Disease-modifying Antirheumatic Agents Research Articles

Reactivation of Hepatitis B Virus among Malignancy Patients Undergoing Chemotherapy: A Prospective Cohort Study

Abstract Introduction: Reactivation of hepatitis B virus (HBV) can occur in patients receiving short-term chemotherapy, long-term immunosuppressive therapy, or disease-modifying antirheumatic agents for rheumatological diseases and is more common in hepatitis B surface antigen-positive patients. However, there is a lack of data for reactivation among malignant patients undergoing chemotherapy in resolved HBV patients. Methodology: A prospective cohort study of 200 oncological patients on chemotherapy was conducted for the reactivation of the HBV for a year. Patients underwent a thorough physical examination; baseline assessment and biochemical test and test were repeated at each follow-up. Results: The majority were females and in the 40–60-year age group. Age and serum albumin levels were significantly different (P < 0.05) among the reactivated versus the nonreactivated groups. Hepatitis B reactivation was seen in 14 (7%) patients with a maximum in the rituximab therapy group (11.26%). There was no statistically significant difference in baseline ALT levels between patients who experienced reactivation and those who did not. Conclusion: In the present study population, 7% had hepatitis B reactivation. The present study identifies old age, low serum albumin, and rituximab chemotherapy as significant risk factors for reactivation. Prophylactic antiviral therapy seems to be effective as no reactivation has occurred in this group.

Performance of the QuantiFERON- TB gold test in children receiving immunosuppressive therapy for rheumatic diseases

ObjectivesThe mainstay of treatment for pediatric rheumatological disease is disease-modifying anti-rheumatic agents which are immunosuppressive in nature and increase the susceptibility to tuberculosis. The aims and objectives were to evaluate the performance of the QuantiFERON®-TB Gold test (QFT) and Tuberculin skin test (TST) to diagnose latent tuberculosis in children receiving immunosuppressive therapy for rheumatic diseases in a tertiary hospital in South India. MethodsThis was a prospective observational study. 60 consecutive children diagnosed with various rheumatic diseases attending the Paediatric Rheumatology clinic on immunosuppressive therapy were included. The QFT and TST were performed on the same day. Data regarding the demography, diagnosis, treatment received and test results were collected and analysed. ResultsAmong patients included (n = 60), two children had positive QFT and one child had positive TST. The agreement between tests was k = 0.85 and the proportion of latent tuberculosis was 5 %. All the children included were on conventional DMARDs and 3.3 % were on biological DMARDs. There was a significant decrease in the mitogen induced interferon level in children on treatment with hydroxychloroquine (p = 0.022) and a significant increase in the level in children on azathioprine (p = 0.006). Children on steroids had a lower range of mitogen-induced interferon levels. ConclusionQFT may be a more reliable test than TST for the detection of latent tuberculosis in children with rheumatic diseases receiving immunosuppressive treatment. The use of hydroxychloroquine and steroids might influence the mitogen-induced IFN-γ secretion and may interfere with the interpretation of the QFT test.

Adoption rates of recommended vaccines and influencing factors among patients with inflammatory arthritis: a patient survey.

To determine the scope of recommended vaccination uptake among patients with inflammatory arthritis (IA) receiving biologic and targeted synthetic disease-modifying antirheumatic agents (bDMARDs and tsDMARDs, respectively) and to determine factors, which influence their decision and are subject to modification. A single-center, cross-sectional study was conducted including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) on bDMARDs or tsDMARDs. Demographic, anthropometric, and clinical parameters were analyzed. Disease activity was determined using the validated indices DAS28-CRP and CDAI for RA and peripheral PsA, whereas BASDAI and ASDAS for AS and axial PsA. Patients completed a questionnaire with predefined response options assessing their vaccination status and attitudes about receiving a COVID-19 vaccination. A total of 201 patients with inflammatory joint diseases were included in the study, with a mean age of 54.6 (± 8.6) years and a disease duration of 11 (± 14.4) years. More than one-third of the study group had received full vaccination against SARS-CoV-2, with the majority (68.1%) receiving the BNT162b2 vaccine. The proportion of patients who had received recommended pneumococcal and influenza vaccinations and regular reimmunizations against diphtheria and tetanus was low, with only 13.9% (n = 28), 1.5% (n = 3), and 44.8% (n = 90), respectively. Patients who had a preceding discussions with a rheumatologist were more likely to get vaccinated. Considering the suboptimal vaccination rates and the prevalent uncertainty among individuals with IA in Bulgaria, there is an urgent need to devise novel strategies to promote vaccination uptake and enhance patient awareness. These strategies aim to educate patients about their autoimmune condition, as well as emphasize the safety and efficacy of vaccines.

Efficacy of rituximab in difficult to treatment patients with polymyositis

Inflammatory myopathies are a heterogeneous group of diseases rarely encountered in clinical practice. They primarily involve the transverse striated muscles, and in some cases there is also extramuscular involvement of the skin, lungs, joints, esophagus, heart. Acute forms of myositis, which are the most common, are associated with viral diseases and usually resolve spontaneously. Chronic forms usually have a subacute onset and unknown etiology. The presence of different clinical phenotypes and courses is associated with diversity in autoantibody production. Historically, the treatment of refractory forms of polymyositis and dermatomyositis has undergone significant dynamics. Data from various studies have been published that show a significant reduction in the symptoms of inflammation, but unfortunately some of these disease-modifying treatments could not be established in rheumatology practice as sufficiently effective. Limiting factors are the retrospective nature of these studies, as well as different inclusion and exclusion criteria. However, in recent years, more and more data have emerged that present rituximab as one of the promising molecules for the treatment of patients refractory to conventional synthetic disease-modifying antirheumatic agents We present a clinical case of a 40-year-old Caucasian man with onset of the disease – fever, asthenodynamia, muscle pain and weakness, pericardial and pleural effusions. The patient was treated with glucocorticoids, methotrexate, pulse therapies with methylprednisolone and cyclophosphamide, as well as pulse therapy with intravenous immunoglobulins. Due to the temporary effect of the treatment and the relapse of the disease, the patient was started on mycophenolate mofetil therapy (instead of methotrexate). However, a new peak in disease activity was reported, necessitating resumption of pulse therapies with methylprednisolone and cyclophosphamide. Due to the refractory course of the disease, the patient was treated with rituximab after signed informed consent. A significant reduction in disease activity and a good clinical and therapeutic effect were reported.

Withdrawal of biologic therapy in juvenile idiopathic arthritis due to remission: predictors of flare and outcomes

ABSTRACT Objectives To investigate patients who flared after discontinuation of biological disease-modifying anti-rheumatic agents (bDMARDs) and identify risk factors associated with flare. Methods A multicenter study evaluating systemic and non-systemic juvenile idiopathic arthritis (sJIA and non-sJIA) patients whose bDMARDs were ceased after remission. Results A total of 101 patients whose bDMARDs were ceased after remission was evaluated. Children with sJIA had the lowest risk of flare and 11.1% of 36 sJIA patients experienced flare after a median of 9 (4–24) months of bDMARDs cessation with three of them flaring in the first year. High leukocyte counts in sJIA patients were associated with inactive disease at 1-year after the start of treatment (p = 0.004). In the non-sJIA group, 46.1% patients experienced flare after a median of 7 (1–32) months of biologic cessation, and of these, 25 flared in the first year. Antinuclear antibody positivity (p = 0.02), earlier disease onset (p = 0.03), long disease duration (p = 0.01), and follow-up (p = 0.02) and extended time from diagnosis to first biological onset (p = 0.03) were more common among patients with flare. Conclusions When considering discontinuation of bDMARDs, it should be kept in mind that the risk of exacerbation requiring re-initiation therapy is quite significant within the first year after discontinuation of therapy.

Disease-Modifying Antirheumatic Drugs in the Treatment of Autoimmune Inner Ear Disease: A Systematic Review and Meta-Analysis of Auditory and Vestibular Outcomes.

To answer the following question: In patients with primary autoimmune inner ear disease (AIED), (population) what impact do disease-modifying antirheumatic agents (DMARDs) (intervention) when compared with no treatment or corticosteroids (comparison) have on auditory and vestibular outcomes (outcome)? Systematic review and meta-analysis. According to PRISMA guidelines, PubMed, Scopus, CINAHL, and Cochrane Library databases were searched from inception to March 10, 2022. Studies of patients receiving DMARDs for the treatment of AIED were selected for review. Case reports, phase I/II trials, studies of patients with secondary AIED, and studies of AIED patients receiving solely corticosteroids were excluded. Primary outcomes were pure-tone audiometry and speech discrimination scores at baseline and after DMARD treatment. Secondary outcomes were rates of subjective audiovestibular complaints and rates of adverse reactions. No objective vestibular outcomes underwent meta-analysis. Mean differences were calculated using RevMan 5.4. Heterogeneity was assessed with the Q test and I2 statistic. Pooled prevalence rates of audiovestibular symptoms were expressed as a percentage with 95% confidence intervals. Ten studies with a total of 187 patients were included. Treatments included methotrexate, etanercept, azathioprine, anakinra, cyclophosphamide, rituximab, and infliximab. Mean treatment duration was 10.8 ± 22.2 months and mean follow-up was 13.7 ± 8.1 months. The pure-tone audiometry and speech discrimination scores mean differences between baseline and post-DMARD were -2.1 [-4.1, -0.1] dB and 13.9 [8.5, 19.4] %, respectively. Seven studies reported 38 adverse events, four of which were classified as serious. DMARDs showed statistically significant improvement in auditory outcomes, as well as subjective symptoms, with relatively low rates of adverse events. They warrant further exploration to better compare with corticosteroids.

Comparative Risk of Alzheimer Disease and Related Dementia Among Medicare Beneficiaries With Rheumatoid Arthritis Treated With Targeted Disease-Modifying Antirheumatic Agents

Cytokine signaling, including tumor necrosis factor (TNF) and interleukin (IL)-6, through the Janus-kinase (JAK)-signal transducer and activator of transcription pathway, was hypothesized to attenuate the risk of Alzheimer disease and related dementia (ADRD) in the Drug Repurposing for Effective Alzheimer Medicines (DREAM) initiative based on multiomics phenotyping. To evaluate the association between treatment with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept and risk of incident ADRD. This cohort study was conducted among US Medicare fee-for-service patients with rheumatoid arthritis aged 65 years and older from 2007 to 2017. Patients were categorized into 3 cohorts based on initiation of tofacitinib (a JAK inhibitor), tocilizumab (an IL-6 inhibitor), or TNF inhibitors compared with a common comparator abatacept (a T-cell activation inhibitor). Analyses were conducted from August 2020 to August 2021. The main outcome was onset of ADRD based on diagnosis codes evaluated in 4 alternative analysis schemes: (1) an as-treated follow-up approach, (2) an as-started follow-up approach incorporating a 6-month induction period, (3) incorporating a 6-month symptom to diagnosis period to account for misclassification of ADRD onset, and (4) identifying ADRD through symptomatic prescriptions and diagnosis codes. Hazard ratios (HRs) with 95% CIs were calculated from Cox proportional hazard regression after adjustment for 79 preexposure characteristics through propensity score matching. After 1:1 propensity score matching to patients using abatacept, a total of 22 569 propensity score-matched patient pairs, including 4224 tofacitinib pairs (mean [SD] age 72.19 [5.65] years; 6945 [82.2%] women), 6369 tocilizumab pairs (mean [SD] age 72.01 [5.46] years; 10 105 [79.4%] women), and 11 976 TNF inhibitor pairs (mean [SD] age 72.67 [5.91] years; 19 710 [82.3%] women), were assessed. Incidence rates of ADRD varied from 2 to 18 per 1000 person-years across analyses schemes. There were no statistically significant associations of ADRD with tofacitinib (analysis 1: HR, 0.90 [95% CI, 0.55-1.51]; analysis 2: HR, 0.78 [95% CI, 0.53-1.13]; analysis 3: HR, 1.29 [95% CI, 0.72-2.33]; analysis 4: HR, 0.50 [95% CI, 0.21-1.20]), tocilizumab (analysis 1: HR, 0.82 [95% CI, 0.55-1.21]; analysis 2: HR, 1.05 [95% CI, 0.81-1.35]; analysis 3: HR, 1.21 [95% CI, 0.75-1.96]; analysis 4: HR, 0.78 [95% CI, 0.44-1.39]), or TNF inhibitors (analysis 1: HR, 0.93 [95% CI, 0.72-1.20]; analysis 2: HR, 1.02 [95% CI, 0.86-1.20]; analysis 3: HR, 1.13 [95% CI, 0.86-1.48]; analysis 4: 0.90 [95% CI, 0.60-1.37]) compared with abatacept. Results from prespecified subgroup analysis by age, sex, and baseline cardiovascular disease were consistent except in patients with cardiovascular disease, for whom there was a potentially lower risk of ADRD with TNF inhibitors vs abatacept, but only in analyses 2 and 4 (analysis 1: HR, 0.76 [95% CI, 0.50-1.16]; analysis 2: HR, 0.74 [95% CI, 0.56-0.99]; analysis 3: HR, 1.03 [95% CI, 0.65-1.61]; analysis 4: HR, 0.45 [95% CI, 0.21-0.98]). This cohort study did not find any association of risk of ADRD in patients treated with tofacitinib, tocilizumab, or TNF inhibitors compared with abatacept.

Medication-induced Pulmonary Injury: A Scenario- and Pattern-based Approach to a Perplexing Problem.

Medication-induced pulmonary injury (MIPI) is a complex medical condition that has become increasingly common yet remains stubbornly difficult to diagnose. Diagnosis can be aided by combining knowledge of the most common imaging patterns caused by MIPI with awareness of which medications a patient may be exposed to in specific clinical settings. The authors describe six imaging patterns commonly associated with MIPI: sarcoidosis-like, diffuse ground-glass opacities, organizing pneumonia, centrilobular ground-glass nodules, linear-septal, and fibrotic. Subsequently, the occurrence of these patterns is discussed in the context of five different clinical scenarios and the medications and medication classes typically used in those scenarios. These scenarios and medication classes include the rheumatology or gastrointestinal clinic (disease-modifying antirheumatic agents), cardiology clinic (antiarrhythmics), hematology clinic (cytotoxic agents, tyrosine kinase inhibitors, retinoids), oncology clinic (immune modulators, tyrosine kinase inhibitors, monoclonal antibodies), and inpatient service (antibiotics, blood products). Additionally, the article draws comparisons between the appearance of MIPI and the alternative causes of lung disease typically seen in those clinical scenarios (eg, connective tissue disease-related interstitial lung disease in the rheumatology clinic and hydrostatic pulmonary edema in the cardiology clinic). Familiarity with the most common imaging patterns associated with frequently administered medications can help insert MIPI into the differential diagnosis of acquired lung disease in these scenarios. However, confident diagnosis is often thwarted by absence of specific diagnostic tests for MIPI. Instead, a working diagnosis typically relies on multidisciplinary consensus. ©RSNA, 2021.

Elicitation of Rheumatologist Preferences for the Treatment of Patients with Rheumatoid Arthritis After the Failure of a First Conventional Synthetic Disease-Modifying Anti-Rheumatic Agent.

IntroductionRheumatoid arthritis (RA) clinical guidelines do not provide strong recommendations for the choice of disease-modifying anti-rheumatic drugs (DMARD) in patients with an inadequate response to methotrexate (MTX), and only limited evidence is available on factors influencing rheumatologist treatment decisions. We aimed to describe therapeutic preferences after the failure of a first-line strategy of MTX in simulated cases of patients with RA.MethodsFictional but realistic case-vignettes (n = 64) of patients with RA and an inadequate response to MTX were developed with a combination of RA-poor prognostic factors and comorbidities. Physicians were presented with eight vignettes and chose the most and least appropriate therapeutic option from the following six options randomly proposed 3 by 3: (1) replacing MTX with another csDMARD; (2) combining MTX with one or more csDMARDs; (3) adding a bDMARD of either TNF inhibitors (TNFi), tocilizumab (TCZ), abatacept (ABA), or rituximab (RTZ). A total of 1605 complete case vignettes were produced and randomly assigned to a representative sample of French rheumatologists. For each vignette, whenever a treatment was preferred, one point was incremented for this treatment; if this treatment was the least desired, one point was removed. Preferences were elicited using a normalized best–worst score.ResultsTwo hundred and four French rheumatologists participated in the study with each vignette being assessed 20–28 times for a completion rate of 94%. TNFi was the first-choice strategy (80% of vignettes), except in cases with a history of infection and pulmonary comorbidity, where ABA was the first preference (85%). TCZ came third in 83% of the cases. Other options were never preferred and repeatedly yielded negative scores.ConclusionsWe observed a conservative trend with TNFi as the main therapeutic choice for patients with RA and inadequate response to MTX. Preference for bDMARD-based strategies increased with the number of RA-poor prognosis factors, whereas an increase in the number of comorbidities resulted in an increased preference for ABA. Understanding clinical decision-making will be particularly important as the therapeutic landscape for RA continues to evolve.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00311-1.

Non-steroidal treatment of cardiac sarcoidosis: A systematic review.

The treatment of active cardiac sarcoidosis (CS) usually involves immunosuppressive therapy, with the goal of preventing inflammation-induced scar formation. In most cases, steroids remain the first-line treatment for CS. However, given the side effect profile of their long-term use, steroid-sparing therapies are increasingly used. There are no published randomized trials of steroid-sparing agents in CS. We sought to do a systematic review to evaluate the current published data on the use of non-steroidal treatments in the management of CS. We searched the Cochrane Library, Ovid Medline, Ovid Embase, PubMed, and Web of Science Core Collection databases from inception of database to August 2020 to identify the effectiveness of biological or synthetic disease-modifying antirheumatic agents (s- and bDMARDs). Secondary objectives include safety profile as well as the change in the average corticosteroid dose after treatment initiation. Twenty-three studies were ultimately selected for inclusion which included a total of 480 cases of CS treated with a range of both s- and bDMARDs. In all included studies, sDMARDs and bDMARDs were studied in combination with steroids or as second or higher-line treatments after therapeutic failure or intolerance to corticosteroid use. Methotrexate (MTX) and infliximab (IFX) were the most common synthetic and biologic DMARDs studied respectively, reported in about 35% of the studies reviewed. The use of steroid-sparing agents was associated with a reduction in the maintenance steroid dose used. In conclusion, steroids will remain as the cornerstone of anti-inflammatory management in patients with CS until trials on the use and safety profile of other immunosuppressive agents are completed and published.

Impact of rheumatoid arthritis and biologic and targeted synthetic disease modifying antirheumatic agents on cancer risk and recurrence.

Several new therapeutic drugs are now available for the management of rheumatoid arthritis (RA). Given that RA has been associated with an increased risk of certain cancers like lymphoma and lung cancer, concern remains about the safety of (newer) immunosuppressants used in RA management as it relates to the risk of cancer. Most meta-analyses of randomized clinical trials of tumor necrosis factor inhibitors (TNFi) have not observed an association between TNFi and risk of incident cancer. Studies of non-TNFi biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs and cancer are also reassuring but limited and of short-term follow-up. Regarding the use of DMARDs in patients with RA and a prior malignancy, retrospective studies have shown that TNFi use is not associated with recurrence. There is a need for ongoing studies on the safety of non-TNFi bDMARDs and targeted synthetic disease modifying anti-rheumatic drugs and recurrent cancer. Further research is also needed to guide the patients, rheumatologists, and oncologists regarding the safest DMARDs to choose for patients with RA and a recent diagnosis of cancer.

Canakinumab injection for the treatment of active Still’s disease, including adult-onset Still’s disease

ABSTRACT Introduction Still’s disease is a systemic, non-monogenic autoinflammatory condition affecting both children and adolescents (systemic juvenile idiopathic arthritis, sJIA) and adults (adult-onset Still’s disease, AOSD). Its clinical spectrum ranges from mild forms to life-threatening cases. Glucocorticoids represent the first-line therapy, but their chronic use is burdened with significant side effects. Hence, add-on therapy with disease modifying anti-rheumatic drugs and biologic anti-cytokine agents is frequently required, especially in patients with severe and recalcitrant clinical phenotypes. Among the targetable cytokines with a primary role in the pathogenesis of Still’s disease, interleukin-1 has a leading position. Areas covered This review presents the available controlled evidence and observational studies regarding the efficacy and safety of canakinumab, a monoclonal antibody targeting interleukin-1β, in the treatment of Still’s disease. Expert opinion Controlled studies fully support the clinical efficacy of canakinumab in the treatment of patients affected by sJIA. Conversely, strong evidences are still lacking in AOSD patients; nevertheless, its use in the adult population is legitimated by an increasing number of cases series and case reports and by preclinical data linking the pathogenesis of these two diseases. In addition, canakinumab has an excellent safety profile. Its role in preventing and treating macrophage activation syndrome is still debated.

Evaluation of Liver Function and Lipid profiles in Iraqi patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with a destructive pattern that affects the joints. It affects the synovial lining tissue of the joints. Females develop rheumatoid arthritis at a higher risk than males. The main treatment for rheumatoid arthritis is disease-modifying anti-rheumatic agents (DMARD) such as methotrexate (MTX) and Etanercept. In this study, ESR, CRP, liver function enzymes, renal function tests and lipid profile were evaluated for rheumatoid arthritis patients. The study includes 120 female patients with rheumatoid arthritis and 60 healthy individuals as a control group with an age range between (20-60) years. The obtained results indicated a significant increase in ESR, CRP activity (p <0.01) in patients compared to the control values. The results also indicated a substantial increase in liver enzymes activity, renal function and lipid profile parameters in rheumatoid arthritis compared to the control values. In conclusion, it appears that DMARD treatment such as methotrexate may be the cause of many complications such as renal impairment. On this basis, we can suggest lowering the weekly dose of methotrexate to patients when effects on liver enzymes activity, renal function, lipid profiles and/or changing treatment when MTX is no longer beneficial.

Apremilast and its role in psoriatic arthritis

Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis often observed in patients with skin psoriasis. Treatment of PsA, especially peripheral PsA, has typically relied on disease-modifying anti-rheumatic agents (DMARDs); however, these agents have limited efficacy and considerable associated toxicity. More recently, monoclonal antibodies (biologic agents) have revolutionized management of immune-mediated diseases; however, these therapies carry a high cost and require parenteral administration. Apremilast, a novel oral DMARD, was approved by the European Union for psoriatic arthritis in 2015. Apremilast inhibits the function of phosphodiesterase-4, a regulator of cyclic adenosine monophosphate, leading to a broad inhibition of proinflammatory mediators and subsequent reduction in tumour necrosis factor-alpha (TNF-α) response. The PALACE and ACTIVE trials, phase III randomized controlled trials for apremilast, showed that apremilast is effective at improving various clinical and patient-reported outcome measures for psoriatic arthritis in both DMARD-naïve and DMARD-experienced PsA patients. Efficacy was limited in patients with previous biologic DMARD failure and the overall efficacy of apremilast appears to be less than biologics agents, though no head-to-head trials exist comparing apremilast to biologic DMARDs. Apremilast is generally well tolerated, with short-lived gastrointestinal side effects being the most commonly reported adverse events. Guidelines suggest a trial of apremilast in patients who have failed traditional oral DMARDs and for whom, biologics are contraindicated. More studies directly comparing apremilast to conventional DMARDs and biologic DMARDs are needed and will be crucial in informing clinical and economic decisions about apremilast role in management of PsA.

Certain perspectives about the use of corticosteroids for managing hospitalized patients with rheumatic diseases.

The administration of cortisone to a bedridden patient with rheumatoid arthritis (RA) 70years ago was a transformative event in modern medicine. We have since struggled to balance the near-miraculous anti-rheumatic with the yet all-too-frequent devastating side effects of glucocorticoids (GC). With the current availability of newer disease-modifying and biologic anti-rheumatic agents, we were rather surprised to note that 94% of sick hospitalized patients with systemic rheumatic diseases at our medical center were on corticosteroids during a 3-month observation period. Comparing contemporary with past practices from historical references, we confirmed a perhaps paradoxical trend of increasing steroid usage in certain contexts over the years. Sixty-seven percent of our hospitalized lupus patients were started on GC of greater than 30mg prednisone equivalent compared with 50% in the 1950s. Seventy-five percent of our RA inpatients had their GC dose increased on discharge. Both (2/2) our new RA patients were started on GC, compared with 69% in the 2000s and just 36% in the 1990s. This likely reflects both improved abilities to keep sick patients alive and inability of other anti-rheumatic therapies to consistently induce or sustain disease remission compared with the usually highly efficacious yet inexpensive GC in these particular patients. Administration of glucocorticoids to ill, often infected, patients with systemic rheumatic diseases remains more art than science. Current perspectives view glucocorticoids as considerably less salutary than previously thought; we are still challenged to keep our patients from developing preventable complications. These observations emphasize the need for more and better therapeutic alternatives to glucocorticoids. There are now several examples-disease-modifying and biologic medications for RA and biologics for lupus and vasculitis-that suggest the possibility of caring for our patients without the historical reliance on corticosteroids. We have made enormous progress since steroids were first offered to a patient with RA in 1948. We are hopeful the future will bring us interventions of comparable or better efficacy that are safer.

P38 A rare case of rheumatoid arthritis with perforating collagenosis

Abstract Background Rheumatoid arthritis has multiple cutaneous manifestations with rheumatoid nodule being the commonest one. A maculopapular rash in setting of rheumatoid arthritis has a varied list of differentials including rheumatoid vasculitis, pyoderma gangrenosum, rheumatoid neutrophilic dermatosis, interstitial granulomatous dermatitis and palisaded neutrophilic granulomatous dermatitis. We present a rare case of patient with rheumatoid arthritis with perforating collagenosis. Methods A case report is presented in the results section. Results A 64 year old lady known to have seropositive rheumatoid arthritis for the past 6 years with poor compliance to treatment presented with maculopapular lesions on both her legs and abdomen. The lesions were itchy in nature and later became ulcerative. The lesions spread to various parts of the body over the next 4 weeks and patient was seen by a dermatologist who initially prescribed topical therapy and the patient came off her disease modifying anti rheumatic agents. She underwent a skin biopsy as initial investigations were otherwise unremarkable. Skin biopsy revealed a diagnosis of perforating collagenosis. She was given topical steroids and counselled regarding the need to take her disease modifying anti rheumatic drugs regularly. There was 95% resolution of skin lesions within 6 months. Conclusion Perforating collagenosis is a skin disorder characterised by transepithelial expulsion of dermal tissue which presents as a papulonodular rash with central keratin plugs. It is usually associated with diabetes mellitus and chronic kidney disease but rarely been reported in association with rheumatoid arthritis. Literature review revealed that there have been only 2 cases reported previously. The first case has been described in 2010 in a man from Singapore on treatment for RA for 2 years. Second case has been described by Ikeda et al in 2019 in a case of rheumatoid vasculitis. Clinically it presents as umbilicated, hyperkeratotic papules with a central white keratotic crust. Koebnerization may be seen and itching of surrounding regions may lead to papules to coalesce and form plaques. A biopsy will reveal features similar to those seen in the primary disease where perforating collagenosis shows cup shaped invagination of the epidermis filled with a plug consisting of keratin and cellular debris. There have been no trials and treatment is based on case reports. We believe that better compliance to her disease modifying anti rheumatic agent therapy, leading to improved treatment of the systemic cause had a significant role in resolving her skin lesions. Disclosures S. Deb None. S. Srirangan None.

The Utility of Radiographic Focal Erosions of Hands or Feet in Predicting DXA-defined Osteoporosis of the Hip in Patients with Rheumatoid Arthritis.

Osteoporosis is a common comorbidity in Rheumatoid Arthritis (RA) patients and can result in estimated double risk of pathological fractures. Bone Mineral Density (BMD) is known to decrease with RA because of mechanisms incorporating traditional as well as disease-specific causes. With the advent of newer disease-modifying antirheumatic agents and bone protection medications, it is becoming important to identify those individuals who are at increased risk of developing osteoporosis among RA patients. In the current study, we aim to evaluate a multitude of factors including focal erosions on radiographs of hands or feet that can predict osteoporosis in RA patients. After obtaining IRB approval, 26 patients (20 females & 6 males) with a median age of 62 years (95% CI: 57.4 - 66.0) were retrospectively identified from a Rheumatology clinic database with an established diagnosis of RA but not taking osteoporosis medications. A detailed assessment was accomplished including evaluating a number of disease-specific variables, hands/feet radiographs and Dual-energy X-ray Absorptiometry (DXA). The total hip BMD was lower in RA patients with radiographic erosions (0.862 g/cm2 ± 0.17) compared to those patients without erosions (1.011 g/cm2 ± 0.13). On univariate logistic regression, the presence of radiographic erosions predicted osteoporosis of the hip (p = 0.04). ROC curve demonstrated satisfactory performance of erosions in predicting WHO-defined osteoporosis or osteopenia at the hip (AUC = 0.732). RA patients who show radiographic erosions are more likely to develop hip osteoporosis that may require further intervention.

The Current State of Pediatric Health Care: Changes and Challenges.

1. Shabana Yusuf, MD* 2. Lynn Garfunkel, MD* 3. Catherine Forster, MD† 4. Janet R. Serwint, MD‡ 1. *Editorial Board Member, 2. †Editorial Fellow, and 3. ‡Associate Editor, In Brief, Pediatrics in Review > Over the years, women have prominently advanced pediatrics. Very few women were members of the original editorial board of Pediatrics in Review . That has since changed. Four prominent women on our current editorial board offer their thoughts on the current state and possible future of pediatrics. > > —JZ, HDA Although the global mortality rate of children has dropped dramatically (from 36% in 1900 to 12% in 1979 to <4% in 2017), with most children today living into adulthood, there remain significant racial, ethnic, and geographic differences. Diseases have evolved and provider perspectives have changed. Medical advances in 3 areas of pediatric care—prevention, diagnosis, and treatment—have led to substantial changes in child health. Vaccine-preventable diseases have declined remarkably. In 1977, a nationwide immunization program was established to increase vaccination rates to 90%. With development of the Haemophilus influenzae and pneumococcal vaccines, bacterial meningitis and its complications are rare, although bacterial pneumonia and otitis media still occur. More recently, vaccine refusal has increased the rates of unvaccinated children (from 0.3% in 2001 to 1.3% in 2017), causing unnecessary local epidemics and increased physician time for counseling parents. Human immunodeficiency virus infection rapidly increased in the 1980s, and peaked at epidemic proportions in …

Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial

Antiretroviral therapy (ART) is typically composed of a combination of three antiretroviral drugs and is the treatment of choice for people with human immunodeficiency virus type 1/acquired immune deficiency syndrome (HIV-1/AIDS). However, it is unable to impact on viral reservoirs, which harbour latent HIV-1 genomes that are able to reignite the infection upon treatment suspension. The aim of this study was to provide an estimate of the safety of the disease-modifying antirheumatic agent auranofin and its impact on the HIV-1 reservoir in humans under intensified ART. For this purpose, an interim analysis was conducted of three of the six arms of the NCT02961829 clinical trial (five patients each) with: no intervention, i.e. continuation of first-line ART; intensified ART (ART + dolutegravir and maraviroc); and intensified ART plus auranofin. Auranofin treatment was found to be well tolerated. No major adverse events were detected apart from a transient decrease in CD4+ T-cell counts at Weeks 8 and 12. Auranofin decreased total viral DNA in peripheral blood mononuclear cells compared with ART-only regimens at Week 20 (P = 0.036) and induced a decrease in integrated viral DNA as quantified by Alu PCR. Despite the limited number of patient-derived sequences available in this study, phylogenetic analyses of nef sequences support the idea that auranofin may impact on the viral reservoir. [ClinicalTrials.gov ID: NCT02961829].

Management of asymptomatic coccidioidomycosis in patients with rheumatic diseases.

Coccidioidomycosis is an endemic fungal infection common in the southwestern United States. Some rheumatology clinics periodically screen patients with coccidioidal serology, resulting in the identification of patients who are serologically positive but without clinical symptoms. The management of such patients is unclear. A retrospective study was conducted between 2007 and 2015 at two arthritis centers in Tucson, Arizona. The asymptomatic patients were identified who were receiving disease-modifying antirheumatic agents and had a positive coccidioidal serology. Serological testing including IgM and IgG was performed by enzyme immunoassay (EIA), immunodiffusion (IDTP and IDCF), or complement fixation. Out of 71 patients who were identified with positive coccidioidal serologies, 19 were asymptomatic. 18/19 patients continued antirheumatic therapy, 13 without interruption. 13/19 patients received no antifungal treatment, including 10 who remained on antirheumatic treatment. The other six were started on fluconazole, ranging from 8 to 73months (median 30.5months). After a median follow-up of 43months, no patient developed clinically active coccidioidomycosis. Overall, 14 had only a positive EIA serological test. These results suggest that continued antirheumatic therapy is safe in asymptomatic patients with positive coccidioidal serological tests and that routine implementation of antifungal treatment may not always be warranted. The findings also raise concern regarding the utility of routine serological testing of asymptomatic patients residing in the coccidioidal endemic area, mainly using the EIA test.