retrospective record review over the 12 months prior to the initial anti-TNF treatment (anti-TNF experienced participants) or the first GLM dose (anti-TNF naïve participants).	After GLM Treatment Start GLM observation period: Prospective follow-up of participants given GLM subcutaneously at a dose of 50 mg once monthly for up to 12 months
Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM ASDAS-CII (≥ 1.1 units)	40.5 Percentage of participants	—
Percentage of Ankylosing Spondylitis Disease Activity Score (ASDAS) Responders Following Treatment With GLM ASDAS-MI (≥ 2.0 units)	19.0 Percentage of participants	—

Adverse Events

GLM 50 mg

Serious events: 7 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GLM 50 mg n=101 participants at risk GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months
Cardiac disorders Acute Coronary Syndrome	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Cardiac disorders Cardiac Failure	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Gastrointestinal disorders Colitis Ulcerative	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Gastrointestinal disorders Large Intestinal Ulcer Haemorrhage	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Infections and infestations Cellulitis	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Infections and infestations Pneumonia	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Infections and infestations Urinary Tract Infection	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Musculoskeletal and connective tissue disorders Bursitis	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Surgical and medical procedures Fistula Repair	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Vascular disorders Hypovolaemic shock	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Infections and infestations Infection	0.99% 1/101 • Number of events 1 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.

Other adverse events

Other adverse events
Measure	GLM 50 mg n=101 participants at risk GLM given subcutaneously at a dose of 50 mg once monthly for up to 12 months
Infections and infestations Nasopharyngitis	10.9% 11/101 • Number of events 12 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.
Nervous system disorders Headache	12.9% 13/101 • Number of events 19 • Up to one year All safety analyses were performed on the All Treated Set, defined as all patients who received at least one dose of golimumab in the study. Only safety data during the GLM period was collected.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study. The sponsor shall have the right to review and comment with respect to publications, abstracts, slides, and manuscripts and the right to review and comment on the data analysis and presentation with regard to proprietary information, accuracy of information, and regulatory compliance.
Publication restrictions are in place

Restriction type: OTHER