Trial Outcomes & Findings for Methotrexate (Rheumatrex) High Dose Special Investigation (Regulatory Post Marketing Commitment Plan) (NCT NCT01414257)

Last Updated: 2018-08-06

Results Overview

A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate.

Recruitment status

COMPLETED

Target enrollment

2860 participants

Primary outcome timeframe

24 Weeks

Results posted on

2018-08-06

Participant Flow

Participant milestones

Participant milestones
Measure	Methotrexate
Overall Study STARTED	2860
Overall Study COMPLETED	2838
Overall Study NOT COMPLETED	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Methotrexate
Overall Study No Visit After First Day of Treatment	12
Overall Study Protocol Violation	10

Baseline Characteristics

Methotrexate (Rheumatrex) High Dose Special Investigation (Regulatory Post Marketing Commitment Plan)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methotrexate n=2838 Participants
Age, Customized ≥15 to <65 years	2014 Participants n=99 Participants
Age, Customized ≥65 years	804 Participants n=99 Participants
Age, Customized Unknown	20 Participants n=99 Participants
Sex/Gender, Customized Female	2176 Participants n=99 Participants
Sex/Gender, Customized Male	659 Participants n=99 Participants
Sex/Gender, Customized Unknown	3 Participants n=99 Participants
Steinbrocker Stage Stage I (Initial)	695 Participants n=99 Participants
Steinbrocker Stage Stage II (Medium)	948 Participants n=99 Participants
Steinbrocker Stage Stage III (Progressive)	613 Participants n=99 Participants
Steinbrocker Stage Stage IV (Terminal)	524 Participants n=99 Participants
Steinbrocker Stage Unknown	58 Participants n=99 Participants
Steinbrocker Class Class 1	794 Participants n=99 Participants
Steinbrocker Class Class 2	1641 Participants n=99 Participants
Steinbrocker Class Class 3	301 Participants n=99 Participants
Steinbrocker Class Class 4	16 Participants n=99 Participants
Steinbrocker Class Unknown	86 Participants n=99 Participants
Morbidity Period <1 year	443 Participants n=99 Participants
Morbidity Period 1 to ˂3 years	512 Participants n=99 Participants
Morbidity Period 3 to ˂5 years	313 Participants n=99 Participants
Morbidity Period ≥5 years	1148 Participants n=99 Participants
Morbidity Period Unknown	422 Participants n=99 Participants
History of Methotrexate Therapy ˂0.5 year	737 Participants n=99 Participants
History of Methotrexate Therapy 0.5 to ˂1 year	254 Participants n=99 Participants
History of Methotrexate Therapy 1 to ˂3 years	547 Participants n=99 Participants
History of Methotrexate Therapy 3 to ˂5 years	300 Participants n=99 Participants
History of Methotrexate Therapy ≥5 years	436 Participants n=99 Participants
History of Methotrexate Therapy Unknown	554 Participants n=99 Participants
History of Methotrexate Therapy Not used Methotrexate Previously	10 Participants n=99 Participants

PRIMARY outcome

Timeframe: 24 Weeks

Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received methotrexate at least once.

A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate.

Outcome measures

Outcome measures
Measure	Methotrexate n=2838 Participants
Number of Participants With Treatment-Related Adverse Events	608 Participants

PRIMARY outcome

Timeframe: Baseline and 24 Weeks

Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (ESR) at least once. Participants with observed DAS28-4(ESR) were included in table.

Disease activity score based on 28-joint count and erythrocyte sedimentation rate (4 variables) (DAS28-4 \[ESR\]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, ESR (mm/hour) and visual analogue scale (VAS) of general health assessed by participant or investigator. Higher score indicated more disease activity. The total scale range of DAS28-4 (ESR) , minimum is 0.0 and maximum can not be specified. DAS28-4 (ESR) \>5.1 indicated high disease activity, ?3.2 to ?5.1 indicated moderate disease activity, \<3.2 indicated low disease activity, and \<2.6 indicated remission.

Outcome measures

Outcome measures
Measure	Methotrexate n=1526 Participants
Disease Activity Score (DAS28)-4ESR At Baseline	4.09 Score Standard Deviation 1.235
Disease Activity Score (DAS28)-4ESR At 24 Weeks	3.21 Score Standard Deviation 1.235

PRIMARY outcome

Timeframe: Baseline and 24 Weeks

Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (CRP) at least once. Participants with observed DAS28-4(CRP) were included in table.

Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 \[CRP\]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. The total scale range of DAS28-4 (ESR) , minimum is 0.0 and maximum can not be specified. DAS28-4 (CRP) \>4.1 indicated high disease activity, ≥2.7 to 4.1 indicated moderate disease activity, \<2.7 indicated low disease activity, and \<2.3 indicated remission.

Outcome measures

Outcome measures
Measure	Methotrexate n=1818 Participants
Disease Activity Score (DAS28)-4CRP At Baseline	3.55 Score Standard Deviation 1.148
Disease Activity Score (DAS28)-4CRP At 24 Weeks	2.66 Score Standard Deviation 1.076

PRIMARY outcome

Timeframe: Baseline and 24 Weeks

Outcome measures

Outcome measures
Measure	Methotrexate n=1526 Participants
Change From Baseline in Disease Activity Score (DAS28)-4ESR	-0.88 Score Standard Deviation 1.156

PRIMARY outcome

Timeframe: Baseline and 24 Weeks

Disease activity score based on 28-joint count and C-reactive protein (4 variables) (DAS28-4 \[CRP\]) was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, C-reactive protein (CRP, mg/dL) and VAS of general health. Mean change from baseline in the DAS28-4 (CRP) at Week 24 is calculated. The total scale range can not be specified.

Outcome measures

Outcome measures
Measure	Methotrexate n=1818 Participants
Change From Baseline in Disease Activity Score (DAS28)-4CRP	-0.89 Score Standard Deviation 1.117

SECONDARY outcome

Timeframe: 24 Weeks

Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received methotrexate at least once.

A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Methotrexate n=2838 Participants
Number of Participants With Treatment-Related Serious Adverse Events	47 Participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: The safety analysis set comprised of participants who satisfied the inclusion criteria and had received methotrexate at least once.

Pre-specified important adverse events were 1) Interstitial pneumonia, 2) Pulmonary fibrosis, 3) Hepatic impairment, 4) Renal impairment, 5) Hematopoietic disorder, 6) Infection, and 7) Lymphoma. A treatment-related adverse event was any untoward medical occurrence attributed to methotrexate in a participant who received methotrexate. A treatment-related serious adverse event was a treatment-related adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness to methotrexate was assessed by the investigator.

Outcome measures

Outcome measures
Measure	Methotrexate n=2838 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Lymphoma	4 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Interstitial Pneumonia	7 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Pulmonary Fibrosis	0 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Hepatic Impairment	1 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Renal Impairment	1 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Hematopoietic Disorder	3 Participants
Number of Participants With Treatment Related Pre-specified Important Serious Adverse Events Infection	28 Participants

SECONDARY outcome

Timeframe: 24 Weeks

Population: The effectiveness analysis set comprised of participants in the safety analysis set who had effectiveness evaluation (clinical efficacy rate) at least once. Participants with observed effectiveness data were included in table.

Clinical efficacy rate, which was defined as the percentage of participants who achieved clinical effectiveness over the total number of assesable effectiveness analysis population, was presented along with the corresponding 2-sided 95% CI. Clinical effectiveness of methotrexate was assessed as "effective" or "ineffective" by the investigator. The assessment was based on the baseline condition of disease control and degree of alleviation from baseline in clinical symptoms and laboratory data.

Outcome measures

Outcome measures
Measure	Methotrexate n=2190 Participants
Clinical Efficacy Rate	80.2 Percentage of Participants Interval 78.5 to 81.9

Adverse Events

Methotrexate

Serious events: 69 serious events

Other events: 340 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Methotrexate n=2838 participants at risk
Infections and infestations Pneumonia	0.35% 10/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumocystis jirovecii pneumonia	0.18% 5/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.07% 2/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia mycoplasmal	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Liver abscess	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchopneumonia	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Acute tonsillitis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Tuberculous pleurisy	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Ear infection	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia pneumococcal	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lung infection	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.14% 4/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.07% 2/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.07% 2/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma recurrent	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Lymphadenopathy	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Pancytopenia	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Subarachnoid haemorrhage	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haemorrhage	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Ear and labyrinth disorders Vertigo	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Aortic valve incompetence	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Deep vein thrombosis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric polyps	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Duodenal ulcer	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Large intestine polyp	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Enterocolitis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obstruction	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Liver disorder	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Skin ulcer	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure acute	0.07% 2/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Congenital, familial and genetic disorders Cerebrovascular arteriovenous malformation	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.07% 2/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Administration site reaction	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Platelet count decreased	0.07% 2/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Helicobacter test positive	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count decreased	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Airway burns	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fracture	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Heat illness	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Tendon rupture	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Hip arthroplasty	0.04% 1/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.25% 7/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Other adverse events
Measure	Methotrexate n=2838 participants at risk
Gastrointestinal disorders Stomatitis	1.3% 37/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	7.6% 217/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Liver disorder	2.0% 57/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations White blood cell count decreased	1.0% 29/2838 The frequency of adverse events. The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER