A Study Of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to or Are Unable to Tolerate Biologic and Non-Biologic Disease-modifying Antirheumatic Drugs (DMARDs)

Browse trials for

• Arthritis 3,554
• Arthritis, Rheumatoid 2,888

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 886 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Tocilizumab 8 mg/kg Monotherapy

  Participants received Tocilizumab 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.

  Drug: tocilizumab [RoActemra/Actemra]

• Experimental
  Tocilizumab 4 mg/kg + DMARD

  Participants received Tocilizumab (TCZ) 4 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants not achieving a 20% improvement from baseline in tender and swollen joint counts at Week 8 were to have their dosage increased to 8 mg/kg, per protocol. Beginning at Week 12 dosage increase to 8 mg/kg was at the discretion of the investigator. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.

  Drug: tocilizumab [RoActemra/Actemra] · Drug: Nonbiologic DMARDs of investigator's choice

• Experimental
  Tocilizumab 8 mg/kg + DMARD

  Participants received Tocilizumab (TCZ) 8 mg/kg as a 60 minute intravenous infusion every 4 weeks for a total of 6 infusions plus non-biologic disease-modifying antirheumatic drug (DMARD) of the investigator's choice for 24 weeks. Participants who completed the 24 week treatment period were offered the option of entering a long-term extension phase at the investigator's discretion.

  Drug: tocilizumab [RoActemra/Actemra] · Drug: Nonbiologic DMARDs of investigator's choice

Interventions

• Drugtocilizumab [RoActemra/Actemra]

  8 mg/kg intravenous every 4 weeks for 24 weeks

• Drugtocilizumab [RoActemra/Actemra]

  4 mg/kg every 4 weeks for 24 weeks

• DrugNonbiologic DMARDs of investigator's choice

  Nonbiologic disease-modifying antirheumatic drugs (DMARDs) As prescribed

Primary outcomes

1. Percentage of Participants Experiencing at Least One Serious Adverse Event (SAE) During the 24 Week Treatment Period

   An SAE was any adverse event that at any dose fulfilled at least one of the following criteria: * Was fatal (results in death) * Was life-threatening * Required in-patient hospitalization or prolongation of existing hospitalization * Resulted in persistent or significant disability/incapacity * Was a congenital anomaly/birth defect * Was medically significant or required intervention to prevent one or other of the outcomes listed above.

   Time frame: 24 Weeks

Secondary outcomes

1. Percentage of Participants Experiencing Serious Adverse Events of Special Interest

   Serious Adverse Events of Special interest include: * Serious infections including opportunistic infections * Complications of diverticulitis (including lower gastrointestinal \[GI\] perforations) * Myocardial infarction/acute coronary syndrome * Stroke * Spontaneous or serious bleeding * Malignant neoplasms

   Time frame: 24 Weeks

2. Percentage of Participants Experiencing Non-serious Adverse Events of Special Interest

   Non-serious adverse Events of Special interest include: * Serious/Medically Significant Hepatic Events * Spontaneous /Serious Bleeding * Malignant Neoplasms

   Time frame: 24 Weeks

3. Percentage of Participants Achieving Clinical Remission at Weeks 8, 16, and 24

   Clinical Remission is defined as a Disease Activity Score 28 \[DAS28\] \< 2.6. The DAS28 is a combined index for measuring disease activity in RA. The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

   Time frame: Weeks 8,16,24

4. Change From Baseline in DAS28 Score at Weeks 8, 16 and 24

   The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes tender joint count (TJC) -28 joints and swollen joint count (SJC)-28 joints, acute phase response C-reactive protein (CRP) and general health status. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A score of \< 2.6 represents clinical remission, a score of ≤ 3.2 represents low disease activity, and a score of \> 5.1 represents high disease activity. The Change from Baseline to Weeks 8, 16 and 24 is reported.

   Time frame: Baseline, Weeks 8,16,24

5. Percentage of Participants Achieving American College of Rheumatology (ACR) (ACR20/50/70) Responses at Weeks 8, 16, and 24

   The ACR response rates ACR20, ACR50, and ACR70 are defined as ≥20%, ≥50%, and ≥70% improvement from baseline, respectively, in: 1. Swollen Joint Count (66 joints) and Tender Joint Count (68 joints) and 2. At least 3 of the following 5 assessments: * Patient's global assessment of pain-Visual Analog Scale (VAS) * Patient global assessment of disease activity-(VAS) * Physician global assessment of disease activity-(VAS) * Patient assessment of disability (physical function scale of the Multidimensional Health Assessment Questionnaire) * Acute phase response C-Reactive Protein (CRP)

   Time frame: Baseline, Weeks 8,16,24

6. Percentage of Participants With Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Week 8

   Dosage could be increased from 4 mg/kg Tocilizumab to 8 mg/kg due to failure to achieve 20% improvement from baseline in swollen and tender joint counts.

   Time frame: Baseline, Week 8

7. Number of Participants Having Their Tocilizumab Dose Increased From 4 mg/kg to 8 mg/kg at Weeks 12, 16, and 20

   Dosage of Tocilizumab 4 mg/kg could be increased to 8 mg/kg at the discretion of the investigator based on assessment of the patient's benefit-risk after Week 12.

   Time frame: Weeks 12,16, 20

8. Change From Baseline in Routine Assessment Patient Index Data (RAPID3) Score at Weeks 8, 16, and 24

   The RAPID3 is a combined index derived from the Multidimensional Health Assessment Questionnaire that includes physical function score, pain Visual Analog Scale (VAS), and global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 10 where higher scores represent worse outcomes. A negative change from baseline indicates improvement.

   Time frame: Baseline, Weeks 8,16,24

9. Change From Baseline in Fatigue Visual Analogue Scale (VAS) at Weeks 8, 16, and 24

   The fatigue VAS is a single-item, patient-reported outcome that measures the severity of the fatigue over the past week. Patients rate their fatigue on a scale of 0 (fatigue is no problem) to 100 (fatigue is a major problem). Higher scores represent higher disease activity and a negative change from baseline indicates improvement.

   Time frame: Baseline, Weeks 8,16,24

Baseline characteristics

Publications

• Weinblatt ME, Kremer J, Cush J, Rigby W, Teng LL, Devenport J, Singh N, Lepley D, Genovese MC. Tocilizumab as monotherapy or in combination with nonbiologic disease-modifying antirheumatic drugs: twenty-four-week results of an open-label, clinical practice study. Arthritis Care Res (Hoboken). 2013 Mar;65(3):362-71. doi: 10.1002/acr.21847. PubMed 22972745 ↗