Biologic Monotherapy Research Articles

Monotherapy with biologic disease-modifying anti-rheumatic drugs in rheumatoid arthritis.

Current EULAR guidelines state that biologic DMARD (bDMARD) therapy should be administered in combination with MTX or other conventional synthetic (cs) DMARD in RA. Nonetheless, a third of patients for whom a bDMARD agent is prescribed take it in the absence of concurrent csDMARD therapy. While the reasons underlying the low uptake of bDMARD-csDMARD combination therapy in clinical practice have not been well delineated, they may include poor adherence, contraindication to csDMARD therapy and adverse effects, as well as csDMARD withdrawal following remission. The challenges surrounding bDMARD therapy and the benefit/risk ratio of biologic monotherapy when compared with combination with a csDMARD will be discussed. We will provide insights into these important issues, as well as reviewing the evidence base differentiating biologic agents and exploring therapeutic options for patients with rheumatoid arthritis for whom csDMARD therapy is contraindicated or discontinued.

Precision Medicine: Maximising Treatment Benefit for Rheumatoid Arthritis Patients

This educational symposium was opened by Prof Ernest Choy, who introduced the concept of precision medicine and highlighted the importance of integrating current research with clinical experience to guide treatment decisions. He also highlighted the growing recognition of precision medicine within rheumatology. Prof Eric Ruderman then explored current medical views around the use of glucocorticoids (GCs) in rheumatoid arthritis (RA), revealing how uncertainty over the true risk/benefit ratio of these agents means that their impact as part of patient care must be further studied. Next, Prof Cem Gabay reviewed the evidence from clinical trials, registries, and real-world studies supporting biologic monotherapy as a treatment strategy in patients for whom methotrexate (MTX) is inappropriate. Prof Georg Schett then considered how current biomarker research might influence patient care in the future, especially with respect to assessing disease course and treatment responses in RA. Finally, Prof Choy presented a series of patient case studies, featuring practical issues faced by rheumatologists in the clinic, and drew upon the themes of the preceding presentations to highlight the value of a precision medicine approach to RA. Following closing remarks from Prof Choy, a lively discussion session enabled the audience to ask the expert panel about the wider clinical implications of their views. The pivotal role of IL-6 in RA5 was explored in a video at the beginning of the session, which highlighted the importance of further research in this area (available to view here).

Prevalence of biologics monotherapy in a cohort of patients with Rheumatoid Arthritis in daily clinical practice.

BackgroundReal-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy, in spite that combination therapy with Disease Modifying Drugs is more efficacious than monotherapy. The aim of our study was to assess the prevalence of biologics monotherapy in a cohort of patients with RA followed at a single center, and to analyze the reasons for monotherapy, including patients with prescriptions that do not take the medication.MethodsAll patients with Rheumatoid Arthritis, with biologic therapy followed at our Rheumatology Unit were included. Prevalence and reasons for biologics monotherapy was calculated in general, for each biologic course and for each biologic. Prescription data was obtained from the Electronic Medical Record, and drugs acquisition was obtained from the Hospital Administrative database. Drug survival was also calculated and compared between monotherapy and combination therapy.ResultsSeventy nine patients with 115 courses of biologic treatments were included. In 40 (35 %, 95 % CI: 26–44 %) of all biologics courses, biologics were initiated as monotherapy. In 27 courses (23 %, 95 % CI: 16–32 %) biologic monotherapy was prescribed by the treating rheumatologists, and in the other 13 (11 %, 95 % CI: 6–18 %) it was initiated as such by decision of the patient regardless of the physician indication. Reasons for prescription of biologic monotherapy by the treating rheumatologists were adverse events with previous DMARDs in 55.5 %, and was not specified in the remaining courses. Only 25 % of biologics’ courses were monotherapy from the beginning to the end of the biologic therapy. The overall survival on biologics was 45 % (95 % CI: 35–55 %) at 3 years. There were no statistically differences in biologics survival by modality (monotherapy vs combination) (p = 0.543), course (p = 0.4454), or by biologic drug (p = 0.9612).ConclusionsAlmost 1/3 of patients on biologics use them as monotherapy. This is due to physician’s preferences in 60 % of the cases, and to patients not compliance with the indication in around 40 % of the cases. Better communications is needed to assure that physicians and patients agree on the prescribed and used medication.

Comparative effectiveness of biologic monotherapy versus combination therapy for patients with psoriatic arthritis: results from the Corrona registry

ObjectivesTo characterise the comparative effectiveness of combination therapy (a tumour necrosis factor inhibitor (TNFi) and a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate) and monotherapy (TNFi only) for...

Combined Immunosuppression Impairs Immunogenicity to Tetanus and Pertussis Vaccination Among Patients with Inflammatory Bowel Disease.

Pertussis epidemics have recently emerged across the United States, prompting broad public health recommendations for adult Tdap vaccination (tetanus, diphtheria, acellular pertussis). The impact of immunosuppressive regimens for inflammatory bowel disease (IBD) on vaccine responses to the Tdap vaccine is not known. We performed a prospective controlled trial between April 2011 and March 2012. Adults with IBD were consecutively stratified based on therapeutic regimen into one of 5 groups: A: no IBD therapy or 5-aminosalicylates alone; B: maintenance biologic monotherapy; C: maintenance immunomodulator monotherapy; D: combined biologic and immunomodulator therapy; and E: healthy age-matched controls. Subjects received Tdap, and serum antibody levels against tetanus toxoid, pertussis toxoid, and filamentous hemagglutinin (FHA) were drawn just before and approximately 4 weeks after vaccination. The primary outcome was the booster response rate to each antigen. Secondary outcomes included the differences in pregeometric and postgeometric mean titers. A total of 98 subjects enrolled, and 84 completed the study. Tetanus response rates were 55%, 56%, 40%, 27%, and 63% across groups A to E, respectively. Group D rates were lower than those of group B (P = 0.02). Postvaccination pertussis toxoid responses were 59%, 72%, 47%, 45%, and 75%, while FHA responses were 86%, 72%, 80%, 64%, and 75% across groups A to E, respectively. Prevaccination and postvaccination geometric mean titer differences for FHA were lower in group D than those in group A (P = 0.05). Antibody responses to tetanus and pertussis vaccination may be affected by therapeutic drug regimen. Patients with IBD should optimally receive Tdap before starting immunomodulators, particularly when used in combination with anti-tumor necrosis factor alpha agents.

Effectiveness and drug adherence of biologic monotherapy in routine care of patients with rheumatoid arthritis: a cohort study of patients registered in the Danish biologics registry.

To estimate the prevalence of Danish RA patients currently on biologic monotherapy and compare the effectiveness and drug adherence of biologic therapies applied as monotherapy. All RA patients registered in the Danish biologics database (DANBIO) as receiving biologic DMARD (bDMARD) treatment as monotherapy without concomitant conventional synthetic DMARDs (csDMARDs) during the study period 1 May, 2011 through 30 April 2013 were eligible for inclusion. All patient files were checked to ensure that they were in accordance with the treatment registration in DANBIO. Descriptive statistics for prevalence, effectiveness and drug adherence of bDMARD monotherapy were calculated. Of the 775 patients on bDMARD monotherapy, adalimumab (21.3%), etanercept (36.6%) and tocilizumab (15.3%) were the most prevalent biologic agents administered. At the 6-month follow-up, the overall crude clinical disease activity index remission rate in patients still on a biologic drug was 22%, the 28-joint DAS remission rate was 41% and the response rate of those with a 50% improvement in ACR criteria was 28%. At the 6-month follow-up, the drug adherence rates were similar for the different bDMARDs, with the exception of infliximab, which had significantly poorer drug adherence (P < 0.001). The overall drug adherence (except for infliximab) was approximately 70% after 2 years. Nearly one in five (19%) biologic treatments for RA was prescribed in Denmark as monotherapy, of which 70% were on monotherapy from bio-initiation and 30% were on monotherapy after cessation of a concomitant csDMARD. Acceptable drug adherence and remission rates were achieved with bDMARDs. With the exception of infliximab, no statistically significant differences were observed between anti-TNFs and biologics with other modes of action.

Biologic monotherapy in the treatment of rheumatoid arthritis.

Biologics, possibly in combination with a conventional disease-modifying antirheumatic drug (DMARD) – preferably methotrexate (MTX), are used in accordance with the recommendations of the international rheumatological societies. However, in clinical practice, this recommendation is often problematic, as many rheumatologists know from personal experience. The quality of life of the patient is affected mainly by drug-induced intolerances (eg, MTX). Thus, the acceptance of the patient to treatment is often so inadequate that a discontinuation of the drug is necessary. In daily practice, approximately 30% of patients with biological therapy receive no concomitant DMARD according to the register data.

Cost-utility analysis of tocilizumab monotherapy in first line versus standard of care for the treatment of rheumatoid arthritis in Greece.

The study aims to evaluate the cost-effectiveness of adding tocilizumab (TCZ) first line to a treatment sequence for patients with active rheumatoid arthritis (RA), who had an inadequate response to one or more traditional synthetic disease-modifying antirheumatic drugs (DMARDs) and are intolerant to methotrexate (MTX), or in whom continued treatment with MTX is considered inappropriate. An individual simulation model was applied to project lifetime costs and outcomes for 10,000 patients from a payer's perspective. The analysis compared the standard treatment pathway (STP) with a similar pathway, where treatment was initiated with TCZ. QALYs were used as primary efficacy outcomes. Efficacy data were obtained from the ADACTA trial and a network meta-analysis. Clinical practice standards were derived from an expert panel of Greek rheumatologists. Results indicate that a treatment sequence starting with TCZ yields 1.17 more QALYs (9.38 vs. 8.21) at an additional cost of €3,744 (€119,840 vs. €86,096) compared with the STP. The incremental cost-effectiveness ratio was €28,837/QALY gained. Probabilistic sensitivity analysis confirms robustness of these findings as consistently below a threshold of €45,000. The results of the analysis suggest that TCZ, when used as a first-line biologic monotherapy, can be a cost-effective treatment option for the management of active RA in patients in need of biologic monotherapy.

Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents.

Characteristics Associated with Biologic Monotherapy Use in Biologic-Naive Patients with Rheumatoid Arthritis in a US Registry Population.

IntroductionThe aim of this study was to describe factors associated with initiating a biologic as monotherapy vs in combination with a conventional disease-modifying antirheumatic drug (DMARD) in biologic-naive patients with rheumatoid arthritis (RA) enrolled in the Corrona registry.MethodsFirst biologic initiations were classified as monotherapy (Bio MT) or combination therapy (Bio CMB). Baseline demographic and clinical characteristics were evaluated. Odds ratios (OR) based on mixed effects regression models estimated the association of covariates and use of monotherapy. Median odds ratios (MOR) based on estimated physician random effects quantified variation in individual physician use of monotherapy.ResultsBetween October 2001 and April 2012, 3,923 previously biologic-naive patients initiated biologic therapy, of which 19.1 % initiated as monotherapy. Baseline characteristics of patients initiating Bio MT and Bio CMB were similar for age, sex, duration of RA, and clinical disease activity index. Significantly higher proportions of Bio CMB initiators had prior conventional DMARD (97.23 vs 85.60 %; P < 0.01) and methotrexate (MTX) use (91.68 vs 71.87 %; P < 0.01) compared with Bio MT initiators. Variation in individual physician use of monotherapy [MOR 1.89; 95 % confidence interval (CI), 1.66–2.23] and use of biologics approved by the United States Food and Drug Administration for monotherapy (OR 1.47; 95 % CI, 1.20–1.81) significantly influenced the odds of initiating Bio MT. Patient history of hepatic disease, neutropenia, and malignancy were associated with increased odds of being prescribed Bio MT.ConclusionIn addition to regulatory approval for monotherapy and specific pre-existing comorbidities, significant variation in physician use of monotherapy was associated with increased likelihood of initiating Bio MT, independent of patient factors.Electronic supplementary materialThe online version of this article (doi:10.1007/s40744-015-0008-9) contains supplementary material, which is available to authorized users.

Anti-TNF-alpha loss of response is associated with a decreased percentage of FoxP3+ T cells and a variant NOD2 genotype in patients with Crohn's disease.

Anti-TNF-α therapies interact with the tolerogenic response in patients with Crohn's disease, modulating inflammation. However, drug levels and the genetic background may affect this interaction. Patients with Crohn's disease in remission on biologic monotherapy were enrolled in this study. FoxP3+ lymphocytes, NOD2 genotype, serum cytokine, anti-TNF-α levels, and anti-drug antibodies were evaluated. Regulatory T cell response to infliximab was evaluated in vitro. Fifty-seven patients were included. Thirty-nine patients (68.4%) were receiving non-intensified biologic therapy whereas 18 patients (31.6%) were under an intensified biologic schedule due to loss of response. Eleven intensified patients (61.1%) showed a variant NOD2 genotype vs 9 on non-intensified biologics (23%, p < 0.01). Percentage of FoxP3+ T cells and serum free anti-TNF-α levels were significantly higher in patients with a wild-type vs variant NOD2 genotype, either under non-intensified or intensified schedule. Increasing amounts of infliximab significantly increased the expression of FoxP3+ T cells and anti-TNF-α levels in the supernatant from wild-type NOD2 patients cultured cells whereas the induction of FoxP3+ T cells and anti-TNF-α levels in the supernatant from variant NOD2 patients cultured cells were significantly lower. TNF-α and IL-10 showed a correlation with the FoxP3+ T cell population percentage and serum levels of anti-TNF-α, irrespective of NOD2 genotype. Eight variant NOD2 patients (66.6%) vs 4 wild-type NOD2 patients (8.8%) showed a perianal phenotype (p = 0.01). A significant reduction of the percentage of FoxP3+ T cells and serum levels of anti-TNF-α was observed in patients with the associated perianal disease. Anti-TNF-α loss of response is associated with a decreased percentage of FoxP3+ T cells and a variant NOD2 genotype in patients with CD.

PMS87 - Comparison of Clinical Characteristics of Patients With Rheumatoid Arthritis (Ra) Receiving Biologic Monotherapy and Biologic-Containing Combination Therapy in Europe

PMS87 - Comparison of Clinical Characteristics of Patients With Rheumatoid Arthritis (Ra) Receiving Biologic Monotherapy and Biologic-Containing Combination Therapy in Europe

AB0409 Treatment Pathways for Adults with Inflammatory Arthritis Receiving Biologic Therapy at an NHS Tertiary Referral Centre

BackgroundAlthough much research has been done into factors influencing selection of biological therapies, there is a paucity of real-world data on the choices made by clinicians and the treatment pathways...

SAT0065 Effectiveness and Drug Adherence of Biologic Monotherapy in Danish Rheumatoid Arthritis Patients: A Cohort Study of Clinical Practice in the Danbio Registry

BackgroundConcurrent use of methotrexate (MTX) and a biologic is generally the standard-of-care in patients with RA who have disease activity despite MTX. It has been estimated that between 10 and...

FRI0177 Biologic Drug Initiators: Real World Patterns of Monotherapy and Combination Therapy after One Year

BackgroundLittle is known regarding the treatment practices of rheumatologists with respect to biologic initiation as monotherapy versus combination therapy with nonbiologic disease modifying anti-rheumatic drugs (nbDMARDs) such as methotrexate (MTX)....

SAT0236 Maintenance and Efficacy of Abatacept Monotherapy Compared to Abatacept + Conventional Synthetic DMARD in Patients with Rheumatoid Arthritis: Data from ORA Registry

BackgroundClinical trials performed in RA patients with anti-TNFa therapy lead to demonstrate the superiority of DMARDs association strategy over biologic monotherapy. Accordingly, the association Methotrexate-bioDMARD became the gold standard of...

FRI0068 Use of Biologic Monotherapy among Rheumatoid Arthritis Patients: Investigating Clinical Drivers for Treatment Choice

BackgroundEULAR guidelines for the treatment of rheumatoid arthritis (RA) patients (pts) using biological disease-modifying antirheumatic drugs (bDMARD) state that these should be combined with methotrexate (MTX) or other conventional synthetic...

FRI0293 Characteristics of Patients with Rheumatoid Arthritis Treated with Biologic Therapy as Monotherapy

BackgroundThe treatment for Rheumatoid Arthritis (RA) is based mainly on the use of synthetic or biological DMARDs. Most current guidelines recommend the use of biologics in combination with MTX as...

FRI0307 Persistency and Its Predictors of Biologic Monotherapy in Patients with RA: Analyses from the Corrona RA Registry

BackgroundInternational task forces recommend conventional disease-modifying antirheumatic drugs (DMARDs) as first-line therapy in patients (pts) with rheumatoid arthritis (RA).1,2 In some pts, treatment with a biologic DMARD as monotherapy (MT)...

FRI0294 Biologic Monotherapy: A Treatment Option for Elderly RA Patients with Multimorbid Conditions

BackgroundThe treatment of RA with biologic (b)DMARDs should usually be combined with the non-biologic (nb)DMARD methotrexate (MTX). Randomized controlled trials showed superior efficacy of combination therapy in RA patients. Nevertheless,...