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Objective Two surveys were conducted with patients with rheumatologic diseases to evaluate perceptions of different routes of administration (intravenous [IV] or subcutaneous [SC]) for biologic therapy. Methods In Survey I, patient preferences toward biologic treatment were evaluated at a rheumatology practice in Buffalo, New York. In Survey II, Canadian patients enrolled in the BioAdvance patient support program and scheduled to receive IV biologic therapy were asked about their opinions of IV treatment. Results In Survey I, 243 rheumatology patients participated. Median patient age was 60 years, 76% were female, and 44% were naive to treatment with biologic agents. Among biologic-naive patients, the majority (56%) were open to either SC or IV treatment; biologic-naive women were more likely than men to express a preference for the route of administration. In Survey II, 1,598 patients from the BioAdvance program (including 306 rheumatology patients) completed the full survey. Among the rheumatology patients, the median age was 49 years, 58% were female, and 61% had not previously taken biologics before enrolling in the BioAdvance program. The median rating of IV favorability (on a 10-point scale, with higher numbers indicating increased favorability) recalled by rheumatology patients was 5 prior to their first program infusion, which increased to 9 after multiple treatment infusions. Conclusion These survey results indicate that patients with rheumatoid arthritis are generally open to IV treatment and express high satisfaction with IV therapy. Additional patient and provider education may improve shared decision-making regarding biologic therapy administration options.

Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA). Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation. Trends in mean Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores from visits following dose escalations were evaluated. In patients who received 2 or 3 dose escalations, the initial (1 or 2) dose escalations resulted in reduced mean CDAI scores, but subsequent escalations did not further reduce disease activity. In patients who received ≥ 4 dose escalations, mean CDAI scores did not further reduce disease activity over time. Mean HAQ scores were stable over time in patients who received 2 or 3 dose escalations. In patients who received ≥ 4 dose escalations, mean HAQ scores decreased following 1 dose escalation but progressively increased following subsequent dose escalations. Initial dose escalations (from 3 mg/kg to the equivalent of approximately 5 to 7 mg/kg) may be useful in controlling disease activity; however, there may be diminishing clinical benefit of further escalations, which can also increase the potential risk for infection and increase incremental drug costs. • Initial infliximab dose escalations (1 to 2) may be useful in lowering disease activity in patients with rheumatoid arthritis. • There does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.

Lorie A Ellis,1 Elisabetta Malangone-Monaco,2 Helen Varker,3 Diana Stetsovsky,3 Maureen Kubacki,1 Raphael J DeHoratius,1,4 Shelly Kafka1 1Real World Value and Evidence, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 2Life Sciences, IBM Watson Health, Armonk, NY, USA; 3Life Sciences, IBM Watson Health, Cambridge, MA, USA; 4Janssen Immunology, Medical Affairs, Sidney Kimmel School of Medicine, Thomas Jefferson University, Philadelphia, PA, USA Purpose: The objectives of this study were to evaluate and compare treatment patterns and infusion-related health care resource expenditures for rheumatoid arthritis (RA) patients initiating golimumab for intravenous use (GLM-IV) and infliximab (IFX) therapy and to assess cost implications from the commercial perspective.Methods: Adult RA patients with a new episode of GLM-IV or IFX treatment between January 1, 2014 and March 31, 2016 were identified from MarketScan databases and evaluated for maintenance infusion intervals and related costs of treatment. IFX and GLM-IV patients were matched 1:1 on index medication treatment duration, gender, payer type, prior biologic use, and post-index methotrexate use. Paid amounts for drugs and associated administration costs were applied to treatment group dosing patterns.Results: Final matched treatment groups included 547 GLM-IV and 547 IFX patients (mean age = 55–56 years). Mean (SD) follow-up was 609 (161) days for GLM-IV and 613 (163) days for IFX. Treatment duration was 396 (240) days for GLM-IV and 397 (239) days for IFX. Overall, 80% of GLM-IV and 39% of IFX maintenance infusions were given approximately every 8 weeks; and 6% of GLM-IV and 53% of IFX maintenance infusions occurred more frequently than every 8 weeks (P

Purpose For patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF. Methods Patient charts (n = 113) were collected from five US-based rheumatology practices. Patient demographics, treatment characteristics, infliximab and intravenous golimumab utilization data, and Clinical Disease Activity Index (CDAI), Patient Global Assessment (PtGA), Physician Global Assessment (PhGA), and Routine Assessment of Patient Index Data (RAPID3) scores were extracted from charts. The effectiveness of intravenous golimumab was assessed by comparing disease activity status pre- and post-initiation of intravenous golimumab therapy. Findings Significant decreases in patient disease activity were observed following treatment with intravenous golimumab. Mean CDAI and PhGA scores significantly decreased, and a significantly increased proportion of the population exhibited low disease activity or remission in the post intravenous golimumab period (p

Background Patient perceptions of treatment success, including satisfaction/preference, may complement clinical efficacy assessments. Objective Our objective was to evaluate satisfaction with subcutaneous golimumab and its auto-injector in patients with rheumatoid arthritis (RA) and an inadequate adalimumab/etanercept response. Methods In the multicenter, assessor-blinded GO-SAVE study, 433 patients with active RA (28-joint Disease Activity Score incorporating erythrocyte sedimentation rate [DAS28-ESR] ≥ 3.6 and six or more swollen and six or more tender joints) despite methotrexate and past adalimumab/etanercept treatment received open-label subcutaneous golimumab 50 mg every 4 weeks (q4w) through week 12. Week 16 responders (DAS28-ESR improvement from baseline > 1.2 and score ≤ 3.2) continued therapy through week 52; nonresponders were randomized (1:2) to double-blind subcutaneous golimumab 50 mg q4w or intravenous golimumab 2 mg/kg [weeks 16, 20, every 8 weeks (q8w)]. Patients rated satisfaction with their injection experience on a 5-point scale (1 = very dissatisfied; 5 = very satisfied) at screening, week 8 (all enrolled patients), and week 44 (for patients continuing open-label subcutaneous golimumab 50 mg q4w). Discomfort, pain, stinging, burning, and redness related to injection were assessed (none, mild, moderate, severe). Results Similar proportions of patients (N = 433) had most recently received adalimumab (50.3%) or etanercept (49.7%) prior to golimumab. Overall satisfaction (somewhat/very) with the golimumab injection experience was reported by 84.4% of patients at week 8 versus 63.4% of patients who were satisfied with prior adalimumab/etanercept. Patients receiving open-label subcutaneous golimumab through week 44 (N = 75) reported much less discomfort (60.9%), redness (60.9%), pain (59.4%), stinging (67.2%), and burning (65.6%) with the golimumab injection than with their previous tumor necrosis factor antagonist medication injection. Conclusion Most patients with RA receiving golimumab following adalimumab/etanercept inadequate response were satisfied with their overall golimumab experience, including its auto-injector versus their previous injection device. Clinical trials.gov NCT01004432; EudraCT 2009-010582-23. Electronic supplementary material The online version of this article (10.1007/s40271-018-0297-5) contains supplementary material, which is available to authorized users.

Norman B Gaylis,1 Joanne Sagliani,1 Shawn Black,2 Kezhen L Tang,3 Raphael DeHoratius,2,4 Wesley A Kafka,2 Dennis Parenti2 1Arthritis & Rheumatic Disease Specialties, Aventura, FL, USA; 2Medical Affairs Rheumatology, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 3Quantitative Sciences, Janssen Research & Development, LLC, Spring House, PA, USA; 4Department of Medicine and Pharmacology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA Objective: To evaluate patient perspectives regarding utilization of intravenous (IV) therapy for inflammatory arthritis (IA).Methods: This was a single-center, noninterventional, patient questionnaire-based study of adult IA patients currently receiving IV biologics. At a single visit, patients completed the questionnaire comprising 30 questions centered on their experience receiving an intravenously administered therapy to treat their IA. The questionnaire included questions on patient demographics, disease characteristics, and previous biologic treatment for IA (subcutaneous [SC] and IV). Patients rated their level of agreement with statements regarding satisfaction with current IV biologic therapy and potential advantages and disadvantages of IV biologic therapy using a 5-point Likert scale (1=strongly disagree, 5=strongly agree).Results: One hundred patients were enrolled and completed the survey; 66% were female and the mean age was 58 years. Before IV treatment, 97% of patients received information regarding therapy options. Ninety patients ranked their satisfaction with current IV therapy as 4 or 5. The proportion of patients with an “extremely favorable” perception of IV therapy increased from 33% to 71% following initiation of their current medication. Thirty-one patients had previously received SC therapies to treat their IA.Conclusion: These results demonstrated an overall favorable perception of IV therapy among this patient population. Patients previously treated with SC therapy also had a positive shift in the perception of IV therapy after initiating IV therapy. Patients’ perception and preference for treatment options should be highly considered by the treating physician during or as part of a shared decision-making process. Keywords: intravenous, patient satisfaction, arthritis, biologic therapy

Evaluate efficacy of infliximab with response-driven dosing in patients with active RA.Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26.NCT 00714493, EudraCT 2007-003288-36.Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change -1.1 [1.15]; p 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients.Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial.Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.

Objective To investigate whether treatment with abetimus delays renal flare in patients with lupus nephritis. Secondary objectives included evaluation of the effect of abetimus on C3 levels, anti–double-stranded DNA (anti-dsDNA) antibody levels, use of high-dose corticosteroids and/or cyclophosphamide, and major systemic lupus erythematosus (SLE) flare. Methods We conducted a randomized, placebo-controlled study of treatment with abetimus at 100 mg/week for up to 22 months in SLE patients. Three hundred seventeen patients with a history of renal flare and anti-dsDNA levels >15 IU/ml were randomized to a treatment group (158 abetimus, 159 placebo); 298 (94%) were enrolled in the intent-to-treat (ITT) population (145 abetimus, 153 placebo), based on the presence of high-affinity antibodies for the oligonucleotide epitope of abetimus at baseline screening. Results Abetimus did not significantly prolong time to renal flare, time to initiation of high-dose corticosteroid and/or cyclophosphamide treatment, or time to major SLE flare. However, there were 25% fewer renal flares in the abetimus group compared with the placebo group (17 of 145 abetimus-treated patients [12%] versus 24 of 153 placebo-treated patients [16%]). Abetimus treatment decreased anti-dsDNA antibody levels (P < 0.0001), and reductions in anti-dsDNA levels were associated with increases in C3 levels (P < 0.0001). More patients in the abetimus group experienced ≥50% reductions in proteinuria at 1 year, compared with the placebo group (nominal P = 0.047). Trends toward reduced rates of renal flare and major SLE flare were noted in patients treated with abetimus who had impaired renal function at baseline. Treatment with abetimus for up to 22 months was well tolerated. Conclusion Abetimus at 100 mg/week significantly reduced anti-dsDNA antibody levels but did not significantly prolong time to renal flare when compared with placebo. Multiple positive trends in renal end points were observed in the abetimus treatment group.

Acquired inhibitors of factor VIII have rarely been reported in the presence of systemic lupus erythematosus (SLE). Treatment is usually corticosteroids, with or without immunosuppressive agents such as cyclophosphamide or azathioprine. We report here case histories of 2 patients, one with documented SLE, the other with a forme fruste of SLE. Both patients had inadequate responses to corticosteroids and immunosuppressive agents. Both responded to intravenous immunoglobulin, with a decrease in their titers of factor VIII inhibitor and significantly decreased frequency of bleeding episodes despite persistent low-level inhibitor titers. Better control of their SLE symptoms and findings was also observed. Previously reported treatments of acquired factor VIII inhibitors in SLE are discussed.

Members, guests, and staff, it has been my utmost honor and privilege to serve as President of the American College of Rheumatology this past year. I would like to thank, first of all, my family for their love, guidance, understanding, and patience during the numerous trips requiring time away from home. As I was preparing this talk, I realized that, with time, many of the problems that face us as rheumatologists change very little from year to year but affect different segments of our membership to varying degrees. Therefore, when looking for a title for this address, the term “Ex nihilo nihil fit” from Shakespeare’s King Lear came to mind: “Do nothing and nothing is what you get” or, more loosely translated, “Do nothing and you will not fail.” (1). From the onset of our organization in Philadelphia almost 70 years ago and the transition to the American College of Rheumatology 15 years ago, the ACR has never adopted this philosophy. As a diverse organization we encompass practitioners, clinician educators, both clinical and basic researchers, as well as rheumatology health professionals from varied sectors of the health care delivery system, all of whom have unique problems. Over the next few minutes, I would like to review where we have been and where, in my opinion, we should be going as an organization. I will do this in the context of phone calls received by the President over the past year from various segments of our organization. The first has to do with a call stating the ACR has done nothing with regard to proposed Medicare changes in reimbursement for infusion therapy. The caller wanted the ACR to lobby for maintaining the status quo. On the surface this seemed to be a reasonable request to the caller. Further discussion led to the following insights for the caller: In a previous time of legislative cutbacks, the ACR under the leadership of one of our past Presidents, Ron Kaufman, had the foresight to know that changes occur most frequently from within. The ACR became involved in all the important committees that report to the Centers for Medicare and Medicaid Services. Through hard work and education of other committee members, reimbursement to rheumatologists increased when other specialties remained flat or decreased. This was based on the practice expense of rheumatologists and the time required to see our patients. CPT codes that more clearly reflect the types of injections we do were put into effect to again facilitate reimbursement to rheumatologists that was previously being denied. Is reimbursement fair? Of course not! However, it would have been worse if we did not, as an organization, proactively get involved in the thankless task of interacting on the various national committees to educate others in what we do as rheumatologists. With regard to therapy, our position has been consistent and vocal. The message has always been equal access to therapy for all patients. As a result of research done by our members, patients have access to therapies that, for the first time, have remarkable benefit. Is it right that patients on Medicare without a prescription plan do not have access to injectable therapies? Of course not! The policy of covering only infusion therapies denies Medicare recipients access to other potentially efficacious therapies. Like it or not, medicine has become a business. Just like other businesses, we cannot remain in business if we lose money because time and costs are not reimbursed; thus, the impetus by the College to get fair reimbursement for infusions, whether done by rheumatologists or other specialists. Will reimbursement remain the same? Of course not, but it will more accurately reflect what we do as rheumatologists. The College needs to make its membership more aware of what it Presented at the 67th Annual Scientific Meeting of the American College of Rheumatology, October 27, 2003. Raphael J. DeHoratius, MD: Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania: President, American College of Rheumatology, 2002–2003. Address correspondence and reprint requests to Raphael J. DeHoratius, MD, Jefferson Medical College, Thomas Jefferson University, Room 613 Curtis, 1015 Walnut Street, Philadelphia, PA 19107-5099. E-mail: raphael.dehoratius@jefferson.edu. Submitted for publication October 29, 2003; accepted October 29, 2003.

Background Dose escalation is a common strategy for patients (pts) having an inadequate response to a medication. Objectives To examine low disease activity (LDA) among pts receiving infliximab (IFX) who did and did not escalate therapy above 3mg/kg in CORRONA, a US national registry of rheumatoid arthritis (RA) pts. Methods We identified all RA pts who initiated IFX on or after 6/2009 at a dose ≤3mg/kg and with moderate or high disease activity (CDAI>10). Eligible pts required at least 6 mos of follow-up after initiation or after dose escalation. Dose escalation was defined as an increase of >1mg/kg or reduction in infusion intervals by ≥1 wk. We divided pts into 3 groups: pts achieving LDA (CDAI ≤10) without dose escalation; pts not achieving LDA and not dose escalating; pts dose escalating. The last group was further divided into pts achieving LDA after dose escalation and pts not achieving LDA after dose escalation. We compared the populations at time of initiation by demographics, BMI in categories of normal (BMI Results There were 286 pts who met inclusion criteria. 124 (43.4%) reached LDA without escalation; 50 (17.5%) either switched without escalation or had not reached LDA by at least 9 mos; 112 (39.2%) escalated. Of the escalators, 64 (57.1%) reached LDA and 48 (42.9%) switched or did not reach LDA by at least 9 mos. Pts who reached LDA without escalation were more likely to be biologic naive (67.7%) than those who escalated but did not reach LDA (45.8%, p=0.008). Pts reaching LDA without escalation had lower disease activity measures at initiation (tender joints, physician global assessment, pt global assessment, pt pain) than pts not reaching LDA with or without escalation (p Conclusions Pts more likely to reach LDA without dose escalation are biologic naive and have lower disease activity measures at initiation. Both high BMI (obese) and diabetes are associated with requiring dose escalation to achieve LDA. In this analysis, ≤25% of patients received dose escalation beyond 8mg/kg/8wks, which may have clinical relevance. Acknowledgement Study sponsored by Corrona, LLC. Corrona RA registry has been supported thru contracted subscriptions in last 2 yrs by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, & UCB. Disclosure of Interest S. Cohen Grant/research support from: Amgen, Biogen-IDEC, BMS, Centocor, Genentech, Johnson & Johnson, Pfizer, Merck, and Roche, G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, R. Magner Employee of: Corrona, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, L. Ellis Employee of: Janssen Scientific Affairs, LLC, R. DeHoratius Employee of: Janssen Scientific Affairs, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Janssen Scientific Affairs, LLC, AstraZeneca, Celgene, Genentech, Novartis, Pfizer, Employee of: Corrona, LLC

Background Little is known about the influence of specific comorbidities on response to biologic therapy. Objectives To examine the impact of comorbidities on anti-TNF therapy efficacy in rheumatoid arthritis (RA) patients (pts) within the US CORRONA RA registry. Methods A retrospective cohort of adult RA pts with moderate-to-severe RA (CDAI>10) who initiated anti-TNF biologics after June 1, 2009 and had a 6 month follow up (in a window of 3–9 months) were included. Comorbidity assessments included a modified Charlson comorbidity index (CCI) [HIV status was not assessed]) and diagnoses of diabetes, cardiovascular disease (CV) and history of depression. Propensity score (PS) method was employed to match pts with and without select comorbidities. Variables used for PS matching were selected if standardized differences were ≥0.1 between groups. PS were stratified by line of therapy. The primary outcome was achievement of low disease activity (LDA) at 6 months (CDAI ≤10). Secondary outcomes included DAS28(ESR) LDA (DAS Results A total of 4064 anti-TNF initiations were included. For CCI, diabetes and CV, there were no significant differences in response in the matched populations. For patients with a history of reported depression (hxdep), LDA rates were significantly lower (29% for hxdep vs 39% for no hxdep, p Conclusions Of the comorbidities examined, a history of reported depression in RA patients is an indicator of lower response rates to TNFi. CDAI was primarily influenced by patient responses. Patient fatigue may be a manifestation of depression and explained response rate differences. Further analyses are needed to explore this relationship. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest D. Parenti Employee of: Janssen Scientific Affairs, LLC, G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, S. Kafka Employee of: Janssen Scientific Affairs, LLC, L. Ellis Employee of: Janssen Scientific Affairs, LLC, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: Janssen Scientific Affairs, LLC, AstraZeneca, Celgene, Genentech, Novartis, Pfizer, Employee of: Corrona, LLC, R. DeHoratius Employee of: Janssen Scientific Affairs, LLC

Background Pt-reported outcomes (PRO) are used to assess pt-related benefit in clinical trials. Inflammatory arthritis (IA) pts are equally receptive to intravenous (IV) or subcutaneous (SC) biologic treatment 1 . Objectives We obtained PRO data to understand characteristics of pts who receive IV biologic agents for IA. Methods This was a questionnaire-based study conducted at a rheumatology practice with extensive clinical trial experience. A total of 100 pts enrolled & are included in this final analysis. Inclusion criteria: a diagnosis of IA with IV biologic use for ≥3 mo; ≥18 yrs age; able to read, write & speak English, willing to complete the questionnaire & a signed informed consent form. IV biologic treatment was per clinical practice; there were no treatment assignments & study drug was not supplied. The questionnaire had 30 questions which pts completed prior to receiving a regularly scheduled dose of IV biologic. Results Mean (±SD) age of pts was 58.35 (±14.64) yrs with mean disease duration of 10.1 (±8.13) yrs (range 0.7–45 years). Pts were Caucasian (38%), African American (28%), Latino/Hispanic (22%), Asian/Pacific Islander (1%) & 11% not identified. IV biologics used were infliximab [IFX](71%), rituximab [RTX](12%), tocilizumab [TCZ](10%), abatacept [ABT](6%) & golimumab [GLM](1%). The mean duration of current IV therapy was 4.07 (±3.27) yrs (range 0.1 to 16.0 yrs). Pts9 favorability perception of IV therapy BEFORE & AFTER starting IV therapy is shown in the Figure. Amongst all pts, “Extremely favorable” increased (p Conclusions These results suggest that among IA pts receiving IV biologic therapy for treatment of IA, there is a high degree of pt satisfaction, including a similar favorability perception of IV therapy among pts who switched from a SC to an IV biologic. Our results support the concept that when there is a shared decision making discussion with pts regarding biologic treatments, the option of IV therapy should be an essential part of that discussion & that the IA pts9 perspective should be given meaningful consideration. References Bolge SC et al Arthritis Rheum 2013;65 Suppl 10:1023 Disclosure of Interest N. Gaylis Grant/research support from: Janssen Scientific Affairs, LLC, J. Sagliani Grant/research support from: Janssen Scientific Affairs, LLC, S. Black Employee of: Janssen R & D, LLC, K. Tang Employee of: Janssen R & D, LLC, R. Dehoratius Employee of: Janssen Scientific Affairs, LLC, D. Parenti Employee of: Janssen Scientific Affairs, LLC

Improving the quality of life for people with rheumatic disease involves timely identification of problem areas and application of appropriate interventions. In response to a 1987 Commonwealth of Pennsylvania study, which reported a wide variety of unmet needs in arthritis patients and their families, the Arthritis Problem Indicator (API) was developed. It is a single-page, self-report, low-cost tool. A mixed rheumatology population (n = 50) and their primary care physicians participated in a pilot study. The study revealed that the seven most common areas of patient concern were pain, weight control, sleep, mobility/walking, activities of daily living, community access, and depression/anxiety. The physicians reported that the patient's answers on the API led them to initiate new treatment or referral for 32% of the patients. The physicians also stated that for 80% of the patients, the API was helpful in providing information about the patient. The API is easily interpreted by health professionals and designed to be an indicator of problem areas frequently associated with arthritis.

Case Report A 42-year-old man was transferred to our institution for management of severe ulcerations of the lower extremities thought to be secondary to vasculitis. Three months previously, the patient was hit on the left shin by a soccer ball. The next day, his left pretibial region became erythematous and swollen. He was given cephalexin for presumed cellulitis, and the erythema improved but the swelling did not. Within a few days, the erythema returned and the swelling extended to his calf. Small, tight bullae formed over the affected skin. His right leg also began to swell and blister. The patient developed generalized edema and decreased urine output. He was admitted to an outside hospital. The patient had hypertension and a baseline creatinine level of 2 mg/dl. Medications included amlodipine, furosemide, and acetaminophen/propoxyphene napsylate. There were no known drug allergies. Social and family histories were noncontributory. Upon admission, the patient was afebrile and vital signs were normal except for a blood pressure of 150/90 mm Hg. The examination was remarkable for erythema of the lower extremities with 3 pitting edema and mild flexion contractures of the knees. The skin below the knees was covered with scattered bullae, indurated violaceous patches, and ulcers. Initial laboratory results are shown in Table 1. A portable chest radiograph showed cardiomegaly with clear lung fields. Renal ultrasound revealed a right renal cyst, increased cortical echogenicity, and diminished renal cortices. Cephalexin was continued, and dialysis was initiated. Results of blood and urine cultures were negative. Cultures of the wounds grew mixed bowel and skin flora. Erythrocyte sedimentation rate was 85 mm/hour. Hepatitis B and C serologies, antinuclear antibody, antineutrophil cytoplasmic antibodies, and cryoglobulins were negative. Serum protein electrophoresis was normal. Intact parathyroid hormone (PTH) was increased at 196.5 pg/ml (normal range 10–55 pg/ml). There was no evidence of venous thromboembolism on duplex ultrasonography of the lower extremities or by a ventilation/perfusion scan. Transthoracic echocardiogram showed no evidence of endocarditis, atrial myxoma, or atheroembolic disease. Despite ciprofloxacin and ceftazidime, whirlpool treatments, and wound debridement, numerous ulcers with black eschar and indurated, erythematous margins developed below the knees. New violaceous and indurated lesions progressed proximally to involve the thighs followed by the lower abdomen. Punch biopsy samples of the left and right thigh were reported as necrotizing vasculitis. Treatment with methylprednisolone 60 mg intravenously every 6 hours was begun. The histopathologic findings, however, also included focal fat necrosis and a patent blood vessel with mural calcification, features suggesting calciphylaxis. A repeat punch biopsy sample of the thigh obtained 1 week later for immunofluorescent studies showed vascular and perivascular fibrin deposits that were suggestive of atrophie blanche from stasis dermatitis or livedo vasculitis. Mycophenolate mofetil was initiated and subsequently discontinued days later, when blood cultures grew Pseudomonas and Enterobacter. Computed tomography of the chest, abdomen, and pelvis revealed no masses or lymphadenopathy. Rheumatoid factor, anticardiolipin antibodies, lupus anticoagulant, and anti–double-stranded DNA antibody were repeatedly negative. Serum C3 and C4 were normal. Three months after the initial admission the patient was transferred to our institution for further treatment. He was stable and afebrile but in severe pain. The physical examination revealed extensive skin involvement (Figure 1). A necrotic lesion was present over the left lower abdomen Supported by the South Jersey Lupus Foundation. Dana Jacobs-Kosmin, MD: Albert Einstein Medical Center, Philadelphia, Pennsylvania; Raphael J. DeHoratius, MD: Thomas Jefferson University, Philadelphia, Pennsylvania. Address correspondence to Dana Jacobs-Kosmin, MD, Einstein Arthritis Center, 5501 Old York Road, Korman 103, Philadelphia, PA 19141. E-mail: jacobkd@einstein.edu. Submitted for publication May 10, 2006; accepted in revised form August 31, 2006. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 57, No. 3, April 15, 2007, pp 533–537 DOI 10.1002/art.22616 © 2007, American College of Rheumatology

Rosai-Dorfman disease (RDD), also known as sinus histocytosis with massive lymphadenopathy, is a clinically benign, frequently chronic, painless lymphadenopathy. It can also involve extranodal sites. We describe a 37-year-old man with a recent diagnosis of systemic lupus erythematosus and antiphospholipid antibody syndrome who had lacrimal gland and orbital involvement and nodal and extranodal sites with RDD.

Objective To examine the relationship between changes in anti–double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. Methods Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer ≥15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. Results Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26–68%, nominal P = 0.0007) and a 53% reduction (95% CI 33–69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). Conclusion Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.

Much of our education about endocrine disorders focuses on their diagnosis and treatment. Although the musculoskeletal manifestations of endocrine disorders are well documented, they are often overlooked. This review will discuss new developments regarding those rheumatic manifestations.Diabetic research is investigating connective tissue alterations in hand syndromes. A recent review elucidated the natural history of diabetic muscle infarction. Research has identified factors that stimulate osteoblast activity in diffuse idiopathic skeletal hyperostosis and bone loss in diabetics. Accumulating evidence documents thyroid disease coexisting with connective tissue disorders. Reports document cases of vasculitis occurring after propylthiouracil treatment. Finally, data clarifies the effects of thyroid dysfunction, hyperparathyroidism, acromegaly and hypercortisolism on bone.Current research mainly relates to the effects of endocrine disorders on bone. As we advance our understanding of mechanisms that lead to rheumatic disorders in endocrine disease, we will improve our ability to treat them.

Actinobacillus ureae, formerly known as Pasteurella ureae, is a rare human pathogen. We describe a case of septic arthritis and abscess formation caused by this unusual organism in a patient with rheumatoid arthritis, who was being treated with tumor necrosis factor-alpha inhibitors.

The aim of this study was to evaluate whether corticosteroid use is the etiological agent in acute pancreatitis in patients with systemic lupus erythematosus, or whether it is related to the underlying connective tissue disorder. Hospital admissions at Thomas Jefferson University Hospital between 1982 and 2002 that carried the dual diagnosis of systemic lupus erythematosus and pancreatitis were identified, and demographic data, clinical interventions and parameters of clinical progression of their disease were identified. From 2947 admissions with systemic lupus erythematosus 25 (0.85%) were diagnosed as having acute pancreatitis; 76% of cases had active systemic lupus erythematosus on presentation, with an average of 4.4 organ involvement, and a clustering of renal disease (56%), pleural effusion (48%) and arthritis (44%) in these patients. Fifteen patients with active disease and three whose disease was inactive received increased doses of corticosteroids, and four active cases and one inactive one stayed on the same doses. Two inactive patients received no corticosteroids before or after the diagnosis of pancreatitis. Eighty-two percent of patients had clinical and laboratory improvement on the higher or maintenance dose of corticosteroids. We therefore concluded that acute pancreatitis is a rare manifestation of systemic lupus erythematosus, and corticosteroids do not appear to be the etiological agent.

Objectives GO-SAVE is a Ph3b, multi-center, switch assessment of SC and IV golimumab (GLM) in RA pts who have inadequate disease control despite treatment with etanercept (ETN) or adalimumab (ADA). Primary objective is to assess the efficacy of GLM at wk14 in pts with active RA and an inadequate response to ETN or ADA. Methods Pts with active RA (DAS28 score ≥3.6 with ≥6 swollen and ≥6 tender joints) who were currently receiving MTX and ETN or ADA were switched to GLM. Pts entered the screening period 6wks prior to receiving GLM (wk -6), remained on their original anti-TNFa, and re-screened again at wk 0. All eligible pts were actively switched to open-label GLM 50mg SC q4w at wk0. At wk16, pts who achieved a good DAS28-ESR response continued to receive open-label GLM 50mg SC q4wks +MTX through wk48 (Grp 1). Those with DAS28-ESR response classified as moderate or nonresponse were randomized (1:2) to double-blind treatment grps: GLM 50mg SC q4wks + MTX (Grp 2a) or GLM 2mg/kg IV q8wks (with a loading dose at wk20) +MTX (Grp 2b). Efficacy and safety evaluations were conducted through wk52. Results 433 pts were enrolled at wk0. All were included in the mITT population analysis. 358 pts (82.7%) were female; mean age was 55.7±11.5 yrs and mean disease duration was 10.7±9.8 yrs. At baseline, mean ± SD number of swollen and tender joints was 18.4±11.8 and 31.3±17.0, resp, and mean DAS28-ESR score was 6.2±0.9. Prior to GLM, 174 (40.2%) pts had received only ETN, and 186 (42.9%) had received only ADA; 73 (16.8%) pts had been previously exposed to both ETN and ADA, but not concomitantly. At wk14, 151 of the 433 pts (34.9%; 95% CI: 30.4%, 39.4%) achieved the primary outcome of an ACR20 response; a moderate or good EULAR response was achieved in 224pts (51.7%; 95% CI: 47.0%, 56.4%) with a mean DAS28-ESR improvement of -1.5 (95% CI: -1.6, -1.3, p Conclusions GLM significantly improves signs and symptoms in pts with moderate or severe RA responding inadequately to ETN or ADA. Over a third of pts achieved an ACR20 and over half achieved a DAS28-defined EULAR response beyond the results with their previous therapy. No difference was observed between IV and SC GLM. GLM was safe and well-tolerated. Disclosure of Interest : J. Huffstutter Grant/research support: Amgen, Janssen, and Pfizer., Speakers bureau: Janssen and UCB., S. Kafka Grant/research support: same companies, as well as Lilly, Speakers bureau: Pfizer, Abbvie, Janssen, Amgen, BMS, Genentech, UCB, L. Brent Grant/research support: Janssen, Speakers bureau: AbbVie, Genentech, M. Matucci-Cerinic Grant/research support: Janssen, K. Tang Employee of: Janssen Research & Development, LLC., J. Wang Employee of: Janssen Research & Development, LLC., D. Decktor Employee of: Janssen Scientific Affairs, M. Chevrier Employee of: Janssen Scientific Affairs, T. Sprabery Employee of: Janssen Scientific Affairs, R. DeHoratius Employee of: Janssen Scientific Affairs DOI 10.1136/annrheumdis-2014-eular.3766

OBJECTIVE To give a comprehensive review of transverse myelopathy (TM), a rare but serious condition reported in 1–2% of patients with systemic lupus erythematosus (SLE). METHODS 14 patients with SLE and TM were evaluated and 91 additional cases published in the English and German literature reviewed. RESULTS TM presented either as the initial manifestation or within five years of the diagnosis of SLE. Most patients presented with a detectable sensory deficit at the thoracic level. In our 14 patients, 22% of the patients showed complete neurological recovery, whereas in the total patient population of 105 (our cases plus those reviewed in the literature), complete recovery was observed in 50%, partial recovery in 29% and no improvement or deterioration in 21%. Treatment with intravenous methylprednisolone followed by cyclophosphamide seemed to be most effective. Seventy per cent of the total patient population had abnormal magnetic resonance imaging findings. In our group of 14 patients, those with higher disease activity (measured by the SLAM) at onset of TM were treated more aggressively (for example, with plasmapheresis and intravenous pulse cyclophosphamide). TM in our patients was associated with antiphospholipid antibodies in 43% of the cases as compared with 64% of the total patient population. Optic neuritis occurred in 48% of the total patient population with SLE and TM, suggesting an association. CONCLUSIONS TM in SLE is a poorly understood entity. Outcome might be more favourable than previously suggested. There is an association of TM with antiphospholipid antibodies in SLE patients. Treatment including intravenous cyclophosphamide may improve the final outcome. This report emphasises the need for multicentre trials to establish guidelines for optimal treatment.

Investigation of the cellular immune function in patients with rheumatic diseases is important in elucidating the pathogenesis of the disease processes and in determining the associated abnormalities of recognition and regulation exerted by the immune system. However, because of the lack of specificity and the variations noted from laboratory to laboratory, tests of cellular immune function are, at present, of little value in the laboratory diagnosis of these diseases. The abnormalities found in the rheumatic diseases occur with many autoimmune diseases and other inflammatory states. The common pathway of immune abnormalities appears to be influenced by several factors. They include several genetic loci, possible environmental factors, and immunologic mechanisms, which appear to interact in an intimate way to induce various autoimmune diseases.

Peripheral blood thymus-dependent (TL) and bone marrow-dependent lymphocytes (BL) were measured in healthy control subjects and patients with acute or chronic hepatitis with and without hepatitis B antigen (HBAg) and in two chronic carriers of HBAg. A significant decrease in TL occurred in patients with acute or chronic hepatitis but not in healthy HBAg carriers. The decrease occurred in all forms of acute hepatitis and was transient in patients who recovered. TL depression occurred in both chronic persistent and chronic aggressive hepatitis and did not correlate with disease activity nor mode of treatment. In both acute and chronic hepatitis, decreases in TL occurred independently of serum autoantibodies. These findings emphasize the potential importance of host responses in determining the outcome of viral hepatitis.

The role of abnormal numbers and function of lymphocyte subsets in SLE remains, to date, unclear. Evidence exists for both functional T lymphocyte and B lymphocyte defects although the data for T lymphocyte defects appear more compelling. The role of autoantibodies on these cellular defects is also unclear. They may take on an important pathophysiologic role in depletion of certain lymphocyte subsets with subsequent alteration of function or they may, in fact, be interesting epiphenomena since an inverse relationship of depressed T lymphocyte numbers and function to increased levels of LCTA are frequent. Many other factors clearly influence lymphocyte function and disease expression including genetics and endocrine factors. As methodologies improve, a clearer understanding of the pathogenesis of SLE will emerge.

A rabbit model of diffuse proliferative lung disease induced by one intravenous injection of complete Freund's adjuvant was used to study the possible phlogistic effects of human anti-γ-globulins. When induction of proliferative lung disease was followed by intravenous administration of human γM anti-γ-globulins, considerable increment in perigranulomatous inflammation along with alveolar wall and arteriolar anti-γ-globulin deposition was noted. Four of 10 animals thus treated showed segmental hemorrhagic pulmonary infarctions. Control animals in which the induction of diffuse proliferative lung disease was followed by administration of serologically inactive normal human γM showed no accentuation of gross or microscopic pulmonary lesions and no specific pulmonary deposition of human γM globulins. These experiments suggest that human γM anti-γ-globulins fix in alveoli and arterioles near areas of active subacute or chronic pulmonary inflammation and are capable of accentuating inflammatory response and vascular injury.

Plasmapheresis was used as the sole treatment modality in 4 patients with systemic lupus erythematosus. The presence of circulating immune complexes in this group of patients was not predictive of response to plasmapheresis. Lymphocytotoxic antibody levels fell in 3 of the 4 patients, and no consistent changes in T lymphocytes, T lymphocyte subsets, complement, or immunoglobulin levels were observed. Followup during the subsequent 6 months showed deterioration in clinical and laboratory parameters in all 4 patients, and the protocol was discontinued. Plasmapheresis without concomitant therapy may be detrimental to certain patients with systemic lupus erythematosus.

We investigated the role of suppressor cells in the depressed cellular immunity of patients with sarcoidosis. The mean response in 16 patients with active sarcoidosis to three concentrations of phytohemagglutinin was significantly (P less than 0.01) less than control values. Passage of the cells over glass wool resulted in a 116% increase in response to phytohemagglutinin in patients and a 39% decrease in control subjects. Addition of indomethacin to phytohemagglutinin cultures increased the response of cells in patients with sarcoidosis by 192% +/- 32% versus a 112% +/- 18%-increase for control subjects (mean +/- SEM, P less than 0.05). Patients had an increased percentage of monocytes in peripheral blood mononuclear cell preparations, and the percent monocytes correlated with the percent increase in phytohemagglutinin response after glass wool passage (r = 0.62, P less than 0.05). Thus, several factors contribute to the depressed phytohemagglutinin response in sarcoidosis patients: an increased suppression by the prostaglandin-producing suppressor cell, an increased percentage of monocytes, and an as yet undefined factor.

Six patients are described in whom panniculitis was a major manifestation of systemic lupus erythematosus. These patients were seen in a combined-clinics population of 270 patients with systemic lupus erythematosus for an incidence of approximately 2%. Panniculitis was the first symptom of systemic lupus erythematosus in three of these patients indicating that systemic lupus erythematosus should be considered as an underlying cause in patients with panniculitis or Weber-Christian's disease. Analysis of these six cases and those previously reported suggests that the addition of hydroxychloroquine to the treatment regimen may be beneficial in lupus panniculitis.

Patients with active systemic lupus erythematosus (SLE) show significant reductions of T cells with receptors for the Fc portion of IgG, Tγ cells, which have been found to suppress in vitro B-cell responses to pokeweed mitogen. T cells with receptors for the Fc portion of IgM, Tμ cells, which show both helper and suppressor functions, are also reduced in SLE. Levels of both Tγ and Tμ cells in patients with inactive disease are intermediate between those of patients with active SLE and normal individuals. In a majority of individual patients, levels of Tγ cells were found to fluctuate with disease activity. SLE patients with reduced levels of Tγ cells showed high levels of circulating immune complexes, although a uniform inverse correlation was not detected. The pathophysiologic mechanisms in the observed decrease of T-cell subsets in SLE patients were studied by determination of the effect of aggregated IgG (an in vitro model of immune complexes) and lymphocytotoxic antibodies on T-cell subsets from normal individuals. Addition of aggregated IgG led to irreversible reduction of Tγ cells with no effect on Tμ cells. By contrast, both types of T-cell subsets were reversibly decreased by SLE sera with lymphocytotoxic antibody activity. Thus the observed decrease in T-cell subsets appears to be secondary to both immune complexes and lymphocytotoxic antibodies in SLE patients, and is reversible with remission of disease activity. Analysis of T-cell subpopulations in SLE appears to reflect other laboratory parameters associated with disease activity in these patients.

The Medical Research Education Subcommittee of the American Rheumatism Association surveyed a random selection of large and small programs in internal medicine and family practice residency programs in order to evaluate their rheumatology training. Formal rheumatology training is offered in 90% of these residency programs, but many available positions are not being filled. A full-time staff rheumatologist was present at 69% of large internal medicine programs, 32% of small internal medicine programs, and 11% of family practice programs. The methods of rheumatology training are similar in most programs, although small internal medicine programs and family practice programs more often utilize physicians' offices or outside medical centers for the rheumatology elective training. A majority of the directors of these residency programs thought that many basic skills and techniques were not taught adequately and that the training of their rheumatology residents was not equal to that of residents in cardiology or gastroenterology.

We encountered an unusual case of arthritis caused by Serratia marcescens , with both positive and negative birefringent crystals in the same inflammatory synovial fluid. This combination of events is most likely to occur in men over 40 years old who have a predisposing illness or are receiving immunosuppressive drugs. This case shows the need to consider multiple pathological processes occurring in the same joint. ( Arch Intern Med 136:1323-1325, 1976)

The prevalence of lymphocytotoxic antibody was studied in 131 relatives of 10 patients with Hodgkin's disease. The study group contained nine families, five of which had two subjects with Hodgkin's disease. One hundred twenty-eight control family members were studied in parallel. Lymphocytotoxic antibody was present in 35.5% of all family members of patients with Hodgkin's disease, and in 8.6% of controls (P less than 0.01). Lymphocytotoxic antibody appeared primarily in consanguineous relatives irrespective of close personal household contact with the probands. The prevalence of the antibody was equal in both first- and second-degree relatives. These findings suggest at least a genetic and possibly an environmental influence in the genesis of lymphocytotoxic antibody among relatives of patients with Hodgkin's disease.

Lung tissues from patients with rheumatoid arthritis and pulmonary involvement were studied with direct immunofluorescence. Immunofluorescence was carried out with conjugated antisera to γM, γG, γA, and β1C, as well as direct staining for rheumatoid factor with conjugated aggregates of γG globulin. Striking immunofluorescence was recorded with conjugated anti-γM and conjugated heat aggregated γ-globulin to localize tissue deposition of γM rheumatoid factor. Patchy fluorescence of γG was also noted. No specific fluorescence for γA or β1C was found. Positive lupus erythematosus (LE) cell preparations and serum levels of intermediate γG complexes (11-15S) were found in a large proportion of the patients, although no correlation with the clinical or pathologic processes could be established. It is postulated that rheumatoid factor plays an intrinsic role in the pathogenesis of the lesions found in rheumatoid lung disease.