csDMARD Monotherapy Research Articles

Trends in New Use of Disease-Modifying Antirheumatic Drugs in Juvenile Idiopathic Arthritis Among Commercially Insured Children in the United States from 2001-2022.

To describe recent trends in DMARD use for children with juvenile idiopathic arthritis (JIA) in the US. We used commercial claims data (2000-2022) to perform a serial cross-sectional utilization study of children ages 1-18 diagnosed with JIA. Initiations of conventional synthetic (cs), biologic (b), or targeted synthetic (ts) DMARDs were identified after a ≥12-month baseline and expressed as percentage of all new DMARD initiations per year, by category, class, and individual agent. Trends were evaluated using linear regression. Secondarily, we examined first b/tsDMARDs initiated after csDMARD monotherapy. We identified 20,258 new DMARD use episodes among 13,696 individuals (median age 14 years, 67.5% female). csDMARDs, while most commonly used overall, declined from 89.5% of new use episodes to 43.2% (2001-2022, p<0.001 for trend). In contrast, bDMARD use increased (10.5-50.0%, p<0.001). For tumor necrosis factor inhibitors (TNFi), etanercept peaked at 28.3% (2006) and declined to 4.2% (2022) (p=0.002). Meanwhile, adalimumab use doubled (7.0-14.0%, 2007-2008) after JIA approval, increasing further following a less painful formulation release (20.5%, 2022, p<0.001). However, overall TNFi use has declined with increasing use of other b/tsDMARDs, particularly ustekinumab, secukinumab, and tofacitinib. By 2022, adalimumab was the most common b/tsDMARD initiated first after csDMARDs (77.8%). Among commercially insured children with JIA in the US, new b/tsDMARD use is rising while new csDMARD use declines. For b/tsDMARDs, adalimumab is most used and the predominant b/tsDMARD initiated first after csDMARDs. Patterns in DMARD use for JIA have evolved relative to multiple factors, including regulatory approvals and tolerability.

Risk of incident cardiovascular events with disease-modifying anti-rheumatic drugs among adults with rheumatoid arthritis: a nested case-control study.

This study examined the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). This nested case-control study used the MarketScan database (2012-2014), involving adult RA patients (aged ≥18 years) initiating either a conventional synthetic (cs) DMARD, biologic DMARD, or targeted synthetic (ts) DMARD between January 1, 2013 and December 31, 2014 (cohort entry) and had no CVD history. Cases were individuals with incident CVD identified using diagnosis codes or procedure codes from medical claims. For each case, 10 age- and sex-matched controls were selected using the incident density sampling with replacement. Prescriptions of DMARDs were measured 90 days before the event date. Conditional logistic regression examined the association of risk of CVD with DMARDs in combination treatment or individual use, with reference to methotrexate (MTX) monotherapy, adjusting for baseline confounders. Subgroup analyses were performed separately in DMARD combination therapy users or individual DMARD users, respectively. In total, 270 cases of incident CVD and 2700 controls were included (mean [standard deviation (SD)] age: 54[1]; 75.6% women). The commonly prescribed DMARD therapies were csDMARD monotherapy (n = 795, 27.04%), followed by tumor necrosis factor inhibitors (TNFi) monotherapy (n = 367, 12.48%), and TNFi in combination with MTX (n = 314, 10.68%). Compared with MTX monotherapy, overall use of DMARD agents was not associated with the differential risk of CVD, including various types of DMARD combination regimens. The findings were similar across subgroup analyses. The study found no differential risk of CVD with DMARDs in combination therapy or monotherapy compared to MTX monotherapy in patients with RA. Key Points • This study evaluated the risk of cardiovascular disease (CVD) associated with the disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA). • Findings suggest no differential CVD risk with DMARDs in combination with MTX or used individually compared with MTX monotherapy in patients with early RA. • Further efforts should focus on a better understanding of the mechanism of DMARD combination treatments with MTX in modifying CV risk.

Predictors of low spike antibody response in patients with systemic rheumatic disease after an initial course of COVID-19 vaccination.

Patients with rheumatic disease may mount a suboptimal serologic response to COVID-19 vaccination. We evaluated predictors of low antibody response in a clinic-based cohort. We conducted a cross-sectional study using electronic health record (EHR) data at Brigham and Women's Hospital, Boston, MA. Patients with systemic rheumatic disease that had SARS-CoV-2 spike antibody (Ab) tested using the Roche Elecsys immunoassay, February-August 2021, after 2 doses of mRNA vaccine or 1 dose of adenovirus vector vaccine were identified. Demographics, systemic rheumatic disease, vaccination dates, and disease-modifying antirheumatic drugs (DMARDs) were extracted. The primary outcome was low spike Ab (≤ 200 U/mL). Logistic regression models estimated predictors of low spike Ab. Among 382 patients, the mean age was 57 years, 77% were female, and 37% had low spike Ab. Older age (OR 1.03, 95% CI [1.02, 1.05]), SLE (OR 4.81 [2.08, 8.43], reference: inflammatory arthritis), prednisone (OR 1.67 [1.03, 2.74]), and rituximab (OR 22.91 [9.85, 53.29]) were significantly associated with higher odds of low spike Ab. Use of csDMARD monotherapy (OR 0.12 [0.04, 0.33]) and JAK inhibitors (OR 0.41 [0.18, 0.92]) were associated with significantly lower odds for low spike Ab. After adjusting for systemic rheumatic disease and DMARDs, SLE and rituximab remained significantly associated with low spike Ab. Over a third of patients with systemic rheumatic disease with spike Ab tested in routine care had low spike Ab after 2 doses of mRNA or 1 dose of adenovirus vector COVID-19 vaccine. SLE and rituximab were significant risk factors for low spike Ab. • More than one-third of patients with systemic rheumatic disease that had spike Ab tested in routine care had low spike Ab after 2 doses of mRNA or 1 dose of adenovirus vector COVID-19 vaccine. • Diagnosis of SLE, use of prednisone, and use of rituximab were significantly associated with greater odds of low spike antibodies. • These data underscore the importance of additional doses of COVID-19 vaccine and prophylactic Evusheld in immunosuppressed patients with systemic rheumatic disease as recommended by the US Centers for Disease Control.

Upadacitinib for the Treatment of Rheumatoid Arthritis: An Extensive Review.

To review the characteristics, efficacy, safety, pharmacoeconomics, and place in therapy of upadacitinib, a Janus kinase (JAK) inhibitor, in the treatment of rheumatoid arthritis (RA). PubMed (January 2003-May 2022) was searched using upadacitinib and ABT-494. Human studies published in peer-reviewed publications in English were the primary sources for efficacy and safety data. In randomized, double-blind, controlled clinical studies, upadacitinib demonstrated statistically significant improvement in RA symptoms as monotherapy and in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) when compared with csDMARD monotherapy or to adalimumab or abatacept in combination with csDMARD therapy in patients with RA. American College of Rheumatology 20% response rates were 68% to 79% for upadacitinib monotherapy and 64% to 84% for upadacitinib plus csDMARD therapy, compared with 28% to 59% for csDMARD-only therapy and 63% to 74% for biologic DMARD (bDMARD) plus csDMARD therapy. Long-term extension studies demonstrated similar findings. Upadacitinib had similar rates of serious infections, herpes zoster, major cardiovascular events, and venous thromboembolic events as other JAK inhibitors. Upadacitinib was similar in cost to tofacitinib and twice as high as baricitinib based on current estimated costs to patients, but actual costs may vary. Upadacitinib is an alternative therapy to other JAK inhibitors and bDMARDs in patients with moderate to severe RA who have had an inadequate response to a tumor necrosis factor inhibitor alone or in combination with a csDMARD. Upadacitinib is an effective JAK inhibitor for use in RA.

Harmonization of Public Coverage Policies for Biologic Drugs in the Treatment of Rheumatoid Arthritis

&#x0D; For rheumatoid arthritis (RA), treatment guidelines and clinical evidence support the combination (either dual or triple) of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) before accessing a biologic DMARD (bDMARD). Federal, provincial, and territorial (FPT) drug plans currently have different coverage criteria for bDMARD eligibility in RA. To align their criteria, these plans should consider the inclusion of at least 1 line of combination csDMARDs before a bDMARD:&#x0D; &#x0D; For dual csDMARDs: Saskatchewan, Veterans Affairs Canada, and Canadian Armed Forces would need to change their current coverage criteria to include at least 1 line of dual csDMARDs before access to a bDMARD.&#x0D; For triple csDMARDs: Alberta, Saskatchewan, Manitoba, Veterans Affairs Canada, and Canadian Armed Forces would need to alter their current coverage criteria because each of these FPT drug plans only consider csDMARD monotherapy or dual csDMARDs in their current coverage criteria.&#x0D; &#x0D; &#x0D; Most FPT drug plans require a failure of at least 2 lines to 3 lines of csDMARD therapy before a bDMARD, except British Columbia, Ontario, Newfoundland and Labrador, Veterans Affairs Canada, and Canadian Armed Forces, which offer an option to access bDMARDs after 1 line of combination csDMARDs. British Columbia, Ontario, the Atlantic provinces, Yukon, Correctional Service of Canada, and Non-Insured Health Benefits include triple csDMARDs in their coverage criteria. Alberta, Manitoba, Veterans Affairs Canada, and Canadian Armed Forces include dual, but not triple, csDMARDs in their criteria; however, Veterans Affairs Canada and Canadian Armed Forces do not require a trial of dual csDMARDs if 2 lines of csDMARD monotherapy have been attempted. Saskatchewan is the only jurisdiction that only requires csDMARD monotherapy. Canadian private insurers have also reached a consensus to implement a trial requirement of dual csDMARDs before a bDMARD across their formularies.&#x0D; Evidence-based guidelines, including the 2012 Canadian Rheumatology Association guidelines, recommend csDMARD monotherapy (methotrexate [MTX] is preferred unless contraindicated) as first-line treatment for RA, although a guideline published in 2018 by the Brazilian Society of Rheumatology stated that combination therapy with 2 or more csDMARDs may also be used as a first-line treatment. These guidelines generally recommend combination csDMARDs after csDMARD monotherapy is deemed ineffective.&#x0D; A network meta-analysis found that triple csDMARDs is more efficacious than dual csDMARDs, etanercept monotherapy, and 4 mg/kg tocilizumab monotherapy and comparable to other bDMARDs (alone or in combination with MTX), targeted synthetic DMARDs in combination with MTX, and biosimilars in combination with MTX. Additionally, economic evidence demonstrated that triple csDMARDs is more cost-effective than etanercept plus MTX combination therapy.&#x0D; Time to first bDMARD was, on average, longer in Alberta, British Columbia, and Ontario than in Saskatchewan, Manitoba, and the Atlantic provinces by approximately 4 months, which may be partially explained by differences in coverage criteria for the number of prior lines of csDMARD therapy required. Increasing the time to initiating a bDMARD could lead to budget savings without impacting clinical outcomes.&#x0D;

Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis

ObjectivesA considerable proportion of patients with rheumatoid arthritis (RA) also suffer from hand osteoarthritis (OA). We here assess the association between conventional synthetic (cs) and biological (b) disease-modifying antirheumatic drugs (DMARDs) and radiographic distal interphalangeal-(DIP) OA in patients with RA.MethodsAdult RA patients from a longitudinal Swiss registry of rheumatic diseases who had ≥ 2 hand radiographs were included at the first radiograph and followed until the outcome or the last radiograph. Patients were grouped into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for the severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. KLS ≥ 2 in ≥ 1 DIP joint indicated incident or existing OA, and increase of ≥ 1 in KLS in ≥ 1 DIP joint indicated progression in existing DIP OA. Time-varying Cox regression and generalized estimating equation (GEE) analyses were performed. We estimated hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) of DIP OA incidence (cohort 2), or progression (cohort 1), in bDMARD monotherapy, bDMARD/csDMARD combination therapy, and past or never DMARD use, when compared to csDMARD use. In post hoc analyses, we descriptively and analytically assessed the individual KLS features in cohort 1.ResultsAmong 2234 RA patients with 5928 radiographs, 1340 patients had DIP OA at baseline (cohort 1). Radiographic progression of DIP OA was characterized by new or progressive osteophyte formation (666, 52.4%), joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), or erosions (62, 4.3%). bDMARD monotherapy had an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34 [95% CI 1.07–1.69]). The risk was not significant in csDMARD/bDMARD combination users (HR 1.12 [95% CI 0.96–1.31]), absent in past DMARD users (HR 0.96 [95% CI 0.66–1.41]), and significantly lower among never DMARD users (HR 0.54 [95% CI 0.33–0.90]). Osteophyte progression (HR 1.74 [95% CI 1.11–2.74]) was the most significantly increased OA feature with bDMARD use compared to csDMARD use. In 894 patients without initial DIP OA (cohort 2), the risk of incident OA did not differ between the treatment groups. The results from GEE analyses corroborated all findings.ConclusionsThese real-world RA cohort data indicate that monotherapy with bDMARDs is associated with increased radiographic progression of existing DIP OA, but not with incident DIP OA.

Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry

BackgroundUnderstanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry.MethodsThis was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004–2007, 2008–2011, and 2012–2015.ResultsThis study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004–2007 period; 38.6% and 38.2%, respectively, in the 2008–2011 period; and 35.2% for both in the 2012–2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012–2015 vs 2004–2007 and 2008–2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry.ConclusionsIncreased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012–2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.

PSY14 Disparities in Targeted Immune Modulating (TIM) Treatment for Elderly Compared to Younger Patients with Psoriatic Arthritis (PSA); Observations of US Clinical Practice from Trio Health and the American Rheumatology Network (ARN)

Targeted immunomodulating (TIM) therapies (JAK inhibitors and biologics) are as effective in the elderly as in younger patients with PsA. However, balancing the greater comorbidity burden associated with aging may influence prescribing patterns as clinicians seek to avoid serious adverse events in the ≥65-year-old population. Here, we examine associations between age and TIM treatment patterns in a large US community rheumatology practice registry. This study analyzed patients diagnosed with PsA and who initiated care with conventional synthetic DMARD (csDMARD) monotherapy between Jan 2014 to Nov 2019 with follow-up of ≥6 months. Disease Activity Scores (DAS) were calculated using CDAI or RAPID-3. Differences in time to initiation of TIM containing regimens were analyzed with KM curves and associated Log-Rank Test for difference in hazard. 524 patients met all inclusion criteria. Age groups <65y (387, 74%) and ≥65y (137, 26%) were not significantly different by gender, race, ethnicity, hypertension, or baseline DAS. Diabetes and osteoporosis were significantly higher in the ≥65y group (p<0.01). 495 (94%) of patients initiated TIM therapy within 2 years of first csDMARD regimen. No differences in time to initiation of TIM were observed by baseline DAS (p = 0.11) or payer type (p = 0.29). Via KM Curves, patients in the older cohort remained on csDMARD regimens significantly longer than younger patients, 6.8 vs. 4.0 months [p=0.02] . Upon treatment with TIM therapies, patients ≥65y were more likely to receive infused therapy +/- csDMARDS (22% ≥65y vs 12% <65y, p<0.01). Overall, comorbidity burden is an important consideration in timing and choice of targeted therapies. These data suggest that differences in treatment exist between age groups even when comorbidity differences are minimized and raise the possibility to age bias may influence care for ≥65y population.

First-line csDMARD monotherapy drug retention in psoriatic arthritis: methotrexate outperforms sulfasalazine

ObjectivesConventional synthetic DMARDs (csDMARDs) are the first-line treatment for PsA, but there is conflicting data regarding their efficacy and scarce reports describing the duration of use (drug retention) of csDMARD in this population. Their position in treatment recommendations is a matter of growing debate due to the availability of alternative treatment options with higher levels of evidence. We aimed to study drug retention and predictors for drug retention among PsA patients receiving first-line csDMARD monotherapy.MethodsRetrospective cohort study in DMARD-naïve adult PsA patients in whom a first csDMARD was prescribed as monotherapy primarily to treat PsA-related symptoms. The main outcome was time to failure of the csDMARD (i.e. stopping the csDMARD or adding another DMARD).ResultsA total of 187 patients were included, who were mainly prescribed MTX (n = 163) or SSZ (n = 21). The pooled median drug retention time was 31.8 months (interquartile range 9.04–110). Drug retention was significantly higher in MTX (median 34.5 months; interquartile range 9.60–123) as compared with SSZ-treated patients (median 12.0 months; interquartile range 4.80– 55.7) (P =0.016, log-rank test). In multivariable Cox regression, the use of MTX and older age were associated with increased retention. The main reasons for treatment failure were inefficacy (52%) and side effects (28%). Upon failure, MTX treated patients were more commonly, subsequently treated with a biologic DMARD compared with SSZ (P < 0.05).ConclusionMTX outperforms SSZ as a first-line csDMARD in DMARD-naïve PsA patients with respect to monotherapy drug retention in daily clinical practice.

Clinical characteristics, disease activity, functional status, and quality of life results of patients with psoriatic arthritis using biological and conventional synthetic disease-modifying antirheumatic drugs.

Objectives This study aims to compare the clinical characteristics, disease activity, and quality of life (QoL) of patients with psoriatic arthritis (PsA) who use biological and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in a nationwide cohort throughout Turkey.Patients and methods A total of 961 patients (346 males, 615 females; mean age 46.9±12.2 years; range, 18 to 81 years) with PsA according to the classification criteria for PsA were included in the study. The patients’ demographic and clinical characteristics, physical examination results, Disease Activity Score 28, Disease Activity Index for Psoriatic Arthritis and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Psoriasis Area and Severity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Hospital Anxiety and Depression Scale, Health Assessment Questionnaire, Psoriatic Arthritis Quality of Life (PsAQoL), and short form-36 scores were all recorded.Results Of the patients, 23% underwent biological DMARD (bDMARD) monotherapy, 42% underwent conventional synthetic DMARD (csDMARD) monotherapy, 10% underwent a csDMARD combination therapy, and 10% underwent a combination bDMARD and csDMARD treatment. The visual analog scale (VAS pain), patient global assessment, physician global assessment, and BASDAI scores were found to be lower among patients using combination treatment of csDMARD and bDMARD, while the swollen joint count was found to be lower among patients using bDMARD. The PsAQoL score was found to be the lowest among patients not using any medication and the highest among those using bDMARD.ConclusionIn our study, patients with PsA were successfully treated with both csDMARD and bDMARD monotherapy. When the biological treatments used for PsA were compared with csDMARD, it was found that biological treatments had a positive effect on both disease activity and the QoL. Combinations of csDMARDs and bDMARDs were preferred in cases in which the disease activity was still high or increased. Because of the highest efficacy of the combined treatment, we highly suggest increasing the number of patients on combined treatment.

Therapeutic Options and Cost-Effectiveness for Rheumatoid Arthritis Treatment.

During the last two decades, the therapeutic decisions and strategies for rheumatoid arthritis (RA) management have improved dramatically. Today, the therapeutic armamentarium is significantly augmented, and by using both old and new drugs, remission or low disease activity is a reasonable goal. The use of conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) in combination with biologic (b) or targeted synthetic (ts) DMARDs has revolutionized RA treatment. Methotrexate administration is considered fundamental among other csDMARDs for the treatment of RA. It is recommended as the initial drug (monotherapy), or in combination with other csDMARDs, bDMARDs, and tsDMARDs in a step-up strategy. Furthermore, it can be used with other csDMARDs as initial combination-therapy. On the other hand, despite the fact that bDMARDs and ts DMARDs are highly efficacious and can also be used as monotherapy in certain cases, cost-effectiveness is still questionable when compared with csDMARDs. In this direction, the classic argument of utmost importance has to do with the most appropriate treatment strategy that shall be initially applied: csDMARD combination-therapy versus monotherapy, or step-up combinationtherapy with bDMARDs, especially tumor necrosis factor-α (TNFa) blockers. For this reason, a literature review of the most important csDMARDs combination and bDMARDs combination studies has been deployed. The results showed that the triple csDMARDs therapy approach is more effective and less expensive. In addition, workers' productivity is higher than any other treatment options for RA. Triple-therapy constitutes a smart, efficacious, and significantly cheaper choice for RA therapeutic management.

Influence of therapeutic drugs on different manifestations of renal involvement in 907 Chinese patients with ankylosing spondylitis .

There is no systematic or large-scale study in the published literature in which the relationship between drug therapies and renal involvement in ankylosing spondylitis (AS) has been rigorously evaluated. In addition, the sensitivity of the kidneys to drugs varies significantly between races and regional populations. Therefore, the aim of the present study was to investigate the impact of drugs on renal involvement in Chinese AS patients. The clinical characteristics and biochemical data of 907 AS patients were collected and analyzed, and the differences between patients who had received drugs and those who had not were analyzed using intergroup comparisons to screen out confounding factors. Multivariate logistic regression analysis that corrected for the confounding factors explored the impact of the AS therapeutic drugs on the clinical manifestations of renal involvement. Renal involvement in Chinese AS patients increased significantly following non-steroidal anti-inflammatory drug (NSAID) or conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy, and combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor. For AS patients, NSAID monotherapy increased the probability of hematuria 2.4-fold and the probability of mixed manifestations of renal involvement 3.0-fold. csDMARD monotherapy increased the probability of proteinuria 2.4-fold; combination therapy with NSAIDs, csDMARDs, and TNF-α inhibitor increased the probability of hematuria 4.1-fold. In addition, the study found that TNF-α inhibitor monotherapy and combination therapy with NSAIDs or csDMARDs caused no apparent impact on renal involvement in AS patients. NSAID or csDMARD monotherapy may significantly increase renal involvement in Chinese AS patients. Combination therapy with TNF-α inhibitor with NSAIDs and csDMARDs should be used prudently.

THU0099 THE TIME REQUIRED TO ESCALATE THE DOSAGE OF METHOTREXATE TO THERAPEAUTIC LEVELS AFFECTS THE TREATMENT SUCCESS ACHIEVED DURING PHASE I OF THE TREATMENT ALGORITHM FOR RHEUMATOID ARTHRITIS RECOMMENDED BY THE EUROPEAN LEAGUE AGAINST RHEUMATISM

Background:In the treatment of rheumatoid arthritis (RA), methotrexate (MTX) monotherapy is undoubtedly the most cost-effective therapy available. However, no clear evidence exists for the adopted method of MTX usage, except for guidelines that have been formulated using empirical knowledge.Objectives:We aimed to retrospectively evaluate the treatment method used to administer MTX in order to identify factors influencing the success rate of MTX treatment in phase I of the European League Against Rheumatism (EULAR) recommendation in the treatment algorithm of RA.Methods:A total of 520 RA patients were considered for inclusion in this study, of whom 183 were eligible as they had been treated with MTX monotherapy from 2013 to 2018. The exclusion criteria included the following: unknown MTX prescription details (200 cases), deviation from the treatment algorithm i.e. use of a combination of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) before MTX therapy (4 cases), and a long duration of MTX escalation that deviated from the treat-to-target concept (133 cases).Patients who received csDMARD monotherapy (including switching between csDMARDs) prior to MTX monotherapy were not excluded.The primary outcome was failed MTX monotherapy with transition to phase II.The escalation time to the required maximum therapeutic dose of MTX and the lower limit of the required maintenance therapeutic dose that resulted in successful MTX monotherapy was determined using the receiver operating characteristic (ROC) curve. Accordingly, previous results obtained from ROC curve analyses were categorized into two groups for regression analysis: patients who tolerated MTX monotherapy and those who failed MTX monotherapy.We performed a regression analysis on the background factors observed during their first visit to our department and two previously identified factors. The background factors included prognostically unfavourable factors related to joint destruction despite RA treatment (i.e. rheumatoid factor [RF] levels, anti-citrullinated peptide antibody [ACPA] levels, acute phase reactant levels, swollen joint counts, joint damage, and disease activity).Results:The background factors that were statistically different were age at onset, RF levels, ACPA levels, current dose and continuity of MTX therapy, glucocorticoid (GC) use, and time until first DMARD use. After this analysis, we determined to exclude GC use from subsequent analyses as it was found to be statistically different between age groups.Using the ROC analysis, we found that the escalation time to the maximum dose of MTX was 2.07 weeks. Further, logistic regression analysis was used to analyse each of the previously reported statistically significant factors. Statistical differences were observed in the age at onset and the escalation time of initial MTX induction therapy.We also performed a backward stepwise logistic regression analysis on the previous two factors and conventional risk factors related to joint destruction with RA treatment. Statistical difference was observed in the escalation time of initial MTX induction therapy.Furthermore, propensity score matching was performed by analysing the previously mentioned influencing factors and prognostically unfavourable factors of joint destruction using a backward stepwise logistic regression analysis. We identified statistical difference in the escalation time of MTX induction therapy (odds ratio: 1.957 [95% confidential interval: 1.036-3.697], p=.039).Conclusion:These results suggest that rapid escalation to the required MTX therapeutic dose, within 2.07 weeks, during initial RA treatment can shorten the time required to achieve the treatment target. By doing this, RA patients on MTX therapy in phase I may achieve a greater treatment responsive. Thus, the short escalation time is an important factor influencing successful MTX monotherapy in the RA treatment algorithm.Disclosure of Interests:None declared

Treatment strategies are more important than drugs in the management of rheumatoid arthritis.

The treatment of inflammatory arthritides has been changed dramatically in the past two decades with the introduction of the biological (b) disease-modifying anti-rheumatic drugs (DMARDs) as well as the targeting synthetic (ts) DMARDs that can be used as monotherapy or in combination with conventional synthetic (cs) DMARDs. The concept of treat to target (T2T) and tight control monitoring of disease activity represents a therapeutic paradigm of modern rheumatology. In rheumatoid arthritis (RA), this treatment approach has proven to be effective in many clinical trials and is now a well-established approach. The most common treatment strategies rely on the combination of csDMARDs (mainly methotrexate, sulfasalazine and hydroxychloroquine). This comes from different studies which compare the outcomes of combination therapies versus csDMARD monotherapy or versus methotrexate plus biologics in early RA patients. Here, we review the literature of the most important T2T studies for RA patients. The results showed that a tight control strategy appears to be more important than a specific drug to control RA. T2T approach aiming for remission or low disease activity can be achieved in early RA patients using less expensive drugs in comparison to newer drugs and this may need to be recognised in the future recommendations for the management of RA. KEY POINTS: • Tight-control and treat-to-target (T2T) strategies are the cornerstone in achieving remission or low disease activity in rheumatoid arthritis (RA) • A plethora of clinical trials has confirmed the efficacy of csDMARDs when the tight-control and T2T strategies are applied • T2T and tight-control strategies are a less expensive option in comparison to newer drugs and may be recognised in the future recommendations for the management of RA. • Treatment decisions and strategies are more important than just the drugs.

PMS36 BUDGET IMPACT ANALYSIS OF TRIPLE THERAPY AFTER FAILURE OF METHOTREXATE FOR THE TREATMENT OF RHEUMATOID ARTHRITIS IN FRANCE

Whilst the advent of new expensive biotherapies, such as Etanercept for the treatment of rheumatoid arthritis, has improved patient outcomes and reduced the costs of disability and hospitalization, direct drug costs have become the main cost driver for this chronic inflammatory and disabling disorder and pushed overall costs up in the last 20 years. Triple csDMARDs therapy (TT) was proven to be non-inferior to the biotherapy Etanercept in the treatment of rheumatoid arthritis. The aim of this analysis was to estimate the financial consequences of increasing the use of Triple csDMARDs therapy prior to biotherapy in France. A budget impact model was developed to estimate the impact on direct healthcare costs of increasing use of TT for adults with moderate to severe disease activity after a failure of csDMARD monotherapy (Methotrexate) over three years from the French National Health Insurance perspective. French epidemiological data and published trial results were used to calculate the model inputs. We assumed that the annual uptake rates in the eligible incident population (n=2,500) for TT prescription were 50%, 65% and 80% in the first, second and third years. Total costs (€, 2018) were calculated based upon six-monthly assessments of treatment response. Deterministic sensitivity analyses were performed. The cumulative budget savings over a three-year period following the increase in prescription of TT was €51 million (41% of total costs), with approximately 4875 patients being prescribed TT after csDMARD monotherapy failure. This estimation was very sensitive to the TT uptake rate. An increased use of Triple csDMARDs Therapy, prior to biotherapy, is neither clinically inferior nor less safe and would result in a reduction of overall healthcare expenditure in rheumatoid arthritis for the French National Health Insurance. This analysis was limited, since the model did not consider non-compliance and dose de-escalation rates.

Assessing disease severity in bio-na\xefve patients with RA on treatment with csDMARDs: insights from the Corrona Registry

IntroductionThis study aimed to characterize disease burden among patients with rheumatoid arthritis (RA) with moderate-to-high disease activity who had received conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) monotherapy for ≥ 6 months but had not advanced to a biologic therapy.MethodsPatients enrolled in the US Corrona RA Registry between June 1, 2014, and January 30, 2018, with 6 months of continuous csDMARD monotherapy, with moderate-to-high disease activity, who remained biologic naive, and who had ≥ 1 follow-up visit were identified. Disease activity was assessed among patients with a 6-month follow-up visit (± 3 months). Descriptive statistics were used to compare demographics and disease characteristics between patients with or without treatment advancement.ResultsThe study included 409 patients with a disease activity assessment at 6 months (mean (SD) age 65.9 (12.6) years; mean duration of csDMARD therapy 407 (221) days). Of those patients, more than half (54%, n = 219) remained in moderate-to-high disease activity. Patients remaining in moderate-to-high vs. remission-to-low disease activity had higher baseline swollen (6.1) and tender joint counts (6.8). Over the 6-month period, treatment advancement occurred in 29% of patients. Those who advanced treatment (n = 118) vs. did not advance treatment (n = 291) were younger, had a shorter duration of RA, had higher disease activity, and reported higher levels of pain and fatigue.ConclusionsThe substantial number of patients with persistent moderate-to-high disease on csDMARDs over a 6-month period and who did not advance treatment indicates that there is considerable need for a treat-to-target approach to care for patients with RA.Key Points•For patients with RA and an inadequate response to treatment with initial csDMARD monotherapy, guidelines recommend treatment advancement; however, this may not be occurring in real-world clinical settings.•In the current study, a substantial proportion of patients (54%) on csDMARDs had persistent moderate-to-severe disease activity at the 6-month (± 3 months) follow-up visit; however, only 29% of patients had their medication treatment advanced, indicating that there is considerable need for a treat-to-target approach to care for patients with RA.•Patients with younger age, shorter RA duration, and higher disease activity were more likely to have their medication treatment advanced, which suggests that potentially more aggressive treatment of disease activity is needed across the whole RA population.

Persistence of tumor necrosis factor inhibitor or conventional synthetic disease-modifying antirheumatic drug monotherapy or combination therapy in psoriatic arthritis in a real-world setting

This study described treatment patterns in a psoriatic arthritis (PsA) patient registry for new or ongoing tumor necrosis factor inhibitor (TNFi) monotherapy, conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, or TNFi/csDMARD combination therapy. This retrospective analysis included adults with PsA who enrolled in the Corrona PsA/spondyloarthritis registry between March 21, 2013 (registry initiation), and January 31, 2017, and received an approved TNFi and/or csDMARD as “existing use” starting before registry entry or “initiated use” starting on/after registry entry. Therapy persistence was defined as index therapy use for ≥ 12 months without a treatment gap of ≥ 30 days. Among the evaluable patients with existing TNFi monotherapy (n = 251), csDMARD monotherapy (n = 225), and combination therapy (n = 214), 93, 87, and 87% were persistent for ≥ 12 months, and another 6, 5, and 5%, respectively, had no change with < 12 months of follow-up after first use. Among evaluable patients who initiated use of TNFi monotherapy (n = 26), csDMARD monotherapy (n = 35), and combination therapy (n = 15), 50, 43, and 53% were persistent for ≥ 12 months, and another 27, 20, and 20%, respectively, had no change with < 12 months of follow-up after first use. After initiation of index therapy, most changes (19–27% of patients) were discontinuation; 4–13% switched biologic therapy during follow-up. The results of this analysis of real-world treatment patterns in a PsA patient registry suggest that nonpersistence for TNFi monotherapy, csDMARD monotherapy, or TNFi/csDMARD combination therapy occurs more commonly after initiation of therapy than in patients with existing therapy. Trial registration: NCT02530268.

Minimal disease activity and impact of disease in psoriatic arthritis: a Spanish cross-sectional multicenter study

BackgroundPatients with psoriatic arthritis (PsA) experience functional impairment and reduced quality of life, and thus patient global assessment in PsA is explained mainly by the physical, but also by the psychological, aspect of the disease. To assess the prevalence of minimal disease activity (MDA) in Spanish patients with PsA, we examined their characteristics and the association between MDA and the impact of the disease as assessed by the PsA Impact of Disease (PsAID) questionnaire.MethodsA cross-sectional multicenter study was carried out in patients who fulfilled the Classification for Psoriatic Arthritis (CASPAR) criteria with at least 1 year of disease duration, and who were treated with biological or conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) according to routine clinical practice in Spain. Patients were considered in MDA if they met at least 5/7 of the MDA criteria. The association between MDA and the recently developed PsAID questionnaire was also recorded.ResultsOf 227 patients included, 133 (58.6%) were in the MDA state (52% with antitumor necrosis factor (anti-TNF)α monotherapy, 24% with csDMARD monotherapy, and 24% with anti-TNFα in combination with csDMARD). Using multivariate logistic regression analysis, male gender (odds ratio (OR) 2.74, p = 0.001), a sedentary lifestyle (OR 3.13, p = 0.002), familial history of PsA (OR 0.38, p = 0.036), C-reactive protein (CRP) level (OR 0.92, p = 0.010), and use of corticoids (OR 0.33, p = 0.007) were considered features related to MDA. MDA patients had a significantly lower impact of the disease according to PsAID (mean total score (SD): MDA 3.3 (3.1) vs. non-MDA 7.1 (5.2); p < 0.001).ConclusionsNearly 60% of Spanish PsA patients achieve MDA in routine clinical practice. MDA remains one of the most useful therapeutic targets for PsA since patients who reached this state also had a significantly lower impact of disease according to PsAID.

DAS steered therapy in clinical practice; cross-sectional results from the METEOR database.

BackgroundLittle is known on how well targeted treatment, for instance targeting towards low DAS, is implemented in clinical practice. Our aim was to evaluate treatment adjustments in response to DAS in RA patients in clinical practice.MethodsWe used data from one referral centre, multiple rheumatologists, from the METEOR database. Generalized Estimating Equations (GEE) were used to assess whether in case of non-low disease activity (DAS > 2.4) treatment intensifications in DMARD therapy occurred ((change or increase in dose or number of DMARDs, including synthetic (s)DMARDs, biologic (b)DMARDs and corticosteroids compared to the visit before)). Determinants of not intensifying the treatment when DAS > 2.4 were investigated using GEE.ResultsFive thousand one hundred fifty-seven registered visits of 1202 patients were available for the analyses. A DAS > 2.4 was weakly (OR: 1.19; 95 % CI 1.07–1.33) associated with a treatment intensification. In 69 % (n = 3577) of the visits patients were in low disease activity. In 66 % (n = 1028) of the visits with DAS > 2.4 treatment was not intensified. These patients had a higher tender joint count and received more often methotrexate plus a bDMARD, or csDMARD monotherapy, as compared to patients that received treatment intensification.ConclusionIn the majority of visits in the METEOR database patients were already in a state of low disease activity, reflecting appropriate treatment intensity. When DAS was greater than 2.4, treatment was often not intensified due to high tender joint count or specific treatment combinations. This data suggest that while aiming for low DAS, physicians per patient weigh whether all DAS elements indicate disease activity or will respond to DMARD adjustment or not, and make treatment decisions accordingly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-0878-1) contains supplementary material, which is available to authorized users.