Oral Treatment Option for RA Includes Tofacitinib (XELJANZ®) Plus Methotrexate

MedicalResearch.com Interview with:

Roy Fleischmann, MD MACR Medical Director Metroplex Clinical Research Center Clinical Professor of Medicine University of Texas Southwestern Medical Center Dallas, TX 75231

Dr. Fleischmann

Roy Fleischmann, MD MACR
Medical Director
Metroplex Clinical Research Center
Clinical Professor of Medicine
University of Texas Southwestern Medical Center
Dallas, TX 75231

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In the phase 3 studies of tofacitinib, it was noted that the clinical responses to tofacitinib monotherapy were higher than the responses to tofaciotinib plus MTX and that tofacitinib plus methotrexate had numerically higher clinical responses compared to adalimumab plus methotrexate. This study was a non-inferiority design which compared tofacitinib monotherapy to tofacitinib + MTX and to adalimumab +MTX and tofacitinib monotherapy to tofacitinib +MTX in MTX incomplete responders. It was found that tofacitinib + MTX is non-inferior to adalimumab + MTX (and vice versa) and neither was superior to the other. The results of tofacitinib to either combination was non-conclusive showing neither non-inferiority or inferiority, but suggesting that either combination will be effective in more patients in a group of patients.

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Gum Disease Linked to Autoimmunity in Rheumatoid Arthritis

MedicalResearch.com Interview with:

Maximilian F. Konig, MD Department of Medicine Massachusetts General Hospital Harvard Medical School

Dr. Maximilian F. Konig

Maximilian F. Konig, MD
Division of Rheumatology,
Johns Hopkins University School of Medicine
Current affiliation:
Department of Medicine
Massachusetts General Hospital
Harvard Medical School

MedicalResearch.com: What is the background for this study?

Response:The idea that rheumatoid arthritis (RA), an autoimmune disease that leads to chronic joint inflammation and destruction, may be initiated by a bacterial infection is not novel, but has been posited for more than a century. Based on the clinical observation that patients with RA frequently have severe periodontal disease (gum disease), gum inflammation has long been thought to contribute to disease development in RA. However, limited understanding of the mechanisms that fuel and sustain the autoimmune attack in RA made it difficult to pinpoint a specific bacterial trigger.

In recent years, our understanding of the abnormal immune response that attacks the joints in patients with RA has grown exponentially, and we now know that disease-specific autoantibodies (ACPAs) target modified self-proteins (this modification is known as citrullination). It is this abnormal immune response against citrullinated proteins that appears to drive the joint (and sometimes lung) inflammation seen in rheumatoid arthritis. Recent studies from our laboratory at The Johns Hopkins University (led by principle investigator Felipe Andrade, MD, PhD) suggested that an immune cell called the neutrophil, which normally protects us from infection at sites like the oral cavity or anywhere else in the body, also appears to be the source of the proteins attacked in RA. We were therefore interested to understand what drives the association of gum disease, an inflammation commonly triggered by bacteria, with RA.

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Non–TNF-Targeted Biologic Found Superior to Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug

MedicalResearch.com Interview with:
Jacques-Eric Gottenberg, MD, PhD Department of Rheumatology National Reference Center for Systemic Autoimmune Diseases Strasbourg University Hospital, Université de Strasbourg Strasbourg, FranceJacques-Eric Gottenberg, MD, PhD
Department of Rheumatology
National Reference Center for Systemic Autoimmune Diseases
Strasbourg University Hospital, Université de Strasbourg
Strasbourg, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is no recommendation for the choice of the second biologic in patients with rheumatoid arthritis and insufficient response to a first anti-TNF, which is a common situation in our daily practice (approximately one third of patients treated with anti-TNF). We therefore conducted the first randomized trial to date to investigate the best strategy in such a setting.

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Rheumatoid Arthritis: Oral JAK Inhibitor Tofacitinib May Be Superior to Methotrexate

Bethanie Wilkinson, Ph.D. Pfizer  445 Eastern Point Rd. Groton, CT 06340MedicalResearch.com Interview with
Bethanie Wilkinson, Ph.D.
Pfizer
445 Eastern Point Rd.
Groton, CT 06340

 

MedicalResearch: What are the main findings of the study?

Dr. Wilkinson: ORAL Start showed that XELJANZ (tofacitinib citrate) 5 and 10 mg twice daily (BID), taken by itself without methotrexate (MX), inhibited the progression of structural damage and reduced the signs and symptoms of rheumatoid arthritis (RA), and was statistically significantly superior to methotrexate on these measures at Month 6 (primary endpoint) and at all measured time points up to 24 months in patients with rheumatoid arthritis who had not previously received methotrexate or therapeutic doses of methotrexate.  XELJANZ is not indicated in patients who had not previously received methotrexate.

  •  Both doses of XELJANZ met the study’s co-primary efficacy endpoints of mean change from baseline in van der Heijde modified Total Sharp Score (mtss) [0.18 and 0.04 (both P<0.001) for tofacitinib 5 and 10 mg BID, respectively, versus 0.84 for MTX], and ACR70 response rates [25.5% and 37.7% for tofacitinib 5 and 10 mg BID (both P<0.001) versus 12.0% for MTX], at Month 6.
  • These results were sustained at all measured time points up to 24 months.

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Rheumatoid Arthritis: Personalized Treatment Approach Guided By MBDA Score

MedicalResearch.com Interview with:
Karen Hambardzumyan
Research Assistant
Karolinska Institute
Department of Medicine, (ClinTRID)
D1:00, Karolinska University Hospital
Solna Stockholm

MedicalResearch: What are the main findings of the study?

Answer: One of the difficulties with rheumatoid arthritis (RA) treatment is unpredictable treatment outcome at the individual patient level. The course might be mild or severe independently of the therapy. To identify subgroups of patients who will benefit from specific therapy strategies is one of the goals for today’s rheumatologists. We have investigated a Multi-Biomarker Disease Activity (MBDA) score in patients from the Swedish Farmacotherapy (SWEFOT) clinical trial, where early rheumatoid arthritis patients were included/studied. The main finding was the usefulness of the MBDA score for prediction of those patients who will not get joint damage detected by X-rays (radiographic progression) during one year follow-up. This MBDA score, developed by Crescendo Bioscience (South San-Francisco, CA, USA) is based on serum levels of 12 different protein biomarkers and can categorize patients into 3 groups: patients with low, moderate and high disease activity. Ninety-seven percent of patients who had low or moderate MBDA score before treatment onset, did not experience radiographic progression during one year follow-up. This finding could contribute to a personalised approach to the RA patients for the optimal therapy choice.
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