anti-TNF Monotherapy Research Articles

Addition of thiopurines can recapture response in patients with Crohn's disease who have lost response to anti‐tumor necrosis factor monotherapy

Anti-tumor necrosis factor (TNF) antibodies are effective in maintaining remission in Crohn's disease. However, a significant proportion of patients lose response to these agents with time. This study aimed to determine whether the introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy results in regained response. Five patients (four males; aged 22-38 years) with active Crohn's disease, who had an initial response to anti-TNF therapy but had lost response, were commenced on azathioprine or mercaptopurine at standard doses while continuing anti-TNF therapy. All had previously failed thiopurine therapy prior to starting anti-TNF treatment. All patients experienced improved clinical symptoms within 2-6 months, with benefit sustained over a mean follow-up of 19 months. Two patients with an elevated C-reactive protein at the time of thiopurine addition demonstrated a fall in C-reactive protein. Colonoscopy before and after thiopurine addition in four patients showed improvement in all, with mucosal healing achieved in two. No adverse effects of treatment were noted. Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.

SAT0047 Impact of Anti-Rheumatic Treatment on Immunogenicity of Pandemic H1N1 Influenza Vaccine in Patients with Arthritis

BackgroundA monovalent, adjuvanted, inactivated H1N1 influenza vaccine (Pandemrix) was reported as highly immunogenic resulting in seroconversion in 77-94% of adults after administration of a single dose (ref).ObjectivesTo investigate impact of...

AB0351 Vaccination against hepatitis B in patients with rheumatoid arthritis (RA). Preliminary results with double-dose

BackgroundIn recent years the different drug treatments in rheumatic patients can lead to situations of immunosuppression associated with an increased risk of infection by immunization.ObjectivesTo present preliminary results of vaccination...

AB0352 Vaccination against hepatitis B in patients with psoriatic arthritis (PA). Preliminary results with double dose schedule

BackgroundThe different drug treatments in rheumatic patients can lead to situations of immunosuppression and predispose to infection by immunization.ObjectivesTo present preliminary results of antibody response of immunisation with a double-doses...

Persistence of antibody response 1.5 years after vaccination using 7-valent pneumococcal conjugate vaccine in patients with arthritis treated with different antirheumatic drugs

IntroductionThe aim of this study was to explore the persistence of an antibody response 1.5 years after vaccination with 7-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis (RA) or spondyloarthropathy (SpA) treated with different antirheumatic drugs.MethodsOf 505 patients initially recruited, data on current antirheumatic treatment and blood samples were obtained from 398 (79%) subjects after mean (SD, range) 1.4 (0.5; 1 to 2) years. Antibody levels against pneumococcal serotypes 23F and 6B were analyzed by using enzyme-linked immunosorbent assay (ELISA). Original treatment groups were as follows: (a) RA receiving methotrexate (MTX); (b) RA taking anti-TNF monotherapy; (c) RA taking anti-TNF+MTX; (d) SpA with anti-TNF monotherapy; (e) SpA taking anti-TNF+MTX; and (f) SpA taking NSAID/analgesics. Geometric mean levels (GMLs; 95% CI) and proportion (percentage) of patients with putative protective antibody levels ≥1 mg/L for both serotypes, calculated in different treatment groups, were compared with results 4 to 6 weeks after vaccination. Patients remaining on initial treatment were included in the analysis. Possible predictors of persistence of protective antibody response were analysed by using logistic regression analysis.ResultsOf 398 patients participating in the 1.5-year follow up, 302 patients (RA, 163, and SpA, 139) had unchanged medication. Compared with postvaccination levels at 1.5 years, GMLs for each serotype were significantly lower in all groups (P between 0.035 and <0.001; paired-sample t test), as were the proportions of patients with protective antibody levels for both serotypes (P < 0.001; χ2 test). Higher prevaccination antibody levels for both serotypes 23F and 6B were associated with better persistence of protective antibodies (P < 0.001). Compared with patients with protective antibody levels at 1.5 years, those not having protective antibody levels were older, more often women, had longer disease duration and higher HAQ and DAS, and had a lower proportion of initial responders to both serotypes.Concomitant anti-TNF treatment and MTX were identified as negative predictors of the persistence of protective antibodies among RA patients (P = 0.024 and P = 0.065, respectively). Only age 65 years or older (P = 0.017) and not antirheumatic treatment was found to be a negative predictor of protective antibodies in patients with SpA.ConclusionsAfter initial increase, 1.5 years after pneumococcal vaccination with 7-valent conjugate vaccine, postvaccination antibody levels decreased significantly, reaching levels before vaccination in this cohort of patients with established arthritis treated with different antirheumatic drugs. MTX and anti-TNF treatment predicted low persistence of protective immunity among patients with RA. To boost antibody response, early revaccination with conjugate vaccine might be needed in patients receiving potent immunosuppressive remedies.Trial registration numberEudraCT EU 2007-006539-29 and NCT00828997.

PMS75 Real-World Utilization Patterns of Rheumatoid Arthritis Medications in the United States: Anti-TNF Monotherapy and Adherence With Non-Biologic DMARDs in Combination with Anti-TNF Therapy

PMS75 Real-World Utilization Patterns of Rheumatoid Arthritis Medications in the United States: Anti-TNF Monotherapy and Adherence With Non-Biologic DMARDs in Combination with Anti-TNF Therapy

Setting priorities for comparative effectiveness research in inflammatory bowel disease: Results of an international provider survey, expert rand panel, and patient focus groups

Comparative effectiveness research (CER) is an emerging field that compares the relative effectiveness of alternative strategies to prevent, diagnose, or treat patients who are typical of day-to-day practice. We developed a priority list of CER topics for inflammatory bowel disease (IBD). Following the Institute of Medicine's approach, we developed and administered a survey to gastroenterologists asking for important CER topics in IBD. Two patient focus groups were convened to solicit additional CER studies. CER topics were presented to the expert panel using the RAND/UCLA methodology. Following initial ratings, the panel met to discuss and re-rate priorities. The top 10 CER topics were identified using a point-allocation system. Responses were collated into 234 CER topics across 21 categories, of which 87 were prioritized for discussion and re-rated. Disagreement regarding priorities was observed in 5 of 87 studies. We utilized a point-allocation system to prioritize the top-10 CER topics. These related to comparing the effectiveness of: biomarkers in IBD; withdrawal of anti-tumor necrosis factor (TNF) or immunomodulators for Crohn's disease in remission; mucosal healing as an endpoint of treatment; infliximab levels versus standard infliximab dosing; anti-TNF monotherapy versus combination therapy in patients failing thiopurines; safety of long-term treatment options; anti-TNF versus thiopurines for prevention of postoperative recurrence; and treatment options for steroid-refractory UC. We systematically developed a list of high-priority IBD topics for CER based on a survey of gastroenterologists, expert review, and patient input. This list may guide IBD research toward the most important CER studies.

Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial

The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6–8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.

Etanercept (ETN) with methotrexate (MTX) is better than ETN monotherapy in patients with active rheumatoid arthritis despite MTX therapy: a randomized trial

The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6-8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.

PWE-032 Audit of prevention of opportunistic infections in immunosuppressed patients with inflammatory bowel disease: how close are we to the European Crohn's and Colitis Organisation guidelines?: Abstract PWE-032

Introduction The European Crohn's and Colitis Organisation (ECCO) has recently published recommendations on screening and prevention of opportunistic infections in inflammatory bowel disease (IBD) patients. These are based on expert opinion and available evidence, and are more extensive than previous guidelines. The aim of this audit is to compare current practice of screening for, and prevention of, opportunistic infections in our IBD clinic, with these recommendations, and to examine the implications of following the guidelines. Methods IBD patients at risk of opportunistic infections (as defined by ECCO; those treated with thiopurines, methotrexate, anti-TNF or prednisolone>20 mg daily for >2 weeks) were selected consecutively from our IBD clinic and infliximab infusion service from July to November 2009. A data collection sheet was completed for each patient by direct questioning in clinic and by review of patients' records. Information collected included; demographic and clinical details, immunosuppressive medication (IM), screening tests performed (HBsAg, anti-HBs, antiHBc, HCVAb, HIVAb, VZVAb (not applicable (n/a) if history of VZV infection), CXR and cervical smear (females)), and vaccinations given prior to treatment (Hepatits B, VZV (n/a if history of VZV infection), HPV (women<26 years), influenza and Streptococcus pneumoniae). A cost analysis of this screening and vaccination strategy was performed. Results Ninety patients (Crohn's disease (n=70), Ulcerative Colitis (n=19), IBD-unclassified (n=1)) were audited to the time of abstract submission. Of these, 46 were male and 44 female (median age 32 years). Forty-one percent of patients were taking thiopurine monotherapy, 34% concomitant thiopurine and anti-TNF therapy, 14% anti-TNF monotherapy, 6% prednisolone, and 5% methotrexate. The proportion of patients who had recommended screening tests and vaccinations are shown in the table. Patients on anti-TNF therapy were more likely to have undergone CXR, hepatitis B and C screening (p<0.05). The cost of these screening tests and vaccinations (excluding HPV) was GBP£255 per patient (equipment and manpower costs not included) ([Abstract 032][1]). View this table: Abstract PWE-032 Screening tests and vaccinations performed Conclusion Our current practice of screening for and prevention of opportunistic infections in at-risk IBD patients is not in line with recent ECCO recommendations. However, some of the ECCO recommendations are based on limited evidence. Therefore, ongoing audit and research, as well as proof of cost benefit, may be required before they gain widespread acceptance. [1]: #T1

CD11c as a Transcriptional Biomarker to Predict Response to Anti-TNF Monotherapy With Adalimumab in Patients With Rheumatoid Arthritis

We performed transcription profiling using monocytes to identify predictive markers of response to anti-tumor necrosis factor (anti-TNF) therapy in patients with rheumatoid arthritis (RA). Several potential predictors of response were identified, including CD11c. Validation in samples from independent cohorts (total of n = 27 patients) using reverse transcription-PCR confirmed increased expression of CD11c in responders to adalimumab (100% sensitivity; 91.7% specificity, power 99.6%; alpha = 0.01). Pretherapy CD11c levels significantly correlated with the response criteria as defined by the American College of Rheumatology (ACR) (r = 0.656, P < 0.0001). However, CD11c was neither predictive of response to methotrexate (MTX) alone (n = 34) nor to MTX in combination with adalimumab (n = 16). Clinical responders revealed a reset to a normal expression pattern of resident/inflammatory monocyte markers, which was absent in nonresponders. Therefore, an analysis of key cell types identifies potentially predictive biomarkers that may help to restrict the use of adalimumab to therapy responders. Larger studies, including studies of monotherapy with other drugs, are now needed to confirm and validate the specificity of CD11c for anti-TNF biologics.

Tratamiento de inicio en la artritis reumatoide con tratamientos biológicos. Postura a favor

Changes in diagnosis and treatment of rheumatoid arthritis oblige us to question clinical practice. Evidence demonstrates that the combination of biologics and methotrexate in rapid increments leads to larger remission rates than methotrexate alone. The combination has a faster clinical response in activity, physical function, quality of life, fatigue and sleep. But the most significant effect of biologics is on radiographic progression. The reduction in radiological damage has a spectrum that goes from anti-TNF+methotrexate to anti-TNF monotherapy, being less with methotrexate, and independent from improvement in activity; it occurs with all of the anti-TNF drugs and with other targets with different mechanisms of action (anti-CD20, T cell costimulation inhibitors and anti IL-6). The clinical significance of this finding will be seen in the future, when more is known of its impact on the poor outcomes of RA patients. Because methotrexate is an excellent drug, it seems madness to say that all patients should receive biologics+methotrexate, but it is reasonable to consider that a subgroup must receive them from the start. The American College of Rheumatology recommends their use in patients with RA of less than 6 months since onset, with no previous exposure to methotrexate, persistent and elevated activity (<3 months) and poor prognostic factors or those with persistent and elevated activity (3–6 months) independent of poor prognostic factors, and if the patient “has insurance”. A final thought would be: Is there a new treatment pyramid which has cost at its base now?