Frequency of biologic switching and the outcomes of switching in children and young people with juvenile idiopathic arthritis: a national cohort study

Abstract

Background Information is scarce about biological disease-modifying antirheumatic drug (DMARD) switching patterns in children and young people (aged ≤16 years) with juvenile idiopathic arthritis in an era of many biologic therapies. The best choice of biologic to use if the first biological DMARD is not beneficial also remains unclear. We aimed to quantify and characterise biologic switching patterns in children and young people with juvenile idiopathic arthritis, and to compare the effectiveness of using a second tumour necrosis factor inhibitor (TNFi) versus non-TNF is following failure of a first TNFi biologic in routine clinical practice. Methods Our study population comprised patients with juvenile idiopathic arthritis who were enrolled in two parallel UK cohort studies (the British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study [BSPAR-ETN] and the Biologics for Children with Rheumatic Diseases [BCRD] study) between Jan 1, 2004, and April 11, 2019. Data on disease characteristics and DMARD therapy were collected at the time of initiation of a first biologic, at 6 months, at 1 year, and annually thereafter. Biologic switching patterns were described in all patients who started their first biologic from Jan 1, 2010, onwards. Among patients who started treatment with their first biologic from Jan 1, 2004, onwards, had polyarticular course juvenile idiopathic arthritis (extended oligoarthritis or polyarthritis [positive or negative for rheumatoid factor]), and who had started a second biologic, we assessed changes in outcome variables at 6 months compared with baseline and compared the proportion of patients who achieved an American College of Rheumatology Pediatric (ACR Pedi) 90 response and minimal disease activity at 6 months on the basis of the class of the second biologic (a second TNFi vs non-TNFi biologic). Changes in outcome variables at 6 months were compared using linear regression or logistic regression, adjusted for propensity quintiles to account for confounding by indication. We used multiple imputation to account for missing data.

Persistence and Adherence to Biologic Therapies in Juvenile Idiopathic Arthritis

“…Around 50% of our patients needed a biologic therapy to control disease activity, and 16% and 7.6% needed a second and third biologic respectively. Our results are similar to other international studies in which the authors also followed this T2T strategy 6,8 . However, the clinical response in our cohort was slightly better with a complete remission after 6 months obtained in more than three thirds of the patients, increasing to more than 80% at 12 months.…”

“…Polyarticular JIA requires bDMARD in around 50% of cases to accomplish the treatment goal 6 , which is remission 7,8 . However, more important than the systemic treatment is to follow a treat-to-target approach that has proven to improve disease activity no matter what systemic drugs are used [8][9][10] .…”

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis

“…TNF-α inhibitors, such as etanercept (human dimeric fusion protein which functions as a decoy receptor and binds to soluble TNF-α), adalimumab (human monoclonal antibody -mAb- which binds with high affinity both soluble and membrane-bound TNF-α) and infliximab (chimeric mAb which blocks both soluble and trans-membrane TNF-α) are widely used in JIA. In fact, etanercept is one of the most frequently prescribed biologics for JIA in many countries, including the United Kingdom ( Geikowski et al, 2014 ; Kearsley-Fleet et al, 2020 ). Other biologics include tocilizumab (humanized mAb which blocks both soluble and trans-membrane IL-6), anakinra (human IL-1 receptor agonist which blocks IL-1 type 1 receptor) and canakinumab (human mAb against IL-1β), abatacept (human cytotoxic T-lymphocyte-associated protein 4 immunoglobulin fusion protein, acting as T-cell co-stimulatory blockade) and rituximab, a chimeric anti-CD20 mAb causing B-cell depletion.…”

“…Despite the positive short-term outcomes in numerous studies ( Ungar et al, 2013 ), many patients switch biologics due to primary inefficacy, loss of response or adverse effects. Data from biologic registries in the United Kingdom, suggest that 23% of patients receive at least two biologic drugs, 5% at least three and 1% four or more biologic drugs within a median observational period of 2.2 years ( Kearsley-Fleet et al, 2020 ). The retention rate of biologics declines with time, from 92.9% in the first year of treatment to 68.1% at 4 years, according to a Portuguese registry ( Mourao et al, 2016 ).…”

Increased Risk of Temporomandibular Joint Disorder in Patients with Rheumatoid Arthritis: A Longitudinal Follow-Up Study

“…Rheumatoid arthritis (RA) is an autoimmune disease that occurs not only in the elderly, but also in younger patients [1]. RA is one of the most prevalent chronic inflammatory diseases [2].…”