A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK Inhibitor Therapy Across Four Common Inflammatory Indications in Adult US Managed Care Patients

Introduction

Biologic therapies are used to treat several inflammatory diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Data from a commercial claims database were used to evaluate utilization and cost of biologic treatment for these conditions.

Methods

Data were obtained from the Optum Research Database. Patients were aged 18–63 years with diagnosis of moderate to severe RA, PsO, PsA, and/or AS and first (index) claim for biologics abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab or non-biologic tofacitinib between March 1, 2011 and February 28, 2013. One-year treatment costs were based on observed paid amounts and used to impute dosing. Treatment patterns (persistence, switching, discontinuing, restarting) were evaluated.

Results

Data from 20,159 patients were analyzed for index medications abatacept (n = 583), adalimumab (n = 6521), certolizumab pegol (n = 415), etanercept (n = 9116), golimumab (n = 231), infliximab (n = 1906), rituximab (n = 295), tocilizumab (n = 165), ustekinumab (n = 922), and tofacitinib (n = 5). For patients with RA only, costs were lowest for tofacitinib ($18,769), rituximab ($19,569), or abatacept ($21,877), and ranged from $23,682 to $30,269 for all other medications. For patients with PsO only, costs were lowest for adalimumab ($29,186), etanercept ($31,212), and infliximab ($32,409) compared with ustekinumab ($53,746). For patients with PsA only, costs were lowest for etanercept ($26,916), followed by golimumab ($27,987), adalimumab ($28,749), and infliximab ($31,974). Costs were lowest with etanercept for RA plus PsA ($25,477) and for PsO plus PsA ($29,376), and with golimumab for AS only ($24,225). Across indications, annual costs were $29,521, $27,488, and $28,672 for adalimumab, etanercept, and infliximab, respectively; persistence was greatest with infliximab (range 66–79%) compared with 11–59% for all other biologics.

Conclusion

One-year treatment costs varied considerably between medications and indications. Some newly approved agents had lower costs but further research is needed to confirm these estimates as more patients are treated.

Funding

Immunex (a wholly owned subsidiary of Amgen Inc.) and Wyeth (acquired by Pfizer).

     

Indirect comparison of biological treatments in refractory rheumatoid arthritis

What is known and Objective: A number of biological treatments are available for rheumatoid arthritis. They are effective some patients but their comparative efficacy is inadequately evaluated. Our aim was to compare the efficacy of adalimumab, etanercept, infliximab, abatacept, tocilizumab, golimumab and certolizumab pegol in rheumatoid arthritis, refractory to disease‐modifying antirheumatic drugs (DMARDs), through a systematic review of published trials. Methods: As there were no direct comparisons, we searched for studies with similar characteristics to identify trials with results suitable for indirect comparison. Randomized, placebo‐controlled pivotal clinical trials, with reported American College of Rheumatology ACR50 data at 24/30 weeks as efficacy endpoint, approved clinical doses and patients resistant to DMARDs who had not previously received other biological treatments were included. ACR50 was defined as the primary endpoint for the indirect comparison, with ACR20 and ACR70 as secondary endpoints. When two or more trials on one same drug were available, and a combined analysis was performed when appropriate. In the indirect comparison, the Bucher adjusted method was used with etanercept as reference drug. In the equivalence study, the equivalence window was a response efficacy difference of 15% between the alternatives. Results and Discussion: Ten trials were found suitable for detailed analysis. In the clinical trials, all the biological drugs were seen to be more effective than placebo. Indirect comparison based on the ACR50 efficacy criterion all biological treatments showed similar results within the defined equivalence Δ value. The absolute efficacy difference (reduction of absolute risk, RAR) versus etanercept being 2·6% with adalimumab, 14% with infliximab, 11·6% with abatacept, 3% with tocilizumab, 12·4% with golimumab and 6·5% with certolizumab pegol. What is new and Conclusion: The biological drugs used in rheumatoid arthritis are no different in efficacy. Their therapeutic positioning depends on their relative safety and convenience profiles.     

Comparative Efficacy of Biologic Therapy in Biologic-Naïve Patients With Crohn Disease: A Systematic Review and Network Meta-analysis

ObjectiveTo study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD).Patients and MethodsWe conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach.ResultsWe identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%).ConclusionOn the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.     

Economical aspect of biological therapy in inflammatory conditions in Hungary

Introduction: There has been a burst in the use of biological therapies in the past decade resulting in increasing costs. In 2006 – 2010 the following biological agents were available in Hungary: adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab, and ustekinumab. All biological agents except rituximab were first line therapies; rituximab was a second line option in rheumatoid arthritis.

Areas covered: Data of the financing system related to health care services from the data warehouse of the Hungarian National Health Insurance Fund were in inflammatory conditions. Our analysis showed a constant increase in number of patients and overall cost of biological therapy as well as annual cost of biological agents. Distribution of first choice of biological therapy was compared in different diseases. Time from diagnosis to start of biological therapy showed relatively high deviations.

Expert opinion: In order to achieve both health benefit and cost-effectiveness it is crucial that biological therapy is initiated early enough in the course of the disease, after the failure of non-biological therapies. Health authorities in close collaboration with clinical decision-makers should ensure that early detection of the disease and early initiation of appropriate therapies—including non-biological and biological therapies—are carried out in the health care systems.     

Natalizumab in the treatment of Crohn’s disease patients

Introduction: Amongst the available therapies for moderate to severe Crohn’s disease (CD) patients who are refractory to conventional therapy, anti-TNF blockers are the most effective biological treatment option. However, many patients experience a primary or secondary non-response to anti-TNF therapy, creating the need for alternative biological drugs that target different mechanisms of action and inflammatory pathways. Natalizumab, the first non-anti-TNF biological drug to be approved for treatment of CD patients, is a recombinant humanized antibody that targets the α₄-subunit of both α₄β₁ and α₄β₇ integrins, thus preventing activated leukocyte homing to the intestinal mucosa.

Areas covered: This article summarizes the pathophysiological background and the efficacy and safety data of natalizumab, as well as the regulatory issues surrounding it.

Expert opinion: Natalizumab represents an effective therapy for refractory CD patients. However, the rare but serious event of progressive multifocal leukoencephalopathy occurrence has compromised its widespread use. The subsequent advent of more specific anti-integrin drugs (i.e. vedolizumab) that carry a more favorable safety profile further reduces the clinical indications for natalizumab. The regulatory process for natalizumab distribution and monitoring in the US may provide a forum for discussion on how to optimally manage use of drugs that offer clinical benefits to patients, while minimizing associated risks.     

Novel approaches to biological therapy for psoriatic arthritis

ABSTRACT

Introduction: Improved understanding of the immunopathogenic mechanisms in psoriatic arthritis (PsA) has led to the development of targeted biological therapies, which demonstrate superior clinical efficacy to traditional disease-modifying antirheumatic drugs (DMARDs). There are currently 3 classes of biological agents that are approved for the treatment of psoriatic disease: tumor necrosis factor alpha inhibitors (TNFi), including etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol; ustekinumab, a monoclonal antibody (mAb) directed against interleukin (IL)-12 and IL-23; and secukinumab, a human anti-IL-17A mAb. Other agents are in development. Our growing experience with these medications has revolutionized the approach to disease management in PsA.

Areas covered: This article discusses the rationale for using biological therapies in PsA, highlighting clinical trial evidence that supports the use of these agents. We summarize novel treatment approaches using biological therapies in the management of PsA, including early intervention, targeted therapy, TNFi switching, combination therapy, and tapering or discontinuation of biological therapy. We conclude with a discussion of the importance comorbidities have on selection of therapy.

Expert opinion: The advent of highly effective biological therapies has revolutionized the management of patients with PsA. Growing experience with these agents has led to novel treatment approaches that may improve clinical outcomes for PsA patients.     

Population Pharmacokinetics and Exposure–Response Modeling of Golimumab in Adults With Moderately to Severely Active Ulcerative Colitis

PurposeGolimumab is a fully human monoclonal antibody to tumor necrosis factor-α and is indicated for the treatment of moderately to severely active ulcerative colitis (UC). This study analyzed the population pharmacokinetic (PK) properties of golimumab and exposure–response for efficacy and safety, using data from combined Phase II/III UC studies.MethodsData on serum golimumab concentration following IV and subcutaneous (SC) administration were fitted simultaneously using nonlinear mixed-effects modeling for the development of a population PK model. Logistic regression models were used for assessing relationships between serum golimumab concentrations and clinical efficacy outcomes in SC induction and maintenance studies. The percentages of patients developing infections, serious infections, and serious adverse events were assessed by golimumab exposure metric quartiles.FindingsThe PK properties of golimumab are well described by a 2-compartment model with first-order absorption and elimination. Typical values of PK parameters in a 70-kg patient were clearance, 0.544 L/d; central and peripheral compartment V_d, 3.43 and 2.27 L, respectively; and intercompartmental clearance, 0.291 L/d. Golimumab t_1/2 was 10.5 days; bioavailability following SC administration was 52.2%. Body weight, anti-golimumab antibodies, serum albumin, C-reactive protein, and alkaline phosphatase affected golimumab disposition. A positive exposure–response relationship was established between golimumab concentration and efficacy outcomes. No apparent correlation between golimumab exposure and rate of infections, serious infections, or serious adverse events was observed in patients receiving golimumab 50 or 100 mg SC every 4 weeks through 1 year.ImplicationsBody weight, serum albumin, and anti-golimumab antibodies explain some of the variability observed in the PK properties of golimumab, and exposure–response findings support the recommended posology of golimumab in UC. ClinicalTrials.gov identifiers: NCT00488774, NCT00487539, and NCT00488631.     

Cost Per Responder Associated with Biologic Therapies for Crohn’s Disease, Psoriasis, and Rheumatoid Arthritis

Introduction

Biologic therapies have demonstrated efficacy and safety in several chronic systemic disorders. The authors indirectly compared response rates and costs per responder associated with biologic treatments for moderate-to-severe Crohn??s disease (CD), psoriasis (Ps), and/or rheumatoid arthritis (RA).

Methods

A systematic literature search was performed to identify phase 3 randomized controlled trials of biologics for CD (adalimumab, infliximab), Ps (adalimumab, etanercept, infliximab, ustekinumab 45 mg, ustekinumab 90 mg), or methotrexate-refractory RA (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab). Food and Drug Administration-approved dosing schedules were evaluated. Published response rates were extracted, with response defined in CD, Ps, and RA as: ??70-point reduction in CD Activity Index at 12 months; ??75% improvement in Psoriasis Area and Severity Index at 3 months; and ??50% improvement in American College of Rheumatology component scores at 6 months. Within each indication, mixed-treatment comparison meta-analyses were conducted to derive pooled estimates and 95% CIs of response rate difference versus placebo for each biologic, adjusting for cross-trial variation in control-arm response rates. Cost per responder was estimated for each biologic as projected per patient drug costs (2011 US$) divided by response rate difference.

Results

Altogether, 23 publications were selected. In CD, 12-month cost per responder was estimated at $116,291 (95% CI $71,637?C208,348) for adalimumab and $125,169 (95% CI $60,532?C267,101) for infliximab. Among biologics approved in Ps, 3-month cost per responder was lowest for adalimumab ($9,756; 95% CI $8,668?C11,131), infliximab ($12,828; 95% CI $11,772?C13,922), and ustekinumab 45 mg ($13,821; 95% CI $12,599?C15,167). In RA, biologics with the lowest 6-month cost per responder were adalimumab ($27,853; 95% CI $19,284?C40,270), etanercept ($29,140; 95% CI $14,170?C61,030), and tocilizumab ($31,363; 95% CI $14,713?C64,232).

Conclusion

Meta-analyses of clinical trials found considerable variation in cost-effectiveness of biologic therapies for CD, Ps, and RA. These results may help determine biologic utilization in these chronic diseases.     

Treatment Patterns in the First Year After Initiating Tumor Necrosis Factor Blockers in Real-World Settings

Background

Tumor necrosis factor (TNF)-blockers are approved for use in several immune-related conditions, but treatment patterns, such as switching between TNF blockers or restarting treatment after a gap in therapy, are not clearly established. This analysis examined TNF blocker treatment patterns within the first year after initiating treatment with etanercept, adalimumab, or infliximab in patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis.

Methods

Administrative claims data from the MarketScan? Commercial Claims and Encounters Database (Thomson Reuters, Ann Arbor, MI, USA) were analyzed for patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who were continuously enrolled and newly initiated etanercept, adalimumab, or infliximab treatment between January 1, 2005 and July 1, 2009. Persistence (no treatment gap ??45 days), restarting index therapy (after a ??45-day treatment gap), switching to a different biologic of interest (certolizumab, golimumab, ustekinumab, alefacept, abatacept, rituximab, or tocilizumab), and stopping (??45-day treatment gap with no restart or switch) were analyzed for the first year after the index date.

Results

A total of 8,454 patients had an index claim for etanercept (n = 4,224), adalimumab (n = 2,941), or infliximab (n = 1,289). Treatment patterns in the first year across all four conditions combined for etanercept, adalimumab, or infliximab, respectively, were: persistence, 42%, 47%, and 56%; restarting, 25%, 19%, and 12%; switching, 13%, 12%, and 13%; and stopping, 20%, 22%, and 19%. The combined rates of either persistence or restarting initial therapy after a treatment gap were 67%, 66%, and 68%, for etanercept, adalimumab, and infliximab, respectively. Most switches (66?C92%) were between the three TNF blockers.

Conclusion

In the first year after initiating TNF blocker therapy, patients often have a ??45-day treatment gap; however, approximately two-thirds of patients are either persistent with or restart their index therapy in the year following TNF blocker initiation.     

Estimating Effectiveness and Cost of Biologics for Rheumatoid Arthritis: Application of a Validated Algorithm to Commercial Insurance Claims

Purpose

The aim of this analysis was to implement a claims-based algorithm to estimate biologic cost per effectively treated patient for biologics approved for moderate to severe rheumatoid arthritis (RA).

Methods

This retrospective analysis included commercially insured adults (aged 18–63 years) with RA in a commercial database, who initiated biologic treatment with abatacept, adalimumab, etanercept, golimumab, or infliximab between 2007 and 2010. The algorithm defined effectiveness as having all of the following: high adherence, no biologic dose increase, no biologic switching, no new nonbiologic disease-modifying antirheumatic drug, no increased or new oral glucocorticoid use, and no more than 1 glucocorticoid injection. For each biologic, cost per effectively treated patient was defined as total drug and administration costs (from allowed amounts on claims), divided by the number of patients categorized as effectively treated.

Findings

Of 15,351 patients, 12,018 (78.3%) were women, and the mean (SD) age was 49.7 (9.6) years. The algorithm categorized treatment as effective in the first year for 30% (1899/6374) of etanercept, 30% (1396/4661) of adalimumab, 20% (560/2765) of infliximab, 27% (361/1338) of abatacept, and 29% (62/213) of golimumab treated patients. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was lowest for etanercept ($49,952), followed by golimumab ($50,189), adalimumab ($52,858), abatacept ($71,866), and infliximab ($104,333).

Implications

Algorithm-defined effectiveness was similar for biologics other than infliximab. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics.     

Vedolizumab and etrolizumab for ulcerative colitis: twins or simple cousins?

ABSTRACT

Introduction: Vedolizumab is a monoclonal antibody that selectively blocks α4β7 integrin and has already been approved for use in patients with moderate-to-severe ulcerative colitis both as first and second line. Etrolizumab is a monoclonal antibody still being tested, which acts with a dual mechanism by selectively inhibiting both α4β7 and αEβ7 integrins.

Areas covered: This review provides an overview of the literature data of vedolizumab and etrolizumab, in order to define their role in the treatment of patients with moderate-to-severe ulcerative colitis.

Expert opinion: Etrolizumab and vedolizumab block the α4β7 integrin with a similar action mechanism. However, the inhibition of αEβ7 integrin by etrolizumab distinguishes the two anti-integrins making them ‘cousin’ drugs. Phase 3 clinical trials are needed to confirm the promising etrolizumab’s efficacy data and to resolve any doubts about its safety, allowing a clearer comparison with vedolizumab.     

Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor-α antagonists

Background: Rheumatoid arthritis (RA) is a disabling autoimmune disease; unless adequately controlled, patients have a poor long-term prognosis. Tumour necrosis factor (TNF)-α antagonists have provided relief for many RA patients; however, despite their efficacy, some patients do not respond or fail to maintain initial response. In the UK, patients with an inadequate response to TNF-α antagonists have limited options, as the National Institute of Clinical Excellence (NICE) currently only recommend switching to an alternative TNF-α antagonists if discontinuation occurs due to safety during the first 6 months of treatment. The EU has approved three biological agents, rituximab, abatacept, and tocilizumab, for patients with RA with an inadequate response to TNF-α antagonists. Objective: This review examines the clinical experience with two therapies targeting key immune cells involved in RA – rituximab (lyses B-cells), and abatacept (T-cell co-stimulation modulator) – specifically focusing on patients with an inadequate response to TNF-α blockade. Methods: Phase II/III clinical trials and original studies were identified using Medline and Pubmed; articles assessing the efficacy and/or safety of rituximab or abatacept in patients with RA refractory to TNF-α blockade were reviewed. Conclusions: Clinical data for rituximab and abatacept demonstrate that both reduce disease activity in TNF-α antagonist inadequate responders, suggesting that agents with alternative mechanisms of action, such as those targeting key immune cells, may be useful in this patient population.     

Efficacy and Safety of Vedolizumab in Ulcerative Colitis and Crohn’s Disease Patients Stratified by Age

Introduction

The efficacy and safety of vedolizumab, a gut-selective α₄β₇ integrin antibody, were demonstrated in the GEMINI 1 and GEMINI 2 clinical trials of adults aged 18–80 years. We investigated the efficacy and safety of vedolizumab in patients stratified by age from the GEMINI trials.

Methods

Safety and efficacy, including clinical response, clinical remission, and corticosteroid-free remission, at week 6 and/or 52 were determined post hoc in patients aged <35, 35 to <55, and ≥55 years.

Results

At baseline, 353, 412, and 130 ulcerative colitis (UC) and 582, 443, and 90 Crohn’s disease (CD) patients were aged <35, 35 to <55, and ≥55. Of these patients, 56 were aged ≥65 years (UC: 33, CD: 23). Trends favoring vedolizumab over placebo were observed for most efficacy endpoints irrespective of patient age; some variability between subgroups was observed. Safety profiles of vedolizumab and placebo were similar in all age groups. Vedolizumab-treated patients aged ≥55 had the lowest incidence of serious infections (0.9 per 100 person–years) and adverse events leading to hospitalization (14.8 per 100 person–years). There were no age-related differences in the incidence of adverse hematological events, malignancy, or death.

Conclusions

The safety and efficacy of vedolizumab in patients with UC or CD were similar for all age groups. The number of patients in the oldest age group in these analyses was small; thus further studies of vedolizumab in larger cohorts of elderly patients are warranted.

Funding

Millennium Pharmaceuticals, Inc. (d/b/a Takeda Pharmaceuticals International Co.).

     

Update on biologicals for treatment of juvenile idiopathic arthritis

Introduction: The development of biologics has markedly changed the treatment of JIA. Complete control of the disease and remission has today become the main goal of treatment preventing long-term damage and disability.

Areas covered: This review gives an overview of the current treatment options using biologics in JIA. The biologic drugs are discussed on the basis of recent clinical trials.

Expert opinion: While JIA is a group of heterogeneous diseases, differences in their biology turned out to influence treatment success with different biologics. TNF inhibitors emerged to be the most commonly used biologics for the treatment of JIA. First they were successful for the treatment of rheumatoid factor positive and negative polyarticular JIA. TNF inhibitors have also been studied in patients with enthesitis-related arthritis, psoriatic arthritis, and extended olioarthritis, and approval of at least etanercept is expected. Second-line biologics are abatacept and tocilizumab. For systemic onset JIA, tocilizumab, and the IL-1 inhibitors anakinra and canakinumab have been successfully studied. In the treatment of JIA, biologics have emerged as potent drugs to control the disease. New advancements will be crucial for further improvement of treatment options in JIA.     

Utilization and Adherence Patterns of Subcutaneously Administered Anti–Tumor Necrosis Factor Treatment Among Rheumatoid Arthritis Patients

Background

Adherence to therapy is a key requirement underlying achievement of clinical outcomes in randomized controlled drug registration trials. In postmarketing studies, comparison of adherence among therapies can become more complicated when drug dosing and administration schedules differ or when methods used to measure adherence are not consistently applied.

Objective

The objective of this exploratory study was to investigate a broad range of utilization and adherence outcomes associated with subcutaneous biologic treatments for rheumatoid arthritis (RA).

Methods

Adult patients (aged ≥18 years) exhibiting ≥2 claims with an RA diagnosis (code 714.x), at least 24 months of continuous medical and pharmacy eligibility, and 30-day supplies of adalimumab, etanercept, or golimumab were selected from the Optum Insight Clinformatics database. Adherence and utilization measures were calculated and compared across treatment groups.

Results

A total of 1532 adalimumab, 2099 etanercept, and 261 golimumab patients met inclusion criteria. Compared with both adalimumab and etanercept patients, golimumab patients were significantly more likely to have a medication possession ratio of ≥0.80 (82% vs 71% vs 62%; P < 0.001) and significantly less likely to have ≥4 late medication refills (6.9% vs 17.7% vs 26.1%; P < 0.001 for all). Etanercept patients had significantly greater refill intervals (37.7 vs 34.9 and 35.1 days) and had the lowest proportion of adherent fills (70% vs 77% and 75%) compared with both golimumab and adalimumab patients (P < 0.001 for all). Bivariate effects were reproduced in multivariate models that controlled for treatment duration.

Conclusions

A number of statistically significant medication adherence differences were observed among golimumab, adalimumab, and etanercept patients in treatment for RA. Overall, golimumab patients appeared to be the most adherent group. Findings may be partially attributable to golimumab patients’ likely increased disease severity, their prior experience with biologic medication, or golimumab’s once-monthly dosing schedule, which requires fewer administrations than both adalimumab and etanercept.     

Golimumab for the treatment of axial spondyloarthritis

Introduction: Anti-TNF drugs have represented an epochal revolution in the treatment of rheumatoid arthritis and spondyloarthritis. In the field of axial spondyloarthritis, golimumab, a fully human monoclonal anti-TNFα administered subcutaneously every 4 weeks, has shown significant efficacy and good safety in patients with ankylosing spondylitis. More recently, it was also indicated as an effective treatment for patients suffering from non-radiographic axial spondyloarthitits.

Areas covered: A systematic literature search was completed, using the largest electronic databases (Medline, Embase and Cochrane), with the aim to review all data concerning the administration of golimumab in patients suffering from axial spondyloartritis.

Expert opinion: In the 16-week GO-AHEAD study, golimumab was effective in patients with non-radiographic spondyloarthritis with high levels of CRP and/or positive MRI findings, but not in subjects with both negative CRP and MRI. This finding allows for the addressing the of anti-TNF treatment more specifically. Preliminary data concerning an open-label extension of the GO-AHEAD study outlined the high retention-rate of the drug at 52 weeks. The production of antibodies against golimumab is rare and it seems to exert scarce influence on the drug performances. In conclusion, golimumab appears as a very useful and well tolerated anti-TNF agent.     

Abatacept: a biologic immune modulator for rheumatoid arthritis

Introduction: Abatacept is a biologic drug that belongs to the class of T-cell co-stimulation modulators and is used for the treatment of rheumatoid arthritis (RA).

Areas covered: This article covers major randomized clinical trials and meta-analyses concerning abatacept in the treatment of RA, as identified in a Pubmed search. Scientific meeting abstracts describing long-term extension data of the identified trials are also included. Efficacy outcomes and the safety profile are the focus of this evaluation.

Expert opinion: Abatacept in combination with methotrexate (MTX) or other synthetic disease-modifying anti-rheumatic drugs (DMARD) has been proven effective for the treatment of RA in different groups of patients: with early RA and no prior exposure to DMARD; with DMARD-resistant RA; and with RA not responding to TNF-α-blocking agents. Significant reductions of disease activity are achieved, with 1-year remission rates reaching up to 41% of DMARD-naïve patients with early RA receiving a combination of abatacept plus MTX. Abatacept treatment has been shown to improve function and quality of life and to suppress radiographic progression. No major safety issues have emerged during clinical trials and long-term extensions. Therefore, abatacept is a drug with a favorable efficacy and safety profile, which may offer substantial benefits to RA patients.     

Low immunogenicity of vedolizumab determined by a simple drug-tolerant assay in patients with ulcerative colitis

Vedolizumab is a humanized monoclonal antibody against the α4β7 integrin and is approved for treatment of inflammatory bowel diseases. In this study, we evaluated the immunogenicity of vedolizumab using a simple drug-tolerant assay developed in our laboratory. Serum vedolizumab trough levels and anti-vedolizumab antibody (AVA) levels were measured using new immunoassays in 37 patients with ulcerative colitis (UC) under vedolizumab maintenance therapy. The median vedolizumab trough level at week 30 was 16.0 μg/ml (interquartile range, 7.3–24.4). The vedolizumab trough level of the patients with clinical remission (partial Mayo score ≤1) was significantly higher than that of clinically active patients (16.7 μg/ml vs 6.8). The cut-off value of vedolizumab level predicting clinical remission at week 30 was 7.34 μg/ml. The median AVA level of patients under vedolizumab maintenance therapy was similar to that of healthy controls (n = 20) (0.032 μg/ml-c vs 0.022). One of 37 patients (2.7%) was judged to be AVA positive. There was no significant difference in serum AVA and vedolizumab trough levels between biologics-naïve (n = 19) and biologics-switched (prior anti-TNFα-exposed) patients (n = 18). In conclusion, the simple drug-tolerant assay developed in our laboratory demonstrated low immuno­genicity of vedolizumab. Prior use of anti-TNFα drugs did not affect the immunogenicity of vedolizumab.     

Persistence Among Patients with Crohn Disease Previously Treated with an Anti-tumor Necrosis Factor Inhibitor and Switching or Cycling to Another Biologic Agent

PurposeNonresponse to an anti–tumor necrosis factor (TNF) agent in patients with Crohn disease (CD) is often managed by either a switch to a different class of biologic (ie, ustekinumab, vedolizumab) or by cycling to another anti-TNF agent (ie, adalimumab, infliximab, certolizumab pegol). Persistence after a switch to a different biologic class or after cycling within the anti-TNF class was assessed in patients with nonresponse to an anti-TNF agent.MethodsAdults with CD who discontinued from an anti-TNF agent and either switched to a different class of biologic (ie, anti-interleukin/integrin; the switching cohort) or cycled within the anti-TNF class (the cycling cohort) between September 23, 2016, and August 1, 2019, were selected from a commercial database. The index date was defined as the date of the first claim of the subsequent-line biologic (index biologic) after an anti-TNF. The switching and cycling cohorts were balanced with regard to baseline characteristics, using inverse probability of treatment weights–average treatment effect (IPTW-ATE). Persistence with the index biologic was defined as consistent use with no gaps of >120 days (ustekinumab, vedolizumab, infliximab) or of >60 days (adalimumab, certolizumab pegol) in biologic supply. Composite end points were persistence while being corticosteroid-free (defined as no use of corticosteroids with ≥14 days of supply after day 90 post-index) and persistence while on monotherapy (no immunomodulators/nonindex biologics). Weighted Kaplan-Meier and Cox models were used to assess outcomes at 12 months post-index.FindingsThere were 444 patients in the weighted switching cohort (mean age, 40.4 years; 56.3% female) and 441 in the weighted cycling cohort (mean age, 39.5 years; 58.4% female). At 12 months post-index, the rate of persistence with the index biologic was 75.7% in the switching cohort compared to 67.5% in the cycling cohort (log-rank P = 0.023); the rate of persistence while on monotherapy was 58.2% compared to 44.2%, respectively (log-rank P < 0.001). The rate of persistence was 44% greater in the switching compared to that in the cycling cohort (hazard ratio [HR] = 1.44; 95% CI, 1.11–1.88; P = 0.007); the rate of persistence while on monotherapy was 56% greater in the switching cohort (HR = 1.56; 95% CI, 1.28–1.90; P < 0.001). The between-cohort difference in persistence while being corticosteroid-free was not statistically significant (HR = 1.08; 95% CI, 0.89–1.32; P = 0.426).ImplicationsPatients with CD who switched to a different biologic class were more persistent than were patients who cycled to another anti-TNF agent. These findings may be useful for physicians when considering the treatment of patients who have experienced nonresponse or loss of response to the first-line anti-TNF agent.