Alberto Berman

Rheumatic manifestations of human immunodeficiency virus infection

PURPOSE The prevalence and characteristics of the rheumatic and extra-rheumatic manifestations of human immunodeficiency virus (HIV) infection were determined in a prospective manner. PATIENTS AND METHODS One hundred one patients with HIV infection were consecutively interviewed and examined. The prevalence of autoantibodies and their association with rheumatologic symptoms were also determined. RESULTS The musculoskeletal system was involved in 72 patients. Thirty-five patients had arthralgias, 10 had Reiters syndrome, two had psoriatic arthritis, two had myositis, and one had vasculitis. Also found were two previously unreported syndromes. The first, occurring in 10 patients, consisted of severe intermittent pain involving less than four joints, without evidence of synovitis, of short duration (two to 24 hours), and requiring therapy (ranging from nonsteroidal antiinflammatory drugs to narcotics). The second, occurring in 12 patients, consisted of arthritis (oligoarticular in six patients, monoarticular in three patients, and polyarticular in three patients) involving the lower extremities and lasting from one week to six months. The synovial fluid of five patients (three with arthritis, one with Reiters syndrome, and one with psoriatic arthritis) was sterile and inflammatory. CONCLUSION Musculoskeletal complications are common in advanced stages of HIV infection. Persons in a high-risk group for HIV infection who manifest oligoarthritis with or without any other extra-articular manifestation suggestive of Reiters syndrome or other form of spondyloarthropathy should be tested for HIV.

A Phase II Randomized Study of Subcutaneous Ixekizumab, an Anti–Interleukin‐17 Monoclonal Antibody, in Rheumatoid Arthritis Patients Who Were Naive to Biologic Agents or Had an Inadequate Response to Tumor Necrosis Factor Inhibitors

To evaluate ixekizumab, an anti–interleukin‐17A (anti–IL‐17A) monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients: biologics‐naive patients and patients with an inadequate response to tumor necrosis factor (TNF) inhibitors.

Double-blinded infliximab dose escalation in patients with rheumatoid arthritis.

Objective: To determine the efficacy, safety and pharmacokinetics of infliximab dose escalation in patients with rheumatoid arthritis (RA) who had an inadequate response to 3 mg/kg infliximab treatment or whose disease flared after initially responding. Methods: Patients with active RA, despite receiving methotrexate, received infliximab 3 mg/kg at weeks 0, 2, 6 and 14 in one of the three arms of the START trial. Beginning at week 22, patients had their infliximab dose increased in a double-blind fashion in increments of 1.5 mg/kg if the total tender and swollen joint count did not improve by at least 20% from baseline (lack of response) or the improvement at week 22 or later worsened by 50% or more (criterion for flare). Results: Of the 329 evaluable patients, 100 (30.4%) patients required dose escalation at or after week 22 because of flare or lack of response. The majority of patients (>80%) who received up to three dose escalations showed ⩾20% improvement in the total tender and swollen joint count after their last dose escalation. Patients who required dose escalations generally had lower preinfusion serum infliximab concentrations than those who did not require them. The incidences of adverse events and serious adverse events for the patients who received dose escalation(s) were similar to those of patients who did not receive dose escalation. Conclusion: Fewer than one-third of patients required a dose escalation. The majority of patients showed improvement after receiving increased doses of infliximab, without an increased risk of adverse events.

Clinical response and tolerability to abatacept in patients with rheumatoid arthritis previously treated with infliximab or abatacept: open-label extension of the ATTEST Study

Objective To assess the efficacy and safety of abatacept in biological-naive patients with rheumatoid arthritis and an inadequate response to methotrexate treated in the long-term extension (LTE) of the ATTEST trial. Methods Patients randomly assigned to abatacept, placebo or infliximab completing the 1-year double-blind period were eligible to receive abatacept ∼10 mg/kg in the open-label LTE. Efficacy to year 2 is presented for patients randomly assigned to abatacept or infliximab who switched to open-label abatacept. Safety data are presented for all patients entering LTE regardless of double-blind treatment. Results Of 431 patients randomly assigned, 79.8% remained on abatacept at year 2. At years 1 and 2, 19.7% and 26.1% of abatacept and 13.3% and 28.6% of infliximab-to-abatacept patients achieved disease activity score 28-defined remission (<2.6). Safety with abatacept during the cumulative study period was consistent with the double-blind experience, with no increase in adverse event incidence following the switch to abatacept. Conclusion In methotrexate-inadequate responders, abatacept efficacy was maintained over 2 years. For infliximab-to-abatacept patients, efficacy improvements were seen in year 2 after patients switched to abatacept. Switching directly from infliximab to abatacept was well tolerated. These data demonstrate that abatacept provides sustained responses and consistent safety, suggesting that switching from infliximab to abatacept is a viable treatment option.

The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a Phase IIb Study of Adults With Active Psoriatic Arthritis.

To evaluate the efficacy of clazakizumab, a monoclonal antibody with high affinity and specificity for the interleukin‐6 (IL‐6) cytokine, in psoriatic arthritis (PsA).

Differential Features Between Primary Ankylosing Spondylitis and Spondylitis Associated with Psoriasis and Inflammatory Bowel Disease

Objective. To describe differential characteristics of axial involvement in ankylosing spondylitis (AS) as compared with that seen in psoriatic arthritis (PsA) and inflammatory bowel disease (IBD) in a cohort of Ibero-American patients. Methods. This study included 2044 consecutive patients with spondyloarthritis (SpA; ESSG criteria). Demographic, clinical, disease activity, functional ability, quality of life, work status, radiologic, and therapeutic data were evaluated and collected by RESPONDIA members from different Ibero-American countries between June and December 2006. Patients selected for analysis met modified New York criteria (mNY) for AS. Results. A total of 1264 patients met the New York criteria for AS: 1072 had primary AS, 147 had psoriatic, and 45 had IBD-associated spondylitis. Median disease duration was comparable among the 3 patient groups. Patients with primary AS were significantly younger (p = 0.01) and presented a higher frequency of males (p = 0.01) than the other 2 groups. Axial manifestations such as inflammatory back pain and sacroiliac pain were significantly more frequent in patients with primary AS (p = 0.05) versus other groups, whereas frequency of dactylitis, enthesitis, and peripheral arthritis was more common in patients with psoriatic spondylitis (p = 0.05). Spinal mobility was significantly more limited in patients with primary AS versus the other 2 groups (p = 0.0001). Radiologic changes according to BASRI total score were equally significant in primary AS. Disease activity (BASDAI), functional ability (BASFI), and quality of life (ASQoL) scores were comparable in the 3 groups. Conclusion. Patients with primary AS had more severe axial involvement than those with spondylitis associated with psoriasis or IBD. Functional capacity, disease activity, and quality of life were comparable among the groups studied.

The Efficacy and Safety of Subcutaneous Clazakizumab in Patients With Moderate-to-Severe Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results From a Multinational, Phase IIb, Randomized, Double-Blind, Placebo/Active-Controlled, Dose-Ranging Study

Clazakizumab is a humanized monoclonal antibody that binds to the interleukin‐6 (IL‐6) cytokine. This study was undertaken to evaluate the efficacy and safety of clazakizumab in combination with methotrexate (MTX) or clazakizumab monotherapy versus MTX alone in patients with rheumatoid arthritis (RA) and an inadequate response to MTX.

OP0021 A phase 2 study of multiple subcutaneous doses of LY2439821, an anti-IL-17 monoclonal antibody, in patients with rheumatoid arthritis in two populations: Naïve to biologic therapy or inadequate responders to tumor necrosis factor alpha inhibitors

Background IL-17A (IL-17) is a potential therapeutic target for rheumatoid arthritis (RA) therapy. Objectives To evaluate an anti-IL-17 monoclonal antibody, LY2439821 (LY), for safety and efficacy in 2 populations: naïve to biologic therapy (bDMARD naïve) or inadequate responders to tumor necrosis factor (TNF-IR). Methods In this randomized, double-blind study, 260 bDMARD naïve patients (pts) received subcutaneous placebo (PB) or LY (3, 10, 30, 80, or 180 mg) and 188 TNF-IR pts received PB or LY (80 or 180 mg) at Weeks 0, 1, 2, 4, 6, 8, and 10 with concomitant DMARD therapy. The objectives were to determine the dose-response relationship of LY in bDMARD naïve pts based on the ACR20 response rate (primary) by logistic regression at Week 12, and to evaluate efficacy and safety (secondary). Results There was a significant dose response relationship in bDMARD naive pts at week 12 (p=0.031 using ACR20; p<0.001 using DAS28-CRP). Significant differences vs. PB were seen for DAS-28 CRP reductions in bDMARD naïve pts and in TNF-IR pts at all LY doses, with a rapid onset of efficacy within 1 week after the first dose and with increasing magnitude of reductions with increasing doses (Figure). In both populations, significant differences vs PB were observed for other clinical measures. The frequency of treatment-emergent adverse events (TEAEs) was similar across treatment arms (range: 45-64%). Infections were more frequent in LY arms combined compared to PB in bDMARD naïve (25 vs 19%) and TNF-IR pts (27 vs 23%) with no observed dose relationship. In bDMARD naive pts, SAEs occurred in 1 (2%) PB and 7 (3%) LY pts (6 treatment emergent) with 1 serious infection-related event in a pt receiving LY 80 mg. In the TNF-IR population, SAEs occurred in 1 (2%) PB pt and 12 (10%) LY pts (10 treatment emergent), and serious infections occurred in 4 (3%) pts in LY arms combined. Conclusions LY significantly improved signs and symptoms of RA compared to PB with the best evidence of dose response seen using the DAS-28. The safety profile was comparable to other biologic therapies with no unexpected safety concerns. Disclosure of Interest M. Genovese Grant/Research support from: Eli Lilly and Company, Consultant for: Eli Lilly and Company, M. Greenwald Grant/Research support from: Eli Lilly and Company, C.-S. Cho Grant/Research support from: Eli Lilly and Company, A. Berman Grant/Research support from: Eli Lilly and Company, L. Jin Employee of: Eli Lilly and Company, G. Cameron Employee of: Eli Lilly and Company, L. Wang Consultant for: Pharmanet/I3, L. Xie Employee of: Eli Lilly and Company, D. Braun Employee of: Eli Lilly and Company, P.-Y. Berclaz Employee of: Eli Lilly and Company, S. Banerjee Employee of: Eli Lilly and Company

Gender differences among patients with primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease in an iberoamerican spondyloarthritis cohort.

AbstractThe aim of the study was to compare clinical manifestations, disease activity, functional capacity, spinal mobility, and radiological findings between men and women from a multicenter, multiethnic Ibero-American cohort of patients with Spondyloarthritis (SpA).This observational cross-section study included 1264 consecutive SpA patients who fulfilled the modified New York criteria for ankylosing spondylitis (AS). Demographic, clinical, and radiologic data were evaluated. Categorical data were compared by X2 or Fishers exact tests and continuous variables by ANOVA with post-hoc tests.Primary AS was diagnosed in 1072 patients, psoriatic spondylitis in 147, and spondylitis associated to inflammatory bowel disease (IBD) in 45 patients. Overall, male patients were significantly younger, had longer diagnostic delay, lower disease activity, worse spinal mobility, better quality of life, and more severe radiologic damage. Dactylitis and enthesitis, as well as swollen joint count, were significantly more common among women. In primary AS, there was a marked male predominance (76.2%). Among patients with psoriatic spondylitis, male predominance was lower (57.8%), but was also associated with worse spinal mobility and more severe radiologic damage. In the total population, male patients with primary AS referred higher permanent work disability (13.2% vs 6.9%; P < 0.05), although no difference was observed in psoriatic or IBD spondylitis according to the gender.Among Ibero-American SpA patients, there are some differences in clinical and radiological manifestations, men showing more structural damage, whereas women more active disease. These data suggest that the phenotype of SpA differs between genders. This can influence the subsequent diagnostic approach and therapeutic decisions.

Classification systems for human immunodeficiency virus (HIV) infection.

Excerpt To the editor: Several classification systems based on clinical and immunologic profiles have been proposed for patients infected with the human immunodeficiency virus (HIV) (1, 2). A singl...