A Study to Assess Immune Response Following Zoster Vaccination to Subjects With Rheumatoid Arthritis Receiving Tofacitinib or Placebo With Background Methotrexate

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02147587
• Collaborator: (none)
• Enrollment: 112
• Locations: 36
• Arms: 2
• Actual Duration (Months): 13
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate immune response following administration of zoster vaccine in subjects with rheumatoid arthritis who are receiving background methotrexate and initiate 5 mg twice daily of tofacitinib or placebo for tofacitinib 2 to 3 weeks following vaccination.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Tofacitinib; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 2 Study To Assess The Immune Response Following Administration Of Zoster Vaccine To Subjects With Rheumatoid Arthritis Receiving Tofacitinib (Cp-690,550) Or Placebo With Background Methotrexate Treatment
• Actual Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tofacitinib 5 mg BID (oral) (70 subjects) Zoster vaccine will be administered to subjects on background methotrexate; treatment with 5 mg tofacitinib twice daily will begin 2 to 3 weeks following vaccination and continue for 12 weeks.	Drug: Tofacitinib; 5 mg twice daily of tofacitinib with background methotrexate for 12 weeks
Placebo Comparator: Placebo tofacitinib BID (oral) (70 subjects) Zoster vaccine will be administered to subjects on background methotrexate; treatment with placebo twice daily will begin 2 to 3 weeks following vaccination and continue for 12 weeks.	Drug: Placebo; Placebo tablets twice daily with background methotrexate for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Immunoglobulin G (IgG) Levels at Week 4 [Baseline (pre-vaccination; Day -14), Week 4 (6 weeks post-vaccination)]

   VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA).

Secondary Outcome Measures

1. Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12 [Baseline (pre-vaccination; Day -14), Day 1 (2 weeks post-vaccination), Week 12 (14 weeks post-vaccination)]

2. Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12 [Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)]

   The absolute geometric mean titer (GMT) of VZV-specific IgG levels was calculated from logarithmically transformed assay values.

3. Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12 [Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)]

   VZV-specific IgG levels as measured by ELISA. A ratio greater than or equal to (>=)1.5 was defined as a responder.

Other Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Baseline up to Week 16]

   An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 16 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.

2. Number of Participants With Zoster Vaccine-Related AEs by System Organ Class [Baseline up to Week 16]

   Zoster vaccine-related AEs included General Disorders and Administration Site Conditions (injection site erythema, pain, pruritis, rash, swelling; vaccination site erythema, pruritus, rash), Infections and Infestations (disseminated herpes zoster), and Musculoskeletal and Connective Tissue Disorders (myalgia). All zoster vaccine-related AEs were mild, except for the herpes zoster AE classified under Infections and Infestations, which was moderate in severity.

3. Number of Participants With Clinical Herpes Zoster Events by Severity [Baseline up to Week 16]

   Clinical herpes is manifested as mild, moderate, or severe disseminated herpes zoster.

4. Number of Participants With Clinically Significant Abnormal Laboratory Parameters [Baseline up to Week 16]

   Participants with the following abnormalities were discontinued from the study: 2 sequential absolute neutrophil counts (ANC) <1000/mm^3; 2 sequential hemoglobin values <8.0 g/dL or decreases of >30% from baseline value; 2 sequential absolute lymphocyte count <500/mm^3; 2 sequential platelet counts <75,000/mm^3; 2 sequential alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >=3 times the upper limit of normal (X ULN) with a total bilirubin value >=2X ULN, elevated international normalized ratio (INR), or accompanied by signs/symptoms consistent with hepatic injury; 2 sequential ALT or AST elevations >=5X ULN regardless of total bilirubin or accompanying symptoms; confirmed increases in serum creatinine (SCr) >50% over the average of screening and baseline values; a confirmed positive urine pregnancy test or refusal to use appropriate contraception in a woman of childbearing potential.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have moderate to severe rheumatoid arthritis inadequately controlled by methotrexate as defined by the American College of Rheumatology (ACR) classification criteria for Rheumatoid arthritis, painful and swollen joint counts and C-reactive protein (CRP).

• Screening CRP >3 mg/L or CDAI score > 10 at screening or at baseline before vaccination.

• Subjects must have active disease at screening and baseline.

• Must be at least 50 years of age or older.

Exclusion Criteria:

• History of receiving any varicella-zoster virus vaccine

• Receipt of any vaccines within 6 weeks of first dose of study treatment.

• Subjects with current infections or history of infections.

• History of recurrent (more than one episode) of herpes zoster or disseminated (a single episode) of herpes zoster or disseminated (a single episode) of herpes simplex.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NEA Baptist Clinic	Jonesboro	Arkansas	United States	72401
2	Drug Shipping Address (IRB# 14-000826) Ronald Regan	Los Angeles	California	United States	90095
3	UCLA David Geffen School of Medicine	Los Angeles	California	United States	90095
4	Pacific Arthritis Center Medical Group	Santa Maria	California	United States	93454
5	Inland Rheumatology Clinical Trials, Inc.	Upland	California	United States	91786
6	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
7	Center for Arthritis and Rheumatic Diseases	Miami	Florida	United States	33173
8	Suncoast Clinical Research, Inc.	New Port Richey	Florida	United States	34652
9	DMI Research, Inc.	Pinellas Park	Florida	United States	33782
10	Florida Arthritis and Osteoporosis Center	Port Richey	Florida	United States	34668
11	Gulf Coast Medical Center	Port Richey	Florida	United States	34668
12	Suncoast Medical Clinic	Saint Petersburg	Florida	United States	33705
13	Sun Coast Medical Clinic	Saint Petersburg	Florida	United States	33710
14	Sarasota Arthritis Research Center	Sarasota	Florida	United States	34239
15	Health Point Medical Group, Inc.	Tampa	Florida	United States	33614
16	Deerbrook Medical Associates	Vernon Hills	Illinois	United States	60061
17	Diagnostic Rheumatology And Research, PC	Indianapolis	Indiana	United States	46227
18	Arthritis Treatment Center	Frederick	Maryland	United States	21702
19	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	The Center for Rheumatology, LLP	Albany	New York	United States	12206
21	Buffalo Rheumatology and Medicine, PLLC	Orchard Park	New York	United States	14127
22	Piedmont Rheumatology, P.A	Hickory	North Carolina	United States	28602
23	PMG Research of Hickory, LLC	Hickory	North Carolina	United States	28602
24	PMG Research of Salisbury, LLC	Salisbury	North Carolina	United States	28144
25	Novant Health Imaging Julian Road	Salisbury	North Carolina	United States	28147
26	East Penn Rheumatology Associates, PC	Bethlehem	Pennsylvania	United States	18015
27	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
28	Clinical Research Center of Reading LLP	Wyomissing	Pennsylvania	United States	19610
29	Palmetto Clinical Trial Services, LLC	Greenville	South Carolina	United States	29601
30	Arthritis Clinic	Jackson	Tennessee	United States	38305
31	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
32	Rheumatology Consultants, PLLC	Knoxville	Tennessee	United States	37909-1907
33	Office of John P. Lavery, MD, PA	Allen	Texas	United States	75013
34	Baylor Research Institute Arthritis Care and Research Center	Dallas	Texas	United States	75231
35	The Vancouver Clinic (Drug Shipment Only)	Vancouver	Washington	United States	98664
36	The Vancouver Clinic, Inc, PS	Vancouver	Washington	United States	98664

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02147587
• Other Study ID Numbers: A3921237; 2014-000706-34
• First Posted: May 28, 2014
• Last Update Posted: Apr 11, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Tofacitinib

Study Results

Participant Flow

Pre-assignment Detail	The zoster vaccine was administered at least 2 weeks (14 to 21 days) prior to initiation of CP-690,550 (tofacitinib) or placebo in rheumatoid arthritis (RA) participants on background methotrexate therapy.

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Period Title: Overall Study
STARTED	57	55
COMPLETED	46	50
NOT COMPLETED	11	5

Baseline Characteristics

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day	Total
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.	Total of all reporting groups
Overall Participants	57	55	112
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.0 (8.7)	61.7 (6.2)	61.8 (7.6)
Sex: Female, Male (Count of Participants)
Female	38 66.7%	42 76.4%	80 71.4%
Male	19 33.3%	13 23.6%	32 28.6%

Outcome Measures

1. Primary Outcome

Title	Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Immunoglobulin G (IgG) Levels at Week 4
Description	VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA).
Time Frame	Baseline (pre-vaccination; Day -14), Week 4 (6 weeks post-vaccination)

Outcome Measure Data

Analysis Population Description

The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	53	54
Geometric Mean (80% Confidence Interval) [fold rise]	1.736	2.105

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	Geometric Mean Fold Rise (GMFR) for Tofacitinib versus Placebo (Week 4)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of GMFR
	Estimated Value	1.213
	Confidence Interval	(2-Sided) 80%; 1.033 to 1.424
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of GMFRs (Tofacitinib/Placebo) at Week 4

2. Secondary Outcome

Title	Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12
Time Frame	Baseline (pre-vaccination; Day -14), Day 1 (2 weeks post-vaccination), Week 12 (14 weeks post-vaccination)

Outcome Measure Data

Analysis Population Description

The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	53	54
Day 1	1.947	2.005
Week 12	1.496	1.636

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	GMFR for Tofacitinib versus Placebo (Day 1)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of GMFR
	Estimated Value	1.030
	Confidence Interval	(2-Sided) 80%; 0.877 to 1.209
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of GMFRs (Tofacitinib/Placebo) at Day 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	GMFR for Tofacitinib versus Placebo (Week 12)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of GMFR
	Estimated Value	1.093
	Confidence Interval	(2-Sided) 80%; 0.924 to 1.294
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of GMFRs (Tofacitinib/Placebo) at Week 12

3. Secondary Outcome

Title	Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12
Description	The absolute geometric mean titer (GMT) of VZV-specific IgG levels was calculated from logarithmically transformed assay values.
Time Frame	Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)

Outcome Measure Data

Analysis Population Description

The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	53	54
Day 1	361.603	384.219
Week 4	322.486	403.422
Week 12	278.599	312.328

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	Geometric Mean Titer (GMT) for Tofacitinib versus Placebo (Day 1)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of GMT
	Estimated Value	1.063
	Confidence Interval	(2-Sided) 80%; 0.821 to 1.375
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of GMTs (Tofacitinib/Placebo) at Day 1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	GMT for Tofacitinib versus Placebo (Week 4)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of GMT
	Estimated Value	1.251
	Confidence Interval	(2-Sided) 80%; 0.967 to 1.618
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of GMTs (Tofacitinib/Placebo) at Week 4

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	GMT for Tofacitinib versus Placebo (Week 12)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of GMT
	Estimated Value	1.121
	Confidence Interval	(2-Sided) 80%; 0.862 to 1.459
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of GMTs (Tofacitinib/Placebo) at Week 12

4. Secondary Outcome

Title	Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12
Description	VZV-specific IgG levels as measured by ELISA. A ratio greater than or equal to (>=)1.5 was defined as a responder.
Time Frame	Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)

Outcome Measure Data

Analysis Population Description

The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	53	54
Day 1	47.17 82.8%	55.56 101%
Week 4	43.40 76.1%	57.41 104.4%
Week 12	43.18 75.8%	45.83 83.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	Tofacitinib versus Placebo (Day 1)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	8.39
	Confidence Interval	(2-Sided) 80%; -4.05 to 20.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	Tofacitinib versus Placebo (Week 4)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	14.01
	Confidence Interval	(2-Sided) 80%; 1.57 to 26.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo Twice a Day, Tofacitinib 5 mg Twice a Day
	Comments	Tofacitinib versus Placebo (Week 12)
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	2.65
	Confidence Interval	(2-Sided) 80%; -10.66 to 15.83
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 16 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	57	55
AEs	21 36.8%	16 29.1%
SAEs	0 0%	3 5.5%

6. Other Pre-specified Outcome

Title	Number of Participants With Zoster Vaccine-Related AEs by System Organ Class
Description	Zoster vaccine-related AEs included General Disorders and Administration Site Conditions (injection site erythema, pain, pruritis, rash, swelling; vaccination site erythema, pruritus, rash), Infections and Infestations (disseminated herpes zoster), and Musculoskeletal and Connective Tissue Disorders (myalgia). All zoster vaccine-related AEs were mild, except for the herpes zoster AE classified under Infections and Infestations, which was moderate in severity.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	57	55
General and Administration Site Conditions	2 3.5%	4 7.3%
Infections and Infestations	0 0%	1 1.8%
Musculoskeletal and Connective Tissue Disorders	0 0%	1 1.8%

7. Other Pre-specified Outcome

Title	Number of Participants With Clinical Herpes Zoster Events by Severity
Description	Clinical herpes is manifested as mild, moderate, or severe disseminated herpes zoster.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	57	55
Mild Herpes Zoster	0 0%	0 0%
Moderate Herpes Zoster	0 0%	1 1.8%
Severe Herpes Zoster	0 0%	0 0%

8. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Abnormal Laboratory Parameters
Description	Participants with the following abnormalities were discontinued from the study: 2 sequential absolute neutrophil counts (ANC) <1000/mm^3; 2 sequential hemoglobin values <8.0 g/dL or decreases of >30% from baseline value; 2 sequential absolute lymphocyte count <500/mm^3; 2 sequential platelet counts <75,000/mm^3; 2 sequential alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations >=3 times the upper limit of normal (X ULN) with a total bilirubin value >=2X ULN, elevated international normalized ratio (INR), or accompanied by signs/symptoms consistent with hepatic injury; 2 sequential ALT or AST elevations >=5X ULN regardless of total bilirubin or accompanying symptoms; confirmed increases in serum creatinine (SCr) >50% over the average of screening and baseline values; a confirmed positive urine pregnancy test or refusal to use appropriate contraception in a woman of childbearing potential.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).

Arm/Group Title	Placebo Twice a Day	Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.	Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
Measure Participants	57	55
Number [participants]	1 1.8%	0 0%

Adverse Events

Time Frame	Baseline up to Week 16
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
Arm/Group Title	Placebo Twice a Day		Tofacitinib 5 mg Twice a Day
Arm/Group Description	Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.		Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
All Cause Mortality
	Placebo Twice a Day		Tofacitinib 5 mg Twice a Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo Twice a Day		Tofacitinib 5 mg Twice a Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		3/55 (5.5%)
Hepatobiliary disorders
Bile duct stone	0/57 (0%)	0	1/55 (1.8%)	1
Cholangitis	0/57 (0%)	0	1/55 (1.8%)	1
Infections and infestations
Bronchitis	0/57 (0%)	0	1/55 (1.8%)	1
Herpes zoster disseminated	0/57 (0%)	0	1/55 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Placebo Twice a Day		Tofacitinib 5 mg Twice a Day
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/57 (15.8%)		6/55 (10.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/57 (0%)	0	3/55 (5.5%)	3
Rheumatoid arthritis	9/57 (15.8%)	9	3/55 (5.5%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.