Anti-TNF Agents In Inflammatory Bowel Disease Linked to Small Increased Risk of Lymphoma

MedicalResearch.com Interview with:
ANSM
Rosemary Dray-Spira, MD, PhD
Department of Epidemiology
French National Agency for Medicines and Health Products Safety (ANSM)
Saint-Denis, France

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

Response: Anti-tumor necrosis factor (anti-TNF) agents are increasingly used for the management of inflammatory bowel diseases (IBD), either alone or in combination with thiopurines. Their clinical benefits have been largely assessed, however they may expose to potentially serious adverse effects. While an increased risk of lymphoma has been established with thiopurines, up to now such a risk of lymphoma remained uncertain with anti-TNF agents.

In this study based upon a large, nationwide cohort of 189,289 patients with IBD, the use of anti-TNF agents alone was found associated with a 2 to 3 fold increase in the risk of lymphoma, similarly to thiopurines alone. In addition, the combination of these two treatments was associated with a 6 fold increase in the risk of lymphoma, ie a higher risk than with each treatment used alone. Although these differences are statistically significant, the risk of lymphoma among patients exposed to anti-TNF agents is less than 1 case per 1000 person-years.

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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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Effect of Adalimumab on Visual Functioning in Patients With Noninfectious Uveitis

MedicalResearch.com Interview with:
Andrew Dick FRSB FMedSci

Professor of Ophthalmology
Bristol Eye Hospital, University of Bristol, Bristol, England
National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, Institute of Ophthalmology, University College London, London, England and
John Sheppard, MD
President, Virginia Eye Consultants
Professor of Ophthalmology, Eastern Virginia Medical School

MedicalResearch.com: What should readers take away from your report?

Dr. Andrew Dick: These findings demonstrate that adalimumab is associated with clinically meaningful improvements in visual functioning for patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. The emphasis of this work is that for the first time in uveitis we have seen patient reported outcome benefit of a biologic treatment. This analysis supports the use of adalimumab as a promising new treatment option, having demonstrated improvements in both clinical and visual functioning outcomes in patients with active and inactive uveitis.

Dr. John SheppardUveitis has a substantial effect on individuals’ physical, professional, psychological, avocational and social functioning in day-to-day life. Adalimumab, an anti-inflammatory drug that binds to tumor necrosis factor, was recently approved for the treatment of non-infectious intermediate uveitis, posterior uveitis, and panuveitis. It is the first systemic therapy specifically approved for uveitis.  The analyses in this study provide evidence that patients with noninfectious uveitis treated with adalimumab experience significant and clinically meaningful improvements in vision-related quality of life, compared with those who received placebo.

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Taltz Demonstrates Improved Clearing of Psoriasis Compared to Stelara

MedicalResearch.com Interview with:

Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg 07.04.2009 | Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg, Germany, 07.04.2009 | [© (c) Martin Zitzlaff, Emilienstr.78, 20259 Hamburg, Germany, Tel. +491711940261, http://www.zitzlaff.com, martin@zitzlaff.com, Postbank Hamburg BLZ 20010020 Kto.-Nr. 10204204, MwSt. 7%, Veroeffentlichung nur gegen Honorar (MFM) und Belegexemplar, mit Namensnennung]

Prof. Reich

Prof. Dr. med. Kristian Reich
Dermatologie, Allergologie
Psoriasis- und Neurodermitis-Trainer
Hamburg

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

Response: The IXORA-S study compared the efficacy and safety of Taltz® (ixekizumab) and Stelara®* (ustekinumab) for the treatment of moderate-to-severe plaque psoriasis at 24 weeks.

In this study, patients were randomized to receive either Stelara (45 mg or 90 mg weight-based dosing per label) or Taltz (80 mg every two weeks followed by 80 mg every four weeks), following an initial starting dose of 160 mg. At 24 weeks, patients treated with Taltz achieved significantly higher response rates compared to patients treated with Stelara, including 83 percent of patients who achieved Psoriasis Area Severity Index (PASI) 90—the study’s primary endpoint—compared to 59 percent of patients who achieved PASI 90 after treatment with Stelara.

Results at 24 weeks also found:
• 91.2 percent of patients treated with Taltz achieved PASI 75 compared to 81.9 percent of patients treated with Stelara (p=0.015)
• 49.3 percent of patients treated with Taltz achieved PASI 100 compared to 23.5 percent of patients treated with Stelara (p=0.001)
• 86.6 percent of patients treated with Taltz achieve static Physician’s Global Assessment score (sPGA) 0 or 1 compared to 69.3 percent of patients treated with Stelara (p<0.001)

The majority of treatment-emergent adverse events were mild or moderate. There were no statistically significant differences between treatment groups in overall treatment-emergent adverse events. The safety profile for Taltz was consistent with previous clinical trials.

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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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Skin Problems Common With anti-TNF therapy For IBD

Isabelle Cleynen PhD University of Leuven

Dr. Cleynen

MedicalResearch.com Interview with:
Isabelle Cleynen  PhD

University of Leuven 

Medical Research: What is the background for this study? What are the main findings?

Dr. Cleynen : Ulcerative colitis and Crohn’s disease, together inflammatory bowel disease (IBD), are characterized by chronic inflammation of the gastrointestinal tract. Treatment for IBD usually involves drug therapy including anti-inflammatory drugs and immune system repressors, amongst which biologics as the anti-TNF antibodies used for patients with moderate to severe IBD. Although these TNF-blocking drugs are effective in many patients with immune-mediated disorders like psoriasis, rheumatoid arthritis and spondylarthropathies, and IBD, several case reports and series showed that some patients developed troubling skin problems (including psoriasis and eczema), causing them to stop the anti-TNF treatment. It is however not clear how often these skin problems develop in IBD patients treated with anti-TNF, and what could be the predisposing factors.

In a retrospective cohort of 917 IBD patients initiated on anti-TNF therapy in a single center, we have studied which patients did and did not develop skin problems, what type of skin problems, how they were treated, and whether the lesions resolved upon treatment.

We found that about one third of the patients developed skin problems while being treated with anti-TNF drugs. The most common type was psoriasiform eczema, often occurring in flexural regions, the scalp, and genitalia. The time between starting the TNF-blocking drug and the appearance of the skin problem varied from less than half a year to more than 4 years. Quite surprisingly, we found that the cumulative dose of the treatment, or drug serum levels were not different in skin and non-skin lesion patients. Skin lesion patients however seemed to be younger when diagnosed with IBD and when started on anti-TNF agents, more often had anti-nuclear and dsDNA antibodies (both auto-immune factors), and a higher number of skin-disease related genetic risk variants. Most patients had a good response to treatment of their skin problem. About 10% of the patients who developed skin problems, however, stopped the TNF-blocking treatment because of this issue.

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How Many Screening Tests Are Needed For Psoriasis Patients on Biologics?

William W. Huang, MD, MPH Assistant Professor and Program Director Wake Forest School of Medicine Department of Dermatology Winston-Salem, NC 27104MedicalResearch.com Interview with:
William W. Huang, MD, MPH
Assistant Professor and Program Director
Wake Forest School of Medicine
Department of Dermatology
Winston-Salem, NC 27104

Medical Research: What is the background for this study? What are the main findings?
Dr. Huang: This particular study was an update of a previous study our group had published in 2008 (JAAD, 6/08). As the use of biologics in dermatology has increased dramatically in recent years, we wanted to evaluate the evidence for the screening and monitoring tests that are routinely performed for patients with psoriasis and psoriatic arthritis on biologic agents.

We found that current guidelines for screening and monitoring tests varied among various national organizations (Table 1) including the American Academy of Dermatology, Japanese Dermatology Association, European Academy of Dermatology and Venerology, and the British Association of Dermatologists. Using evidence grading based on methods developed by the US Preventative Services Task Force (USPSTF), we found that the evidence was strongest (Grade B) for tuberculosis screening. High level evidence was in general lacking for other routine screening and monitoring tests except in select populations (Table 2, Table 3).

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New Generation Biologic Markedly Improved Psoriasis

Prof. Dr. Kristian Reich, Dermatologikum Hamburg, Hamburg 07.04.2009 | Prof. Dr. Kristian Reich,  Dermatologikum Hamburg, Hamburg, Germany, 07.04.2009 | [© (c) Martin Zitzlaff, Emilienstr.78, 20259 Hamburg, Germany, Tel. +491711940261, http://www.zitzlaff.com, martin@zitzlaff.com, Postbank Hamburg BLZ 20010020 Kto.-Nr. 10204204, MwSt. 7%, Veroeffentlichung nur gegen Honorar (MFM) und Belegexemplar, mit Namensnennung] MedicalResearch.com Interview with:
Prof. Dr. med. Kristian Reich
DERMATOLOGIKUM HAMBURG
Hamburg

Medical Research: What is the background for this study? What are the main findings?

Prof. Reich: The Phase 2b X-PLORE study compared a new generation biologic therapy, guselkumab – an inhibitor of IL–23, with the anti–tumor necrosis factor (TNF)–alpha agent adalimumab (Humira®) and placebo in the treatment of moderate-to-severe plaque-type psoriasis. It showed that up to 86 percent of patients treated with guselkumab achieved a Physician’s Global Assessment (PGA) score of cleared psoriasis or minimal psoriasis at week 16, the study’s primary endpoint.  Interestingly, levels of efficacy were higher for several guselkumab doses through week 16 when compared to adalimumab. Improvements with guselkumab continued through week 40 with every eight- or twelve-week maintenance treatment.   Continue reading

Biologics in Rheumatic Disease Reduce Missed Workdays

MedicalResearch.com Interview with:
Cécile Gaujoux-Viala, MD, PhD
Université Montpellier I
Chef de Service de Rhumatologie
CHU de Nîmes Carémeau
France

Medical Research: What is the background for this study?

Response: Chronic inflammatory rheumatic diseases – such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)  – confer significant patient and economic burdens : 1/5 of people with rheumatic conditions has been forced to change career, 1/3 will have stopped working within two years of onset and 1/2 will be unable to work within ten years.

The addition of biological agents in treatment strategies for rheumatic diseases have improved the possibility of controlling disease activity and slowing the progression of joint damage. But these treatments are very expensive and their effect on work participation remains unclear.

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Not All Biologics For Psoriasis Carry Same Risk Of Serious Infections

MedicalResearch.com Interview with: Robert E Kalb, M.D. Clinical Professor of Dermatology State University of New York at Buffalo School of Medicine and Biomedical Sciences Buffalo Medical Group, P.C. Buffalo, NY 14221MedicalResearch.com Interview with:
Robert E Kalb, M.D.

Clinical Professor of Dermatology
State University of New York at Buffalo School of Medicine and Biomedical Sciences
Buffalo Medical Group, P.C.
Buffalo, NY 14221

Medical Research: What is the background for this study? What are the main findings?

Dr. Kalb: It’s important to evaluate the safety of biologics in the real world post-marketing setting, and in particular with respect to serious infections. We studied patients with psoriasis in the PSOLAR registry and evaluated the risk of various biologic therapies. We found that infliximab and adalimumab were associated with increased risk of serious infections when compared with non-biologic/non-methotrexate therapies, while ustekinumab and etanercept were not associated with increased risk. Continue reading

Apremilast -Otezla -May Be Cost Effective For Psoriasis Treatment

MedicalResearch.com Interview with:
Steven R. Feldman, M.D., Ph.D.

Professor of Dermatology
Wake Forest Baptist Medical Center
Winston-Salem, NC

Medical Research: What is the background for this study? What are the main findings?

Response: Results show that introducing apremilast into the treatment pathway prior to biologics is cost-saving and confers a cost and quality of life benefit. Over 10 years, apremilast was estimated to provide an additional 0.74 years (5.00 vs. 4.26 years) in which patients achieved a 75% reduction from baseline in PASI score, compared to a pathway of biologics only. It was also found to be less costly, mainly due to less time spent on more expensive biologic therapy (costs reduced by $9,072.39 over 10 years).
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Rheumatoid Arthritis: Remission Sustainable With Tapering of Biologics

Professor Paul Emery Arthritis Research UK Professor of Rheumatology Director - Leeds Musculoskeletal Biomedical Research Unit, LTHT Director – Leeds Institute of Rheumatic and Musculoskeletal Medicine University of LeedsMedicalResearch.com Interview
Professor Paul Emery
Arthritis Research UK Professor of Rheumatology
Director – Leeds Musculoskeletal Biomedical Research Unit, LTHT Director – Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds

Medical Research: What is the background for this study? What are the main findings?

Professor Emery: Joint damage and functional disability are common in people who suffer from rheumatoid arthritis (RA), even in those with early disease. We know that early aggressive treatment with biologics, such as the anti-TNF agent etanercept, results in rapid remission in many patients with moderate-to-severe rheumatoid arthritis, which can help reduce the risk of joint destruction and disability long term. However, we don’t yet know whether remission achieved with biologic therapy can be maintained after doses are reduced or therapy is withdrawn.

The PRIZE trial, a “state-of-the-art” biologic treatment trial conducted in adults with early untreated rheumatoid arthritis, was designed to fill this knowledge gap. The trial included three phases:

  • 1) induction therapy with full-dose combination etanercept-methotrexate therapy;
  • 2) maintenance therapy with a reduced-dose etanercept-methotrexate regimen, methotrexate alone, or no treatment; and
  • 3) complete treatment withdrawal. After clinical remission was induced, remission was shown to be effectively maintained with the reduced-dose combination regimen but not with the biologic-free regimens.Significantly more patients who had received the reduced-dose regimen were in remission after therapy was withdrawn than patients who received no therapy after remission induction. Interestingly, however, after remission was induced with the full-dose combination regimen, no substantial progression of joint damage on x-ray was seen in patients receiving the reduced-dose regimen, methotrexate only, or no treatment.

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Biologics Increase Incidence, Not Mortality From Opportunistic Infections

MedicalResearch.com Interview with:
Eleftherios Mylonakis, M.D., Ph.D., FIDSA
Dean’s Professor of Medical Science
Chief, Infectious Diseases Division
Alpert Medical School and Brown University

and Dr. Irene Kourbeti MD
Research Associate
Infectious Disease Division
Rhode Island Hospital, Providence, RI

MedicalResearch.com: What are the main findings of the study?

Answer : There was high quality of evidence that biologic agents are associated with increased risk of all opportunistic infections, but there was no difference in mortality attributed to the opportunistic infections. Patients receiving biologics were twice more likely to develop opportunistic infections (OIs) compared to controls (OR 1.79; 95% CI, 1.17-2.74) with a number needed to harm (NNH) of 582 patients. That means that 1 opportunistic infection  would occur in every 582 patients receiving biologics. The opportunistic infections usually occurred at the commencement of the use of the biological agent and they were not statistically more in patients with a previous exposure to anti-TNF agents as compared to the patients that had never received an anti-TNF agent..
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Rheumatoid Arthritis: Heart Disease and Biologics

MedicalResearch.com Interview with:
Lotta Ljung, MD, PhD
Umeå University, Umeå and Karolinska  Institute
Stockholm, Sweden

MedicalResearch.com: What are the main findings of the study?

Dr. Ljung:  In this observational study we observed a lower risk of acute coronary syndromes in a cohort of patients with rheumatoid arthritis (RA) exposed to tumor necrosis factor inhibitors (TNFi) compared with the risk among patients without this exposure. The adjusted relative risk (HR) was 0.73-0.82  among TNFi exposed patients compared with the biologics-naive RA cohort, depending on the time frame evaluated, which can be concluded as a moderately lower risk.

Compared with the risk in the general population, the risk in RA patients was higher, whether exposed to TNFi or not.
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Rheumatoid Arthritis: Are Two Drugs Better than One?

Dr Janet E Pope Division of Rheumatology, Department of Medicine The University of Western Ontario, St Joseph's Health Centre 268 Grosvenor Street, London, ON, Canada N6A 4V2MedicalResearch.com Interview with:
Dr. Janet E Pope
Division of Rheumatology, Department of Medicine
The University of Western Ontario, St Joseph’s Health Centre
268 Grosvenor Street, London, ON, Canada N6A 4V2

 

MedicalResearch.com: What are the main findings of the study?

 Dr. Pope: We performed a RCT of patients who were stable for 6 months of etanercept added to methotrexate (inadequate responders to Mtx) who were randomized to stopping Mtx or continuing Mtx to determine if in the next 6 months (and later as the trial continues) the response rate would be the same if Mtx was discontinued. Overall, Mtx + etanercept was not statistically equivalent to etanercept alone (ie non-inferiority did not occur); implying 6 months after stopping Mtx, the etanercept patients on monotherapy performed slightly less well than those on combination therapy.
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