Oral Disease-modifying Antirheumatic Drugs Research Articles

Non-Invasive Assessment of Micro- and Macrovascular Function after Initiation of JAK Inhibitors in Patients with Rheumatoid Arthritis.

Janus kinase (JAK) inhibitors constitute a novel class of oral biologic disease-modifying antirheumatic drugs for patients with rheumatoid arthritis (RA). However, their use has been associated with increased risk of major cardiovascular events. We investigated whether treatment with JAK inhibitors exerts significant alterations in the micro- and microvasculature in RA patients. Thirteen patients with RA initiating treatment with JAK inhibitors were prospectively studied. Eventually, data from 11 patients who completed the study were analyzed. Procedures were performed at baseline and 3 months after treatment. Nailfold videocapillaroscopy was applied to detect alterations of the dermal capillary network. Participants underwent 24 h ambulatory blood pressure monitoring (Mobil-O-Graph device) for the assessment of blood pressure (both brachial and aortic) and markers of large artery stiffening [pulse wave velocity (PWV), augmentation index] throughout the whole 24 h and the respective day- and nighttime periods. Carotid intima-media thickness was assessed with ultrasound. Three-month treatment with JAK inhibitors was not associated with any differences in brachial and aortic blood pressure, arterial stiffness, and carotid atherosclerosis, with the only exception of nighttime PWV, which was significantly elevated at follow-up. However, three-month treatment with JAK inhibitors induced significant microvascular alterations and increased the total number of capillaroscopic abnormalities. Three-month treatment with JAK inhibitors may exert significant effects on microcirculation as assessed with nailfold videocapillaroscopy, whereas macrovascular structure and function appears largely unaffected. Further research toward this direction may add substantial information to the available literature regarding cardiovascular aspects of JAK inhibitors in RA.

Association of serum IL12 with clinical and biochemical parameters in a cohort of diagnosed rheumatoid arthritis patients on oral conventional synthetic disease modifying anti-rheumatic drugs.

To determine the association of serum interleukin-12 levels with disease progression in active rheumatoid arthritis patients on oral conventional synthetic disease-modifying anti-rheumatic drugs. The case-control study was conducted at the Army Medical College, Rawalpindi, in collaboration with the Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January to December 2022, and comprised rheumatoid arthritis patients or either gender aged 18-75 years who were placed in group I, while group II comprised healthy controls. Demographic and clinical data was noted, and 2ml blood samples were drawn from each subject. The serum was separated and analysed using sandwich enzyme-linked immunosorbent assay to quantify serum interleukin-12 levels. Data was analysed using SPSS 22. Of the 150 subjects, 75(50%) were in group I; 27(36%) males and 48(64%) females with overall mean age 45.70±11.70 years. There were 75(50%) subjects in group II; 37(49.3%) males and 38(50.7%) females with overall mean age 31.70±7.70 years. Serum interleukin-12, erythrocyte sedimentation rate and C-reactive proteinquantitative levels were significantly higher in group I compared to group II (p<0.05). Smoking, positive family history of rheumatoid arthritis in a first-degree relative and history of consanguinity were identified as risk factors though they were not statistically significant (p>0.05). In group I (n=75), out of total study subjects, only 55(73.3%) cases belonged to the predominant castes, namely Awan, Rajput, Pathan, Araeen, Bhatti, Malik, Mughal, Sudhan, Chaudary, and Jutt. These individuals showed significantly higher mean serum interleukin-12 levels compared to patients of other castes in the same group. Mean serum interleukin-12 levels were higher in rheumatoid arthritis patients despite being on oral conventional synthetic disease-modifying anti-rheumatic drugs.

JAK Inhibitors in Rheumatoid Arthritis

JAK inhibitors (JAKi) are targeted, small-molecule, disease-modifying therapies that are the newest class of treatments to emerge for the management of rheumatoid arthritis (RA) and the first oral disease-modifying anti-rheumatic drugs (DMARD) to demonstrate comparable clinical efficacy to biological DMARDs (bDMARD). In the UK there are four JAKi licensed for the treatment of RA (baricitinib, tofacitinib, upadacitinib, and filgotinib) and recent years have seen an explosion in their use. Clinical trial evidence supports their efficacy in a range of RA cohorts including DMARD-naïve patients and those with treatment-refractory disease. JAKi are associated with increased risk for infection, particularly herpes zoster virus reactivation, cytopenias, and hyperlipidaemia. In older patients with cardiovascular risk factors, post-marketing data suggest increased risk for malignancy, venous thromboembolism (VTE), and major cardiovascular events (MACE) with JAKi. This review article discusses the mechanism of action of JAKi and the evidence for their efficacy and side effect profile.

Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review.

There is an increasing trend of malignancy worldwide. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstones for the treatment of immune-mediated inflammatory diseases (IMIDs), but risk of malignancy is a major concern for patients receiving DMARDs. In addition, many IMIDs already carry higher background risks of neoplasms. Recently, the black box warning of malignancies has been added for Janus kinase inhibitors. Also, the use of biologic DMARDs in patients with established malignancies is usually discouraged owing to exclusion of such patients in pivotal studies and, hence, lack of evidence. In contrast, some conventional synthetic DMARDs (csDMARDs) have been reported to show antineoplastic properties and can be beneficial for patients with cancer. Among the csDMARDs, chloroquine and hydroxychloroquine have been the most extensively studied, and methotrexate is an established chemotherapeutic agent. Even cyclosporine A, a well-known drug associated with cancer risk, can potentiate the effect of some chemotherapeutic agents. We review the possible mechanisms behind and clinical evidence of the antineoplastic activities of csDMARDs, including chloroquine and hydroxychloroquine, cyclosporine, leflunomide, mycophenolate mofetil, mycophenolic acid, methotrexate, sulfasalazine, and thiopurines. This knowledge may guide physicians in the choice of csDMARDs for patients with concurrent IMIDs and malignancies.

Compliance with oral disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a Colombian experience

IntroductionThe use of disease modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) is essential in order to achieve and maintain adequate disease control, and thus preventing irreversible functional damage. However, the rate of adherence to drug therapy has been reported to be between 20% and 107%. This variability may be due to the measurement methods used in the different studies. ObjectiveTo test the overall medication adherence to oral treatment with DMARD in patients with RA using the self-report Spanish version Compliance-Questionnaire-Rheumatology (CQR) and to identify potential factors associated with non-adherence. MethodsA cross-sectional descriptive study was conducted that included patients older than 18 years with RA diagnosed according to the ACR-EULAR 2010 criteria. They also had to have been prescribed oral DMARD for the previous 3 months, and had been seen by a rheumatologist in the last year. Patients completed the CQR to assess adherence, and were asked about disease knowledge, perception about treatment, side effects, Charlson Comorbidity Index, global index of social support, number of medications and DMARD prescribed, access to health resources, and disease activity measured by DAS 28 or CDAI. Good adherence was defined as a cut-off point of CQR > 80 or non-activity (remission or low activity). In the search for factors associated with adherence, the data were analysed using means of median and interquartile range, as well as frequencies and proportions. The comparison between adherent and non-adherent groups was performed using absolute comparisons, with the Mann-Whitney test for continuous, and chi-squared (for expected values> 5), or Fisher (for expected values ​​<5) tests for categorical variables, taking as a level of significance a value of p < 0.05. OR and their respective 95% confidence intervals (95% CI) were used. ResultsOf 170 participants included, 50% (n = 85) had a value greater than 80% (good drug adherence). Most patients had remission (60.6%) or low disease activity (17%). The subsequent analysis showed statistically significant association between adherence measured by CQR and the number of friends (P = .0012). An association was also found between disease activity as an indirect indicator of adherence and the global social support index (P = .004). ConclusionThis study found a similar level of adherence to that reported in other populations, which could be due to the behaviour of our population, although the authors perceived difficulties reported by patients in understanding the statements of the questionnaire at all levels of education. Only the social support variables had a statistically significant relationship with adherence, which had also been described in the literature. Further studies are required to evaluate the operational characteristics of the CQR in our population.

Reproductive Tract Infection Among Women Suffering From Rheumatoid Arthritis in India: A Clinical-Based, Cross-Sectional Study

Background: Much research has been done on reproductive tract infections (RTIs), but no study exists about RTIs among rheumatoid arthritis women. Objectives: This study investigated the prevalence and risk factors of RTIs among reproductive-aged women with rheumatoid arthritis in Pune, India. Methods: This clinical-based, cross-sectional study enrolled a sample of 400 consenting Indian women aged 15 -49 years with a history of at least three months’ rheumatoid arthritis referring to a popular community center. Patients were interviewed comprehensively using previously validated relevant questionnaires. Women underwent gynecological examinations and vaginal smears (wet mount) by a microbiologist to diagnose candidiasis, bacterial vaginosis, and trichomoniasis. Syphilis serological testing was performed for the study population. Results: The prevalence obtained was 39.3%. Infection with bacterial vaginosis was 32.0%, Candidiasis 6.5%, and trichomoniasis 0.8%. Syphilis seroconversion was not observed. Adjusting for confounding factors in logistic regression showed that four factors remained significant, including age under 30 years [AOR: 2.4, 95% CI: 1.2 - 4.9], living in a crowded and small one-room house [AOR: 2.5, 95% CI: 1.2 - 5.1] , improper linen for menstruation bleeding [AOR: 1.9, 95% CI: 1.1 - 3.3], and oral disease-modifying anti-rheumatic drugs [AOR: 3.96, 95% CI: 1.9 - 7.9]. Conclusions: This study demonstrated a large burden of RTIs in women suffering from rheumatoid arthritis. Regular screening algorithms for RTIs are urgently required to prevent neglect and improve overall standard care in rheumatology practice. The presence of an oral disease-modifying anti-rheumatic drug as a risk factor shows that more investigation is necessary in this case.

Adherencia a medicamentos orales en pacientes con artritis reumatoide, una experiencia colombiana

IntroductionThe use of disease modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) is essential in order to achieve and maintain adequate disease control, and thus preventing irreversible functional damage. However, the rate of adherence to drug therapy has been reported to be between 20% and 107%. This variability may be due to the measurement methods used in the different studies. ObjectiveTo test the overall medication adherence to oral treatment with DMARD in patients with RA using the self-report Spanish version Compliance Questionnaire on Rheumatology (CQR) and to identify potential factors associated with non-adherence. MethodsA cross-sectional descriptive study was conducted that included patients older than 18 years with RA diagnosed according to the ACR-EULAR 2010 criteria. They also had to have been prescribed oral DMARD for the previous 3 months, and had been seen by a rheumatologist in the last year. Patients completed the CQR to assess adherence, and were asked about disease knowledge, perception about treatment, side effects, Charlson Comorbidity Index, global index of social support, number of medications and DMARD prescribed, access to health resources, and disease activity measured by DAS 28 or CDAI. Good adherence was defined as a cut-off point of CQR>80 or non-activity (remission or low activity). In the search for factors associated with adherence, the data were analysed using means of median and interquartile range, as well as frequencies and proportions. The comparison between adherent and non-adherent groups was performed using absolute comparisons, with the Mann-Whitney test for continuous, and chi-squared (for expected values >5), or Fisher (for expected values <5) tests for categorical variables, taking as a level of significance a value of P<.05. OR and their respective 95% confidence intervals (95% CI) were used. ResultsOf 170 participants included, 50% (n=85) had a value greater than 80% (good drug adherence). Most patients had remission (60.6%) or low disease activity (17%). The subsequent analysis showed statistically significant association between adherence measured by CQR and the number of friends (P=.0012). An association was also found between disease activity as an indirect indicator of adherence and the global social support index (P=.004). ConclusionsThis study found a similar level of adherence to that reported in other populations, which could be due to the behaviour of our population, although the authors perceived difficulties reported by patients in understanding the statements of the questionnaire at all levels of education. Only the social support variables had a statistically significant relationship with adherence, which had also been described in the literature. Further studies are required to evaluate the operational characteristics of the CQR in our population.

Pop a pill or give myself a shot? Patient perspectives of disease-modifying anti-rheumatic drug choice for rheumatoid arthritis.

To assess how patients with rheumatoid arthritis (RA) decide whether to add oral disease-modifying anti-rheumatic drugs (DMARDs) versus injectable biologic DMARDs when methotrexate response is inadequate. Using nominal group technique (NGT), RA patients answered the question "What sort of things are important to you when you make a decision between adding pills versus injectable medications to treat rheumatoid arthritis when methotrexate fails to control RA disease activity?" Patients nominated, discussed, and voted for the responses. Forty-seven RA patients participated: Birmingham (n=6 NG; 21 patients) and New York City (n=4 NG; 26 patients). They were predominantly female (85%), 70% white, with a mean age of 64.5 years and 58% had>10-year RA duration. Present/past DMARDs included methotrexate only in 6%, other traditional DMARDs in 15%, glucocorticoids in combination with traditional DMARDs in 11%, and biologics and/or Jak-kinase inhibitors in 68% of participants. Voted domains in order were: (1) efficacy/effectiveness and the onset/mode of action (78/282 votes); (2) side effects/fear of side effects (84/282 votes); (3) cost including out of pocket, co-payments and patient responsibility (54/282 votes); (4) convenience/frequency of use (27/282 votes); (5) doctor's opinion (20/282 votes); (6) other drugs/comorbidity/other patient's experience/effects on other people (3/282 votes); (7) fear of needles (8/282 votes); and (8) newness of the medication (8/282 votes). We identified the patient perspective regarding the choice between adding oral versus injectable DMARD once methotrexate failed to control RA disease activity. This knowledge can help in shared decision-making for DMARD choice in RA treatment.

O27 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

Abstract Background In 2017, a new class of oral disease modifying anti-rheumatic drugs (DMARDs), janus kinase inhibitors (JAKi), were licensed for rheumatoid arthritis (RA): baricitinib and tofacitinib. In the UK, they are approved for use in patients with high disease activity with or without methotrexate, following failure of conventional synthetic (cs) DMARDs or biologic DMARDs, the latter when rituximab is contraindicated. As a new therapy option, it is currently unclear how and when these drugs are being prescribed in patients with RA. This analysis aims to describe the characteristics of patients starting JAKi and registered with the BSRBR-RA. Methods The BSRBR-RA aims to capture exposure and outcome data in patients with RA receiving biologics, biosimilars and targeted synthetic DMARDs. At the start of therapy, demographic and clinical data, including past treatment data, are collected. Characteristics of all patients receiving a JAKi for the first time with data recorded in the BSRBR-RA up to 31/03/2019 are described. Results To 31/03/2019, 698 patients in the BSRBR-RA have been treated with a JAKi; 596 patients baricitinib and 110 tofacitinib (Table 1). A quarter of patients received a JAKi with no prior biologic exposure; 148 (25%) baricitinib and 16 (15%) tofacitinib. Of these, 15% had a prior malignancy history. Of those with prior biologic exposure, the median number of previous biologics was 3 (IQR 2-4), the majority had prior TNFi (91%) or rituximab (51%), and 50% were receiving concurrent methotrexate. Conclusion To date, more patients have been recruited starting baricitinib than tofacitinib, likely owing to the later licensing of tofacitinib. Two groups are emerging with a quarter of patients receiving JAKi immediately after csDMARDs and a majority as a later stage alternative following multiple biologics. Further recruitment and follow-up patients will allow for analysis of real-world safety and effectiveness, but differences in patient characteristics will need to be considered in any comparative effectiveness analyses. Disclosures L. Kearsley-Fleet None. R. Davies None. K. Watson None. M. Lunt None. K.L. Hyrich Honoraria; AbbVie. Grants/research support; UCB, Pfizer, BMS.

Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review.

There have been several episodes of viral infection evolving into epidemics in recent decades, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest example. Its high infectivity and moderate mortality have resulted in an urgent need to find an effective treatment modality. Although the category of immunosuppressive drugs usually poses a risk of infection due to interference of the immune system, some of them have been found to exert antiviral properties and are already used in daily practice. Recently, hydroxychloroquine and baricitinib have been proposed as potential drugs for SARS-CoV-2. In fact, there are other immunosuppressants known with antiviral activities, including cyclosporine A, hydroxyurea, minocycline, mycophenolic acid, mycophenolate mofetil, leflunomide, tofacitinib, and thalidomide. The inherent antiviral activity could be a treatment choice for patients with coexisting rheumatological disorders and infections. Clinical evidence, their possible mode of actions and spectrum of antiviral activities are included in this review article.Lay summaryImmunosuppressants often raise the concern of infection risks, especially for patients with underlying immune disorders. However, some disease-modifying antirheumatic drugs (DMARDs) with inherent antiviral activity would be a reasonable choice in the situation of concomitant viral infections and flare up of autoimmune diseases. This review covers DMARDs of treatment potential for SARS-CoV-2 in part I, and antiviral mechanisms plus trial evidence for viruses other than SARS-CoV-2 in part II.

Association of Medication Beliefs, Self-efficacy, and Adherence in a Diverse Cohort of Adults with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) patients' adherence to disease-modifying antirheumatic drugs (DMARD) is often suboptimal. We examined associations among medication beliefs, self-efficacy, and adherence to medications in RA. Data were from a longitudinal observational cohort of persons with RA. Subjects completed telephone interviews on self-reported adherence, self-efficacy, demographics, and the Beliefs about Medicines Questionnaire (BMQ), which assesses beliefs in necessity and beliefs about taking medication. Bivariate and multivariate logistic regression identified correlates of poor adherence to synthetic DMARD and prednisone as well as to biologic therapy, including medication concerns and necessity. There were 362 patients who reported taking a synthetic DMARD and/or prednisone. Of these, 14% and 21% reported poor adherence to oral DMARD or prednisone, and biologics, respectively. There were 64% who reported concern about taking medicines, 81% about longterm effects, and 47% about becoming too dependent on medicines. In multivariate analyses, the BMQ necessity score was independently associated with better adherence to oral DMARD or prednisone (adjusted OR 0.61, 95% CI 0.41-0.91), while self-efficacy was associated with greater odds of poor adherence to oral medications (adjusted OR 1.23, 95% CI 1.01-1.59). Beliefs in medicines and self-efficacy were not associated with adherence to biologics. In a diverse cohort of patients with RA, stronger beliefs in the necessity of medication were associated with better adherence to oral DMARD or prednisone, while higher self-efficacy was associated with poor adherence. Providers can play important roles in eliciting patient beliefs about medications to improve adherence and ultimately health outcomes.

Use of rheumatology-specific patient navigators to understand and reduce barriers to medication adherence: Analysis of qualitative findings.

ObjectiveAdherence to medications among patients with rheumatic diseases is often suboptimal. Patient navigators, individuals trained in care coordination, motivational interviewing and basic rheumatology and pharmacology, have not been employed to explore and address this issue. We piloted a single-site, single arm intervention to determine the feasibility and acceptability of using rheumatology-specific navigators to understand and reduce barriers to adherence to oral disease modifying anti-rheumatic drugs (DMARDs). We analyzed our qualitative findings from navigator-patient interactions as well as patient satisfaction with the intervention.MethodsWe recruited patients ≥18 years with a systemic rheumatic disease who initiated an oral DMARD within the prior 6 months. Navigators conducted baseline needs assessments and 2–4 week follow-up calls to understand and address issues related to medication adherence. We analyzed patient-navigator encounters qualitatively using content analysis to identify key themes related to barriers to adherence and navigator actions performed in response to the barriers described. We also categorized intentional and unintentional nonadherent behavior and assessed satisfaction with the navigator experience (range 0–5, 5 = most satisfied).Results107 rheumatology patients were followed for up to 6 months. Mean patient age was 55 years (+17) and 93% were female; 36% described one or more episode of intentional or unintentional nonadherence. The three most common themes identified as barriers to adherence were fear of adverse events (raised by 54%), concerns about medication effectiveness (43%), and challenges with medication acquisition (32%). 86% of participants described at least one adherence-related barrier. Frequent navigator actions included facilitation of patient-doctor communication (38%), medication and diagnosis education (27%), and development of individualized strategies to improve adherence (16%). Patients were satisfied with the navigator experience (mean 4.4 + 0.9).ConclusionNavigators uncovered and addressed a number of medication adherence-related concerns and patients were satisfied with the services provided.

Pharmacotherapy Pearls in Rheumatology for the Care of Older Adult Patients: Focus on Oral Disease-Modifying Antirheumatic Drugs and the Newest Small Molecule Inhibitors.

Providing safe and effective pharmacotherapy to geriatric patients with rheumatologic disorders is challenging. Multidisciplinary care involving rheumatologists, primary care physicians, and other specialties can optimize benefit and reduce adverse outcomes. Oral disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, and the small molecule inhibitors tofacitinib and apremilast have distinctive monitoring requirements and specific adverse reaction profiles. This article provides clinically relevant pearls for use of these interventions in older patients.

New antirheumatics : Advances for patients and society

The current repertoire of conventional, biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) presents wide-ranging options to help patients with inflammatory rheumatic diseases. These therapeutic possibilities have improved quality of life for many patients and also had apositive impact at the societal level. Among these positive effects are a reduction in short-term inability to work and early retirement; for paediatric patients they represent an opportunity for an almost normal school life including physical education. The development of formulations adapted to patients' needs has greatly facilitated the long-term treatment of these chronic diseases. Further additions to the therapeutic spectrum can be expected in the years to come, including new oral synthetic DMARDs. Even for rare inflammatory rheumatic diseases, various therapeutic options should be available soon, thus increasing these patients' chances of a life with significantly fewer impairments. As German trial sites are participating in many clinical trials on inflammatory rheumatic diseases, there are many opportunities to mediate patients to a trial if the approved treatment options do not prove satisfactory.

Can Patient Navigators Improve Adherence to Disease-Modifying Antirheumatic Drugs? Quantitative Findings From a Six-Month Single-Arm Pilot Intervention.

Nonadherence to disease-modifying antirheumatic drugs (DMARDs) is common, worsens during the treatment course, and results in adverse outcomes. We studied whether patient navigators (laypersons trained in care coordination, motivational interviewing, basic pharmacology, and disease management) improved oral DMARD adherence. We enrolled 107 patients ages ≥18 years with systemic rheumatic diseases who initiated an oral DMARD within 6 months. Navigators interacted with patients up to 2-4 times per week for 6 months. Patients completed validated surveys (Morisky Medication Adherence Scale [MMAS-8], Mental Health Inventory [MHI-5], Beliefs about Medicines Questionnaire, and Brief Illness Perception Questionnaire) at baseline and at 6 months. We used paired t-tests to compare baseline and 6-month outcomes. We examined the association of age, race/ethnicity, insurance, and MHI-5 with change in MMAS-8 score using multivariable linear regression. Among 107 patients enrolled, 69 (64%) completed baseline and 6-month MMAS-8 surveys. Mean ± SD age was 55 ± 16 years and 93% were female. The mean ± SD baseline MMAS-8 score was 6.7 ± 1.3 (indicating borderline adherence), and the mean ± SD MHI-5 score was 60.8 ± 9.1 (<68 suggests any depressive symptoms). After 6 months, there were no significant changes in MMAS-8 (P = 0.09) or MHI-5 (P = 0.83). Patients described fewer medication concerns (P = 0.03), but a more threatening perception of illness (P = 0.01). Our multivariable model demonstrated a small change in MMAS-8 for each 5-year increase in age (β = 0.14, P = 0.02). Our intervention resulted in no significant change in adherence from baseline. A multicenter, randomized controlled trial is needed to determine whether patient navigators are effective in maintaining adherence to DMARDs over time.

Quantity and economic value of unused oral anti-cancer and biological disease-modifying anti-rheumatic drugs among outpatient pharmacy patients who discontinue therapy.

Patients sometimes discontinue the use of expensive oral anti-cancer drug (OACD) or biological disease-modifying anti-rheumatic drug (bDMARD) therapies early, leading to medication waste if the patient has not used all dispensed medication. To determine the proportion of patients who have unused OACDs or bDMARDs after therapy discontinuation, and the quantity and economic value of these unused medications. Furthermore, patients' reasons for therapy discontinuation and their disposal method for unused medications were determined. In a retrospective follow-up study using a Dutch outpatient pharmacy database, patients (≥18 years) who did not refill an OACD or bDMARD prescription, dispensed between November 2015 and February 2016, within two weeks of the prescription end date were contacted by phone and asked about their unused medication and reasons thereof. The economic value was calculated using Dutch medication prices. Data were descriptively analyzed in STATA13. The database included 1173 patients, of whom 159 likely had discontinued therapy and were contacted. Of these, 88 patients were excluded (39 refilled, 47 missing, and 2 other). Of the 71 patients who had discontinued therapy, 39 (54.9%) had unused medications, comprising 22 OACD users (mean age 63.0 (SD ± 15.9) years, 50.0% female) and 17 bDMARD users (mean age 50.7 (SD ± 13.5) years, 47.1% female). A total of 59 packages were unused, with a total value of €60,341. Unused OACD packages and bDMARD packages had median values of €179 (IQR €24-2487) and €992 (IQR €681-1093), respectively. Patients primarily discontinued therapy due to adverse or insufficient effects. This study illustrates that more than half of patients discontinuing OACD or bDMARD therapies have unused medication. This emphasizes the need for waste-reducing interventions.

Triple Oral Therapy Versus Antitumor Necrosis Factor Plus Methotrexate (MTX) in Patients with Rheumatoid Arthritis and Inadequate Response to MTX: A Systematic Literature Review

For patients with rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX), the relative effectiveness of the combination of conventional disease-modifying antirheumatic drugs (DMARD) compared with the combination of tumor necrosis factor (TNF) inhibitors and MTX, as second-line therapy, is uncertain. The aim of this study was to compare the efficacy and tolerance of triple oral DMARD therapy versus anti-TNF agents associated with MTX in patients with RA after MTX failure. We performed a systematic search of the literature up to November 2015 in MEDLINE, Embase, the Cochrane library, and abstracts from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) meetings from 2006 to 2015. Articles were included if they were of randomized controlled trials of patients receiving triple oral combination therapy (TT; MTX + sulfasalazine + hydroxychloroquine) compared with anti-TNF agents plus MTX. Treatment effects were examined by disease activity [Disease Activity Score in 28 joints (DAS28)], ACR and EULAR response criteria, structural damage by the modified total Sharp score, and functional disability by the Health Assessment Questionnaire (HAQ). Our search identified 263 articles; only 5 fulfilled the selection criteria. Analysis of ACR and EULAR response criteria, DAS28, and modified Sharp scores favored anti-TNF agents combined with MTX. Functional disability (HAQ) and rates of adverse events did not differ between treatments. In patients with RA in whom MTX has failed, the addition of a TNF antagonist to MTX may be a valid option, with better clinical outcomes and better radiographic results in the presence of poor prognostic factors. In the absence of poor prognostic factors and/or with contraindications to biologic agents, TT retains its place in the therapeutic strategy for RA in a currently restricted economic context.

Treatment Guidelines for Rheumatologic Manifestations of Sjögren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain.

The Sjögren's Syndrome Foundation clinical practice guidelines (CPGs) are designed to improve quality and consistency of care in Sjögren's syndrome by offering recommendations for management. Management questions for the systemic manifestations of Sjögren's syndrome were posed by the CPG committee with input from patients and rheumatologists. Clinical questions were assigned to a topic review group that performed systematic reviews and data extraction and drafted guidelines. Quality of evidence and strength of recommendation were rated using the American Society of Clinical Oncology's modification of the Grading of Recommendations Assessment, Development, and Evaluation. Guideline recommendations were reviewed by a consensus expert panel (CEP) composed of 30-40 clinicians from academia and community practices, as well as registered nurses and patients, using a modified Delphi process. A CEP agreement level of 75% was set as a minimum for adoption of a guideline recommendation. Consensus was achieved for 19 recommendations; for 11 additional modules, available data were insufficient to allow a recommendation to be formulated. Of the 19 recommendations, 15 required 1 Delphi round, 2 required 2 rounds, and 2 required 3 rounds. Key recommendations include a decision tree for the use of oral disease-modifying antirheumatic drugs for inflammatory musculoskeletal pain, use of self-care measures and advice regarding exercise to reduce fatigue, and the use of rituximab in selected clinical settings for oral and ocular dryness and for certain extraglandular manifestations, including vasculitis, severe parotid swelling, inflammatory arthritis, pulmonary disease, and mononeuritis multiplex. The CPG committee strongly discouraged the use of tumor necrosis factor inhibitors for sicca symptoms and for the majority of clinical contexts in primary Sjögren's syndrome.

Long-term safety and efficacy of biosimilar infliximab among patients with inflammatory arthritis switched from reference product.

PurposeTo evaluate the efficacy and safety of the biosimilar infliximab in adult patients with inflammatory arthritis switched from reference product in our center.Patients and methodsIn April 2014, patients attending our rheumatology service for infliximab infusions were switched from reference product to the biosimilar infliximab following consent and hospital approval.ResultsAround 34 patients with inflammatory arthritis were switched from reference product to biosimilar infliximab in 2014: 50% female, mean age 55 years (standard deviation=12.9), mean disease duration 14.79 years (9.7), median duration on infliximab 57 months, and two-thirds on oral disease-modifying antirheumatic drugs. There was no difference in efficacy or safety in the first 6 months of therapy. By the end of 2015, the mean follow-up on biosimilar infliximab was 15.8 (standard deviation=6.3) months. Our results showed no significant difference in Health Assessment Questionnaire score, patient global assessment of disease activity, number of disease flares, or the medication dose between the originator and the biosimilar infliximab. However, reported pain and C-reactive protein values were significantly higher during the longer follow-up period (p=0.043, 0.001 respectively). There was no significant difference in the number of adverse events or infusion reactions during follow-up periods. Only five (14.7%) patients discontinued the biosimilar infliximab.ConclusionOur patients experienced similar efficacy and safety for managing their arthritis with the biosimilar infliximab as the reference product infliximab, but at a much lower cost.

Recent Progress in JAK Inhibitors for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. Considerable advance in the treatment of RA has been made following the advent of biological disease-modifying anti-rheumatic drugs (DMARDs). However, these biologics require intravenous or subcutaneous injection and some patients fail to respond to biological DMARDs or lose their primary response. Various cytokines and cell surface molecules bind to receptors on the cell surface, resulting in the activation of various cell signaling pathways, including phosphorylation of kinase proteins. Among these kinases, the non-receptor tyrosine kinase family Janus kinase (JAK) plays a pivotal role in the pathological processes of RA. Several JAK inhibitors have been developed as new therapies for patients with RA. These are oral synthetic DMARDs that inhibit JAK1, 2, and 3. One JAK inhibitor, tofacitinib, has already been approved in many countries. Results of phase III clinical trials using a JAK1/2 inhibitor, baricitinib, have shown feasible efficacy and tolerable safety. Both drugs are effective in patients who showed inadequate response to biological DMARDs as well as synthetic DMARDs. In addition, clinical phase III trials using filgotinib and ABT-494, specific JAK1 inhibitors, are currently underway. JAK inhibitors are novel therapies for RA, but further studies are needed to determine their risk-benefit ratio and selection of the most appropriate patients for such therapy.