Non-biologic DMARDs Research Articles

SAT0150 CHANGES IN PATIENT-REPORTED OUTCOME (PRO) SCORES FOR NAUSEA AND FATIGUE FOLLOWING WEEKLY METHOTREXATE DOSE IN A REAL-WORLD SAMPLE OF RA AND PSA PATIENTS IN THE ARTHRITISPOWER REGISTRY

Background:Methotrexate (MTX) is frequently used in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) because of its beneficial effects in both populations1-3. Despite the well-known benefits of MTX, it is associated with a number of potential side effects4-6These include nausea and fatigue, are often temporally related to the timing of weekly MTX administration, and can be severe. The combined patient-reported side effects, along with potential of long-term toxicity, may make use of MTX more burdensome. Currently, there is a gap in patient-centered studies that focus on patients’ experience with MTX.Objectives:Examine patient temporal experience of fatigue and nausea relating to oral MTX therapy for the treatment of RA and PsA.Methods:Adult US patients in the ArthritisPower registry with self-reported RA or PsA taking MTX for less than 10 years were invited to participate in the study via email invitation. Participants (pts) completed a screener and brief online survey. In an ancillary study to the ArthritisPower registry and using a self-controlled case series study design where pts serve as their own control to avoid between-person confounding, pts were asked to complete a set of up to 8 assessments within 6-36 hours (‘risk’) and 96-144 hours (‘control’) after taking their oral dose of MTX each week, for up to 4 weeks. Risk and control windows were selected based on the expected temporal relationship between MTX use and peak onset of these symptoms. Assessments included PROMIS short forms for same-day Fatigue, same-day Nausea/Vomiting, and Patient Global. Descriptive statistics were conducted using paired t-tests two-way comparisons. Within-person change in PROMIS scores between the risk (1-2 days after MTX) and control (4-6 days after MTX) windows were analyzed using mixed models for repeated measures, stratified on whether pts reported fatigue or nausea with MTX at baseline. Recruitment for this study is ongoing.Results:As of December 2019, 91 pts had participated, of whom 76.9% were living with RA and 28.6% with PsA, with mean baseline PROMIS Patient Global score (SD) of 39.5 (7.1). Mean age (SD) was 50.9 (12.0) years, 84.6% female, 92.3% White, with mean BMI 33.7 (8.8). Mean duration of MTX treatment among current users was 2.1 (2.8) years. Among pts, 41.8% were on a biologic DMARD and 58.2% on non-biologic DMARDs only. Among pts reporting baseline nausea (n=30, 33.0%) where paired within-week measures were observed (n=64 observations among 20 pts), the mean increase in the PROMIS Nausea score was 4.5 units (adjusted p=0.003). Among those reporting MTX-associated fatigue (n=39, 42.9%) as a side effect of MTX on their baseline survey where paired within-week measures were observed (n=96 observations among 28 pts), the mean increase in PROMIS Fatigue was 4.7 (adjusted p=0.004) units. In those pts, the proportion of pts with worsened nausea and fatigue with minimally important difference of >5 units7-8was 40.0% (nausea), and 60.7% (fatigue) [Figures 1 and 2].Conclusion:People taking MTX to manage RA or PsA commonly experience bothersome side effects, notably fatigue and nausea, that are temporally related to weekly MTX dosing. In this sample, one-third or more of pts were bothered by nausea or fatigue shortly after MTX dosing, many of them with clinically meaningful symptoms.

P262 Guselkumab, an anti-interleukin-23p19 monoclonal antibody, in patients with active PsA who were biologic-naïve or prior TNFα inhibitor-treated: week 24 results of a Phase 3, randomised, double-blind, placebo-controlled study

Abstract Background Guselkumab (GUS), an anti-interleukin-23p19 monoclonal antibody, is approved to treat psoriasis (PsO). We evaluated GUS efficacy and safety in a Phase 3, double-blind, placebo (PBO)-controlled trial in patients with active PsA who were biologic-naïve or prior TNFα inhibitor (TNFi)-treated (DISCOVER-1). Methods Adults with active PsA (≥3 swollen + ≥3 tender joints; CRP ≥0.3mg/dL) despite standard therapies (eg, non-biologic DMARDs, apremilast, or NSAIDs) were eligible. ∼30% of patients previously could have received or have had inadequate response to 1-2 TNFi. Patients were randomised 1:1:1, stratified by Week [W]0 DMARD use and prior TNFi use, to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W (Q8W); or PBO. Concomitant stable use of select non-biologic DMARDs, oral corticosteroids, and NSAIDs was allowed. At W16, patients with <5% improvement in tender+swollen joints could initiate or increase the dose of permitted medications while continuing study treatment. The primary endpoint was ACR20 at W24. Major secondary endpoints included: Investigator’s Global Assessment (IGA) PsO response (IGA=0/1 + ≥2-grade reduction) at W24 in patients with ≥3% BSA PsO and IGA ≥2 at W0; changes in DAS28-CRP, HAQ-DI and SF-36 PCS scores and ACR50/70 response at W24; and ACR20/50 response at W16. As preplanned, enthesitis or dactylitis data were pooled with those from the companion Phase 3 study DISCOVER-2. Due to different regional health authority regulatory requirements, Global and US multiplicity control procedures were prespecified with statistical results from US procedures presented. Unadjusted (nominal) p-values are provided for other endpoints. Adverse events (AEs) through W24 are reported. Results 381 patients were treated and analyzed; baseline characteristics were consistent with moderate-to-severe disease (mean BSA involved with PsO: 13.4%, patients with IGA=3-4: 42.5%; mean swollen/tender joint counts: 9.8/19.3). Significantly more patients receiving GUS Q4W (58.6%) and Q8W (52.8%) vs PBO (22.2%, both p < 0.001) achieved ACR20 response at W24. Consistent response rates were observed in the subgroups of patients with or without prior TNFi use. Significantly greater improvements in HAQ-DI and SF-36 PCS scores were seen in GUS- vs PBO-treated patients from W0 to W24. Among 249 patients with ≥3% BSA PsO and IGA ≥2 at W0, significantly more GUS- vs PBO-treated patients achieved IGA response. Higher proportions of patients achieved ACR20 response at W16, ACR50 response at W16/24, ACR70 response at W24, and PASI75/90/100 responses at W24. More GUS Q4W- or Q8W- vs PBO-treated patients achieved MDA response at W24. Serious AEs, serious infections, and death occurred in 9/381 (2.4%), 2/381 (0.5%), and 1/381 (0.3%) patients, respectively. Conclusion In patients with active PsA who were biologic-naïve or had been treated with TNFi, both GUS Q4W and Q8W demonstrated efficacy for joint and skin symptoms, physical function, and quality of life relative to PBO. Observed AEs were consistent with GUS safety established in PsO. Disclosures A. Deodhar: Other; A.D. has been a study investigator for Janssen clinical trials. P. Helliwell: Other; P.H. has been a research investigator for Janssen. W. Boehncke: Other; W.B. has been a study investigator for Janssen. E.C. Hsia: Other; E.H. is a Janssen employee. A.P. Kollmeier: Other; A.K. is a Janssen employee. R.A. Subramanian: Other; R.S. is a Janssen employee. X.L. Xu: Other; X.X. is a Janssen employee. S. Sheng: Other; S.S. is a Janssen employee. B. Zhou: Other; B.Z. is a Janssen employee. P.C. Gorecki: Other; P.G. is a Janssen employee. C. Ritchlin: Other; C.R. has been a study investigator for Janssen.

The Management of Perioperative Immunosuppressant Medications for Rheumatoid Arthritis During Elective Hand Surgery

Rheumatoid arthritis (RA) is a destructive inflammatory disease that commonly involves joints of the hand and wrist. Different recommendations exist for continuing or discontinuing immunosuppressant medications during the perioperative time period. The purpose of our study was to determine whether continuing or discontinuing medications (steroids, nonbiological, and/or biological disease-modifying antirheumatic drugs [DMARDs]) were associated with an increased or decreased risk of postoperative complications. We performed a single-center, retrospective review of a cohort of RA patients who had elective hand surgery by a single surgeon. Patients were included if they had a documented diagnosis of seropositive RA by a rheumatologist and had elective hand surgery and/or a disease-related surgical procedure involving the upper extremity between January 2008 and August 2018. We stratified patients into different groups for comparison by classes of immunosuppressant medications for managing RA. These classes included corticosteroids, nonbiological DMARDs, biological DMARDs, and/or no medications. Immunosuppressant medications were then compared with no medications for the incidence of postoperative overall complications. Eighty-eight patients had elective hand and/or upper extremity surgeries for RA. Mean patient age at the time of surgery (± SD) was 55 ± 13 years (range, 24-74 years). Of these 88 patients, 8 (9%) overall complications occurred. Complications were wound healing failures (n= 5), tendon rupture (n= 1), hematoma (n= 1), and surgical-site infection (n= 1). Perioperative medications included steroids (n= 31), nonbiological DMARDs (n= 68), biological DMARDs (n= 5), and no medication (n= 27). There were no significant differences in overall complications between patients on immunosuppressant medications and those on no medications. Median (interquartile range) follow-up was 11.5 months (5-25.8) (range, 2-74 months). We found that patients who continued or discontinued medications within 1 dosing interval of their usual dose perioperatively had similar rates of complications following elective hand surgery. Therapeutic IV.

Oral corticosteroid use during pregnancy and risk of preterm birth.

To evaluate the associations between oral corticosteroid (OCS) dose early and late in pregnancy and preterm birth (PTB) among women with RA. Pregnant women in the MotherToBaby Pregnancy Studies (2003-2014) with RA (n = 528) were included in the primary analysis. Information was collected by phone interview and from medical records. We estimated risk ratios (RR) for OCS dose trajectories and other disease-related medications before gestational day 140 and hazard ratios (HR) for time-varying exposures after gestational day 139. PTB risk was 15.5% overall. Compared with no OCS, PTB risk was increased in high (adjusted (a)RR: 4.77 (95% CI: 2.76, 8.26)) and medium (aRR: 1.81 (95% CI: 1.10, 2.97)) cumulative OCS dose trajectories during the first 139 gestational days. The low cumulative trajectory group was associated with an increased risk of PTB that was not statistically significant (aRR: 1.38 (95% CI: 0.79, 2.38)), and DMARDs were not associated with PTB (biologic DMARDs aHR: 1.08 (95% CI: 0.70, 1.66); non-biologic DMARDs aHR: 0.87 (95% CI: 0.55, 1.38)). OCS exposure to ⩾10 mg of prednisone equivalent daily dose after gestational day 139 vs none was associated with increased PTB rate (aHR: 2.45 (95% CI: 1.32, 4.56)), whereas <10 mg was associated with a modestly increased rate of PTB that was not statistically significant (aHR: 1.18 (95% CI: 0.60, 2.30)). Higher OCS doses vs no OCS use, both earlier and later in pregnancy, were associated with an increase in PTB among women with RA.

Trends in diagnostic prevalence and treatment patterns of male and female ankylosing spondylitis patients in the United States, 2006\u20132016

BackgroundThere has been much variation between epidemiological studies that report the prevalence of ankylosing spondylitis (AS). This study aimed to analyze the diagnostic prevalence rates and treatment patterns of male and female AS patients in the United States adult insured population from 2006 to 2016.MethodsTrends in AS prevalence were calculated for the 11-year period covering January 1, 2006 to December 31, 2016. Adult (18+ years old) AS patients were included in this retrospective analysis of medical and pharmacy claims data from the IBM Marketscan Commercial, Medicaid and Medicare-Supplemental Claims database. Prevalence was determined as having ≥1 AS diagnostic codes (ICD-9:720.0; ICD-10:M45.x). Trends in treatment patterns were also analyzed and stratified by gender.ResultsThe AS prevalence increased from 0.04 to 0.09% from 2006 to 2016. The mean age between 2006 and 2016 ranged from 49.52–50.00 years. In 2006, approximately 40% of AS patients were female, while in 2016 over 47% of AS patients were female. Rates of use of TNF inhibitors and oral glucocorticoids increased, while NSAIDs and non-biologic DMARDs (sulfasalazine & methotrexate) rates decreased. Opioid use rates were stable. In 2016, males were more likely to be prescribed biologics, while females were more likely to be prescribed methotrexate, sulfasalazine, NSAIDs, muscle relaxants, anticonvulsants, opioids, and glucocorticoids.ConclusionsThe prevalence of AS diagnosis codes more than doubled between 2006 and 2016, but the very low prevalence suggests that AS continues to be underdiagnosed and under-addressed in routine clinical practice. Despite the increase in female AS patients, females were less likely to be prescribed biologics compared to male AS patients.

The Use of Tocilizumab in Combination with Methotrexate in Indonesian Rheumatoid Arthritis Patients (PICTURE INA Study)

Background Aim of this research is to assess the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) in Indonesian patients with moderate to severe active rheumatoid arthritis (RA) who have an inadequate response to non-biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in  Indonesian male or female patients aged ≥ 18 years old, with a diagnosis of RA for &gt; 6 months based on ACR 1987 revised criteria with moderate to severe disease activity (DAS28 score &gt; 3.2) after ≥ 12 weeks of non-biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous (IV), every 4 weeks for a total of 6 infusion in combination with oral MTX (10−25 mg) every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state (DAS28 &lt; 3.2), percentage of patients achieving reduction &gt; 1.2 point of DAS28, percentage of patients achieving remission (DAS28 &lt; 2.6), and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100% patients reached low disease activity (DAS28 ≤ 3.2) at last study visit (week 24) and clinically significant improvement (reduction at least 1.2 units) at every visit in DAS28, both for ITT or PP patients. Remission (DAS28 &lt; 2.6) was observed in 82.1% (ITT patients) and 93.1 % (PP patients) on last study visit. ACR20, ACR50, and ACR70 were achieved in 20%, 34%, and 34% (ITT patients), and 7%, 24%, and 62% (PP patients) on week 24. There were 3 out of 39 patients (7.69%) with adverse events (AE) and serious adverse events (SAE) that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction (30.7%), hypercholesterolemia (23.1%), followed by arthralgia (20.5%) Twelve percent of patients needed dose modification due to elevated liver enzyme (elevated ALT/SGPT level).Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non- biologic DMARD nonresponsive RA patients of PICTURE INA study.   Keywords: Rheumatoid Arthritis, Tocilizumab, DMARD, DAS28

The Use of Tocilizumab in Combination with Methotrexate in Indonesian Rheumatoid Arthritis Patients (PICTURE INA Study)

Background Aim of this research is to assess the efficacy and safety of tocilizumab (TCZ) in combination with methotrexate (MTX) in Indonesian patients with moderate to severe active rheumatoid arthritis (RA) who have an inadequate response to non-biologic DMARDs.Methods This was a interventional, prospective, single arm, multicenter, study in Indonesian male or female patients aged ≥ 18 years old, with a diagnosis of RA for &gt; 6 months based on ACR 1987 revised criteria with moderate to severe disease activity (DAS28 score &gt; 3.2) after ≥ 12 weeks of non-biologic DMARDs treatment. The treatment consisted of tocilizumab, 8 mg/kg, intravenous (IV), every 4 weeks for a total of 6 infusion in combination with oral MTX (10−25 mg) every week. Efficacy was assessed based on the percentage of patients achieving low disease activity state (DAS28 &lt; 3.2), percentage of patients achieving reduction &gt; 1.2 point of DAS28, percentage of patients achieving remission (DAS28 &lt; 2.6), and percentage of patients with ACR20, ACR50, and ACR70 responses. Descriptive statistics will be used for presentation of results.Results 100% patients reached low disease activity (DAS28 ≤ 3.2) at last study visit (week 24) and clinically significant improvement (reduction at least 1.2 units) at every visit in DAS28, both for ITT or PP patients. Remission (DAS28 &lt; 2.6) was observed in 82.1% (ITT patients) and 93.1 % (PP patients) on last study visit. ACR20, ACR50, and ACR70 were achieved in 20%, 34%, and 34% (ITT patients), and 7%, 24%, and 62% (PP patients) on week 24. There were 3 out of 39 patients (7.69%) with adverse events (AE) and serious adverse events (SAE) that resulted in discontinuation of TCZ treatment, consisting of 1 patient with SAE of sepsis ec acquired community pneumonia, 1 patient with SAE of pneumonia tuberculosis, and 1 patient with AE of candidiasis. Most common adverse events were hepatic dysfunction (30.7%), hypercholesterolemia (23.1%), followed by arthralgia (20.5%) Twelve percent of patients needed dose modification due to elevated liver enzyme (elevated ALT/SGPT level).Conclusion Tocilizumab seems to be efficacious and likely to have good safety profile in non- biologic DMARD nonresponsive RA patients of PICTURE INA study. Keywords: Rheumatoid Arthritis, Tocilizumab, DMARD, DAS28

PMS40 - Cost-Effectiveness of Tofacitinib in Patients with Rheumatoid Arthritis in China

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation and leads to bone destruction and other extra-articular and systemic manifestations. This analysis examined the cost-effectiveness of tofacitinib in patients with RA in China. A previously published lifetime, cohort-based, cost-effectiveness model for patients with rheumatoid arthritis was localized to China. The model evaluated three possible lines of biologic disease-modifying antirheumatic drugs (bDMARDs) therapy plus a final line of palliative care in patients with an inadequate response to non-biologic DMARDs (cDMARD-IR). Included therapeutic options were the following: tofacitinib, YSP (etanercept biosimilar), adalimumab, infliximab, toclizumab, and palliative care (methotrexate and leflunomide). YSP was assumed to have equal effectiveness to etanercept in the base case, and 90% in sensitivity analysis. Response to therapy was evaluated every 6 months through American College of Rheumatology (ACR) criteria (first-line biologic) and Health Assessment Questionnaire Disability Index (HAQ-DI) scores (subsequent lines). HAQ-DI scores were mapped to utility values to calculate QALYs. Drug costs, adverse events (injection-site reactions and severe infections), physician costs, and administration costs were included. Costs were presented in 2017 CNY and from a payer’s perspective. The sequence of tofacitinib, adalimumab, and infliximab dominated (less costly, more effective than) YSP followed by adalimumab, and then toclizumab (incremental costs and QALYs of -¥39,257 and 0.44). Tofacitinib was cost-effective against YSP when both treatments were followed by infliximab (second-line) and toclizumab (third-line) with an ICER of ¥380 (incremental cost and QALYs of ¥172 and 0.45, respectively). Tofacitinib was, again, cost-effective against YSP when both were followed by adalimumab (second-line) and toclizumab (third-line) with an ICER of ¥86,688 (incremental costs and QALYs of ¥58,589 and 0.68, respectively). Sensitivity analysis related to YSP’s effectiveness confirmed the base case results. Tofacitinib is a cost-effective alternative to YSP in patients with rheumatoid arthritis in China.

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity.Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants (1) commencing anti-TNF therapy (n = 10,813), or (2) changing between non-biologic DMARDs (n = 2992), (3) Early Rheumatoid Arthritis Network participants (n = 813), and (4) participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n = 45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation.DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components.DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA.

Systemic lupus erythematosus in a male patient

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a broad spectrum of clinical presentations. Female to male ratio is approximately 9:1.A 20 years old male was admitted to HAM Hospital 3 months ago with chief complaint pain in both knees joint. After anamneses, physical examination and laboratory test the patient was diagnosed with systemic lupus erythematosus. The patient tested positive for ANA and anti-ds-DNA antibody test. The patient was with giving non-biologic DMARDS @myfortic 360mg, methylprednisolone, chloroquine and other symptomatic drugs.

Drug immunogenicity in patients with inflammatory arthritis and secondary failure to tumour necrosis factor inhibitor therapies: the REASON study.

The aims were to evaluate the prevalence of anti-drug antibodies (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF therapy and to correlate ADA presence with anti-TNF concentration and clinical response. This was a cross-sectional, observational study of patients with active RA or SpA experiencing secondary failure to etanercept (ETN), infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were permitted. Serum anti-TNF and ADA levels were measured with two-site ELISA. Among 570 evaluable patients, those with RA (n = 276) were mostly female (80 vs 39%), older (56 vs 48 years), received concomitant DMARDs (83 vs 47%) and had maintained good clinical disease control for longer (202 vs 170 weeks) compared with patients with SpA (n = 294). ADA were found in 114/570 (20.0%) patients; 51/188 (27.1%) against INF and 63/217 (29.0%) against ADL; none against ETN. Of these 114 patients, 92 (81%) had no detectable serum drug concentrations. Proportionately more patients with SpA (31.3%) had anti-INF antibodies than those with RA (21.1%; P = 0.014). A significantly lower proportion of patients receiving concomitant DMARDs (16.5%) developed ADA than those on monotherapy (26.4%; P < 0.05). In patients with RA or SpA and secondary failure, the development of ADA against ADL or INF, but not ETN, appears to be one of the main reasons for secondary treatment failure, but not the only one. Further investigations are needed to determine other causes of anti-TNF failure.

Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condition in Patients with Rheumatoid Arthritis?

Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

Review of Routine Laboratory Monitoring for Patients with Rheumatoid Arthritis Receiving Biologic or Nonbiologic DMARDs.

Safety concerns associated with many drugs indicated for the treatment of rheumatoid arthritis (RA) can be attenuated by the early identification of toxicity through routine laboratory monitoring; however, a comprehensive review of the recommended monitoring guidelines for the different available RA therapies is currently unavailable. The aim of this review is to summarize the current guidelines for laboratory monitoring in patients with RA and to provide an overview of the laboratory abnormality profiles associated with each drug indicated for RA. Recommendations for the frequency of laboratory monitoring of serum lipids, liver transaminases, serum creatinine, neutrophil counts, and platelet counts in patients with RA were compiled from a literature search for published recommendations and guidelines as well as the prescribing information for each drug. Laboratory abnormality profiles for each drug were compiled from the prescribing information for each drug and a literature search including meta-analyses and primary clinical trials data.

Disparities in care by insurance status for individuals with rheumatoid arthritis: analysis of the medical expenditure panel survey, 2006–2009

Objective: Treatment guidelines for rheumatoid arthritis (RA) recommend early, aggressive treatment with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs) to minimize long-term disability. We aimed to assess differences in medical resource utilization, drug therapy, and health outcomes among RA patients by insurance type in the United States.Methods: Individuals with a self-reported diagnosis of RA were identified in the Medical Expenditure Panel Survey (MEPS) database, 2006–2009. Data regarding sociodemographic characteristics, insurance type and status, and outcomes (including health care resource utilization, prescription medication use, health status, and patient-reported barriers to health care) were extracted. Multivariable regression analyses were used to examine the impact of insurance type (private, Medicare, Medicaid, or uninsured) on outcome measures while controlling for age group, sex, and race/ethnicity.Results: A total of 693 individuals with a self-reported diagnosis of RA during the study period were identified; 423 were aged 18–64 years and 270 were aged ≥65 years. Among patients aged 18–64, those with Medicaid or who were uninsured were less likely than those with private insurance to visit a rheumatologist (adjusted odds ratio [aOR] 0.13 and 0.17, respectively; p < .001) and to receive biologic DMARDS (aOR 0.09 [p < .001] and 0.16 [p < .01], respectively); those with Medicaid were also less likely to receive nonbiologic DMARDS (aOR 0.26 [p < .01]). Those with Medicaid were more likely than those with private insurance to be unable/delayed in getting prescription drugs (aOR 2.9 [p < .05]), to experience cognitive, social, and physical limitations (aOR 8.7 [p < .001], 4.7 [p < .001], and 2.5 [p < .05], respectively); they also reported significantly lower general health and health-related quality of life. Patients aged ≥65 experienced greater equity in care and outcomes.Conclusions: Younger RA patients with Medicaid (including those who receive coverage under the Medicaid expansion component of the Affordable Care Act) may be at risk for inadequate treatment.

Meta-analysis of long-term joint structural deterioration in minimally treated patients with rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint structural deterioration. Driven by recent expectations that patients in clinical trials randomized to placebo should be ‘rescued’ with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear. With longer-term evidence of the rate of joint deterioration with minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials. The aim of this study was to estimate radiographic structural deterioration over time in patients with moderate-to-severe RA minimally treated with DMARDs.MethodsA literature review identified evidence of joint structural deterioration in patients with (DMARD-IR population) and without (non-DMARD-IR population) a history of inadequate response to DMARDs. Patients were minimally treated with one non-biologic DMARD or palliative care (non-DMARD-IR population only). Outcomes of interest were the (modified) Total Sharp Score (TSS) and subscales (Erosion Subscore [ES] and Joint Space Narrowing [JSN] Subscore), and Larsen score. Pooled joint-deterioration curves over time were obtained with meta-analysis models.ResultsMean change from baseline in TSS increased in the DMARD-IR population from 1.14 (95 % credible interval [CrI] 0.66, 1.67) to 9.84 (5.68, 14.46) at Weeks 12 and 104, respectively, and a non-linear increase of 1.56 (0.79, 2.34) and 5.13 (−1.35, 11.67) in the non-DMARD-IR population. At the same time points, mean changes (95 % CrI) were 0.51 (0.27, 0.83) and 4.43 (2.38, 7.21) for ES and 0.36 (0.09, 0.67) and 3.14 (0.80, 5.78) for JSN in the DMARD-IR population, whereas corresponding changes in the non-DMARD-IR population were 0.69 (0.31, 1.12) and 2.93 (0.92, 5.02), and 0.29 (0.17, 0.44) and 2.55 (1.45, 3.80), respectively. Larsen scores were only available for the non-DMARD-IR population, with mean changes (95 % CrI) of 0.08 (0.04, 0.11) and 0.65 (0.36, 0.96) at Weeks 12 and 104, respectively.ConclusionMinimal treatment of RA with one non-biologic DMARD results in deterioration of joint structure in patients with or without a history of inadequate response to non-biologic DMARDs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1195-4) contains supplementary material, which is available to authorized users.

Safety of biologic DMARDs in RA patients in real life: A systematic literature review and meta-analyses of biologic registers

ObjectivesIn daily practice, safety in rheumatoid arthritis (RA) patients receiving biological treatment is an important issue. Unlike randomized controlled trials, biologic registers provide long-term real life safety data. To identify all biologic registers worldwide, to extract and analyze data regarding safety in RA patients under biologics. MethodSystematic review was performed independently by 2 rheumatologists using PUBMED, COCHRANE Library and EMBASE databases, up to December 2014. Worldwide biologic registers and related publications were identified. Data on safety issues in RA patients were extracted for meta-analyses. Random-effect meta-analyses were performed to estimate risk ratios (RRs) of mortality, cardiovascular events, cancer, including lymphoma and melanoma and serious infections between (1) biological and non-biological DMARD (cDMARD), (2) between biologics when data were available. ResultsForty-three biological registers were identified worldwide and 27 publications were included for safety meta-analyses on anti-TNFs. Compared to cDMARD, mortality and cardiovascular events were significantly decreased in patients treated with anti-TNFs: RR=0.60 [95% CI 0.38–0.94] and RR=0.62 [0.44–0.88], respectively. Anti-TNFs did not increase the risk of solid cancer in patients without or with prior malignancy (RR=0.84 [0.60–1.18] and RR=0.77 [0.29–2.03], respectively), lymphoma (RR=0.90 [0.62–1.31]) and melanoma (RR=1.17 [0.86–1.59]). As expected, serious infections were significantly increased during anti-TNF treatment (RR=1.48 [1.18–1.85]) compared to cDMARD. No significant difference was found between soluble receptor to TNF and monoclonal antibodies (RR=0.55 [0.22–1.35]). ConclusionsBy reducing dramatically chronic inflammation in RA patients, anti-TNFs decrease mortality, cardiovascular events without increase significantly the risk of cancer, compared to cDMARDs.

Cardiovascular safety findings in patients with rheumatoid arthritis treated with tofacitinib, an oral Janus kinase inhibitor.

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). The implications of treatment with tofacitinib on cardiovascular (CV) risk in RA are unknown. Therefore, CV adverse events (AEs), and blood pressure and lipid level changes, in tofacitinib-treated patients with RA were evaluated. Data were pooled from six Phase (P)3 studies (24 months) and two open-label long-term extension (LTE) studies (60 months) of tofacitinib in patients with RA and inadequate response to DMARDs. Tofacitinib was administered alone or with non-biologic DMARDs. CV events, including major adverse CV events (MACE: CV death and non-fatal CV events) and congestive heart failure (CHF), were assessed by a blinded adjudication committee. Overall, 4271 patients from P3 studies and 4827 enrolled from P2/P3 studies into LTE studies were evaluated, representing 3942 and 8699 patient-years of exposure to tofacitinib, respectively. Blood pressure remained stable over time across studies. The number of investigator-reported hypertension-related AEs in tofacitinib-treated patients was low in P3 studies (Months 0-3: 2.8%; Months 3-6: 1.4%; >6 months: 2.8%). Across studies, lipid level increases were generally observed within 1-3 months of treatment and stabilized thereafter. Patients with events (incidence rate [IR]/100 patient-years) for MACE and CHF, respectively, were: 23 (0.58) and 9 (0.23) in P3 studies, and 32 (0.37) and 8 (0.09) in LTE studies; IRs were comparable with placebo (P3) and did not increase over time (LTE). Tofacitinib was associated with a low incidence of CV events in a large Phase 3 program, including LTE studies. Further long-term studies are underway.

Ultrasound power Doppler synovitis is associated with plasma IL-6 in established rheumatoid arthritis

Background and objective: Cytokines have an important role in the pathogenesis of rheumatoid arthritis (RA). Although plasma levels of IL-6 have been related to musculoskeletal ultrasound (MSUS) synovitis in early DMARD-naïve RA, there are no similar studies in established disease. Methods: 64 RA patients treated with non-biological DMARDs and 30 healthy controls were included in this prospective cross-sectional study. A blood sample was taken before evaluation of disease activity (DAS28) and ultrasonography (all tests performed in a blinded fashion). MSUS was performed by one of two ultrasound-trained rheumatologists on 10 joints of both hands. Gray scale (GS) and pD (power Doppler) synovitis were evaluated using a semi-quantitative scale (0–3) in individual joints, and their sum (score 10) was calculated. Plasma cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN-γ, and VEGF) were quantified by flow cytometry. Results: Levels of all cytokines, excepting VEGF, were significantly higher in RA patients than in controls (P⩽0.05). In RA patients, IL-6, but not other cytokines, correlated positively with DAS28 and swollen joint count (P⩽0.01), as well as with 10-joint pD score, and GS and pD of both wrists (P<0.01 for all tests). In multiple linear regression, the association of IL-6 with 10-joint pD score was maintained even after adjustment for DAS28. However, there was no correlation of IL-6 with tender joint count, 10-joint GS score, or presence of erosions. Conclusion: We demonstrated an association of inflammatory findings on MSUS and plasma IL-6 independently of DAS28 in established RA.

Assessment of the Therapeutic Effect of Total Glucosides of Peony for Juvenile Idiopathic Arthritis: A Systematic Review and Meta-Analysis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children; some clinical trials have reported the effects of total glucosides of peony (TGP) in the treatment of JIA. However, no systematic review has yet been conducted. In this study, we assessed the efficacy and safety in patients with JIA enrolled in randomized controlled trials (RCTs) of TGP. We extracted data for studies searched from 8 electronic databases that were searched and also evaluated the methodological quality of the included studies. We assessed the following outcome measures: overall response rate, pain, tender joint count (TJC), swollen joint count (SJC), duration of morning stiffness (DMS), grip strength (GS), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse effects (AEs) in short term (4–8 weeks), intermediate term (9–26 weeks), and long term (>26 weeks). The final analysis showed that TGP acted as a unique nonbiologic disease-modifying antirheumatic drug (nonbiologic DMARD), and its therapeutic effects were safe and efficacious for the treatment of JIA with few AEs. However, more high-quality RCTs are needed to confirm these therapeutic effects.

Analysis of drug prescribing trends in treatment of rheumatoid arthritis at a tertiary care hospital, Karnataka

Background: This study proposes compilation, analysis of pattern, trend, rationality and frequency of use of drugs in the treatment of rheumatoid arthritis with emphasis on available treatment regimens inclusive of primary and adjunctive therapy. Methods: The study records relevant data obtained from medical case records of patients suffering from RA above 15 years age excluding pregnancy and other arthritis, attending orthopedic OPD at KVGMC, Sullia (D.K), Karnataka, prospectively for a period of 15-18 months starting from December 2013 to June 2015. Results: 217 patients suffering from RA were analyzed and recorded. RA was more common among the age group of 45 to 50 with female predominance (64%). RF positivity was seen in 42% cases. Out of 11 classes of drugs prescribed DMARDs (249), corticosteroids (225) and analgesics (217) played major role in treatment outcome. Non-biological DMARDs (94%) were more commonly prescribed, of which methotrexate (120) & hydroxychloroquine (128) were frequently administered. Very few patients received biological DMARDs like etanercept and infliximab. Both oral and IV preparations of corticosteroids were administered. Among the adjuvant group of drugs NSAIDs (130), opioids (53), Muscle relaxants (33), pregabalin (26), sedative/hypnotics (102) nutritional supplements (214), anti-gastric (201), antiemetic’s (13), anti-histamines (4) were prescribed accordingly. Treatment outcome was assessed at the end of 15 months and 163 patients were relieved from symptoms but no remission but there was significant association between treatment outcome and duration of treatment with DMARDs. Conclusions: The treatment outcome and the duration of illness have significantly improved with rational use of DMARDs. Thus the study highlights and creates awareness on rational use of therapeutic agents available for treatment of RA and provides feedback to the prescriber.