ObjectiveTo evaluate the efficacy and safety of the immunotherapeutic vaccine interferon-α kinoid (IFN-K) in a 36-week (W) phase IIb, randomised, double-blind, placebo (PBO)-controlled trial in adults with active systemic lupus erythematosus (SLE) despite standard of care.MethodsPatients with SLE (185) with moderate to severe disease activity and positive interferon (IFN) gene signature were randomised to receive IFN-K or PBO intramuscular injections (days 0, 7 and 28 and W12 and W24). Coprimary endpoints at W36 were neutralisation of IFN gene signature and the BILAG-Based Composite Lupus Assessment (BICLA) modified by mandatory corticosteroid (CS) tapering.ResultsIFN-K induced neutralising anti-IFN-α2b serum antibodies in 91% of treated patients and reduced the IFN gene signature (p<0.0001). Modified BICLA responses at W36 did not statistically differ between IFN-K (41%) and PBO (34%). Trends on Systemic Lupus Erythematosus Responder Index-4, including steroid tapering at W36, favoured the IFN-K and became significant (p<0.05) in analyses restricted to patients who developed neutralising anti-IFN-α2b antibodies. Attainment of lupus low disease activity state (LLDAS) at W36 discriminated the two groups in favour of IFN-K (53% vs 30%, p=0.0022). A significant CS sparing effect of IFN-K was observed from W28 onwards, with a 24% prednisone daily dose reduction at W36 in IFN-K compared with PBO (p=0.0097). The safety profile of IFN-K was acceptable.ConclusionsIFN-K induced neutralising anti-IFN-α2b antibodies and significantly reduced the IFN gene signature with an acceptable safety profile. Although the clinical coprimary endpoint was not met, relevant secondary endpoints were achieved in the IFN-K group, including attainment of LLDAS and steroid tapering.Trial registration numberNCT02665364.

BackgroundThe immunotherapeutic vaccine Interferon--kinoid (IFN-K) consists of a heterocomplex of inactivated recombinant human IFN-2b coupled to a T-helper carrier protein, Keyhole Limpet Haemocyanin. A phase I/IIa was published. Here, we report the results of a 36 week (w) phase 2b, randomized, double-blind, placebo-controlled (PBO), multi-center study assessing the efficacy and safety of IFN-K in patients with active SLE on standard of care therapy.MethodsSLE patients (4 ACR criteria) with moderate to severe disease activity (SLEDAI 2K 6 and 1 BILAG A and/or 2 BILAG B scores); positive IFN gene signature; and ANA and/or anti-dsDNA, were randomized (1:1) to 5 IM injections of IFN-K or PBO at days 0, 7, 28, and months 3 and 6. Co-primary objectives at w36 were neutralization of IFN gene signature and BICLA response modified by mandatory corticosteroid (CS) tapering (5 mg/d prednisolone equivalent) by w24 with no increase to w36. Secondary objectives at w36 were SRI(4) and SRI(4) with CS tapering (5 mg or 7.5 mg/d prednisolone equivalent) by w36, Lupus Low Disease Activity State (LLDAS), safety and immunogenicity.ResultsAmong 185 patients randomized, 91 and 93 were respectively treated with IFN-K and PBO, and 85 (92.4%) and 84 (90.3%) completed the study. Seventy-two of 79 (91.1%) IFN-K treated patients (Per Protocol Set) developed anti-IFN neutralizing antibodies (Abs). Primary and secondary outcome measures at w36 are detailed in the Table:IFN-K was well tolerated, with similar rates of treatment-emergent adverse events (TEAEs 82.4% vs 76.3%) and TEAEs leading to study drug discontinuation (4.4% vs. 4.3%) in the IFN-K and PBO groups, respectively. Serious adverse events (SAEs) were more common on PBO vs IFN-K (12.9% vs 6.6%). Cancer (n=4) and lupus nephritis (n=2) were reported in the PBO group and there was one severe infection in the IFN-K group. One death occurred in each group.Abstract 198 Table 1 IFN-K Placebo p value IFN gene signature reduction−31.3%−0.4%<0.0001Modified BICLA 35 (41.2%)29 (34.5%)0.33SRI(4) 57 (67.9%)54 (65.1%)0.62SRI(4) with CS≤5 mg/d 43 (54.4%)30 (39%)0.07SRI(4) with CS≤5 mg/d (IFN-K subgroup with neutralizing Abs)40 (55.6%)30 (39.0%)0.04SRI(4) with CS≤7.5 mg/d 46 (58.2%)33 (42.9%)0.07SRI(4) with CS≤7.5 mg/d (IFN-K subgroup with neutralizing Abs)43 (59.7%)33 (42.9%)0.04LLDAS 45 (52.9%)25 (29.8%)0.002Mean CS dose *5.4 mg/d7.1 mg/d0.009*The mean daily CS dose was lower in the IFN-K group from w28 onwards.ConclusionsIFN-K induced neutralizing anti-IFN Abs in 91.1% of treated patients and significantly reduced IFN gene signature. Modified BICLA at w36 did not differ between IFN-K and PBO. Trends on SRI (4) with steroid tapering at w36 favored IFN-K, and became significant when patients exhibiting neutralizing Abs were included in the exploratory analysis. Furthermore achieving a Lupus Low Disease Activity State discriminated the two groups at w36, in favor of IFN-K. A significant CS sparing effect of IFN-K was observed from w28 onwards. The safety profile of IFN-K was acceptable. Results...

Background Sarcopenia refers to age-related loss of muscle mass and function. However, autoimmune sarcopenia refers to excessive weight loss usually with disproportionate muscle wasting due to cytokine excess. Previous studies have found a frequency of autoimmune sarcopenia of about 15 to 20%. The progressive loss of muscle mass lead to decrease in physical activity and a rise in cardiovascular and metabolic disorders. There is currently no widely accepted definition of sarcopenia in autoimmune diseases. Objectives The purpose of this study was to determine the frequency of muscle wasting in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods In a cross-sectional study, we screened the patients from outpatient clinic in the rheumatology service and were excluded patients with chronic disorders of heart, kidney and liver, also the patients that were on HMG-CoA reductase inhibitors treatment; we performed medical history and physical examination, specialist in clinical nutrition made the anthropometric measures, blood samples were taken for clinical laboratory analysis. Activity scales for each disease were made, DAS-28 in RA and MEX-SLEDAI in SLE patients. We determined the whole body lean mass using Dual-emission X-ray Absorptiometry (DEXA). Statistical analysis was performed using arithmetic mean, standard deviation, Student T test; chi-square and Fisher exact test when appropriate and Spearman rank correlation test all using SPSS program (v 12.0). Results Forty-six patients with autoimmune disease (AID), twenty six patients with RA and 20 with SLE according to the 1987 ACR criteria and 25 healthy subjects were analyzed; mean age of AID was 40±13.4 vs. 39±18 years in control group. Ninety-four percent were women. 90% of the AID group was taking hydroxychloroquine and 80% was on mild doses of corticosteroids. The anthropometric measures revealed obesity in 28% of the patients vs 16% in control group. The frequency of sarcopenia in AID group was 26% (12 pts) vs 20% (5 pts) in control group, p=0.000; There was no difference in the cases of sarcopenic-obesity. The risk of sarcopenia in sedentary patients was OR 1.93 (IC 95% 0.385 to 9.7). There was no correlation between activity scales of AID and sarcopenia rho =0.121 for SLE and rho=0.170 in RA patients. The use of hydroxychloroquine is not protection for muscle wasting OR 1.4 (IC 95% 0.147 to 14.59). Finally the risk of sarcopenia in patients with AID was OR 1.4 (IC 95% 0.434 to 4.596). Conclusions Our work demonstrated that patients with AID have a slightly risk of sarcopenia when are compared to control group. This finding may affect the quality of life and promote the increasing of morbidity in such patients. References Santos MJ, Vinagre F, Canas Da silva J, Gil V, Fonseca JE. Body composition phenotypes in systemic lupus erythematosus and rheumatoid arthritis: a comparative of caucasian female patients. Clin Exp Rheum; 2011 29: 470-476 Disclosure of Interest None Declared

Background The occurrence of fibromyalgia (FM) with other rheumatologic diseases has been estimated with the following frequencies; Psoriatic arthritis 24%, rheumatoid arthritis 25%, systemic lupus erythematosus 30% and Chron’s disease 49%. The diagnosis of FM is essentially made on clinical data, with the presence of trigger points, sleep disorders, some dysautonomic findings and the lack of evidence of inflammatory or degenerative disease. The clinical syndrome of FM and the spondyloarthritis (SpA) share some signs and symptoms such as fatigue, lower back pain, unspecific urinary disorders and sleep disturbances. Objectives The purpose of this study was to determine the frequency of FM in patients with spondyloarthritis and to describe the clinical findings that are shared in both diseases. Methods Forty patients from the outpatient clinic in the Rheumatology service with spondyloarthritis according to ESSG classification criteria were included. We reviewed medical files; the clinical evaluation was done by two independent rheumatologists, clinical assessments included BASDAI and BASFI for SpA group and FIQ for FM patients. Current drug treatment, ESR, CRP, RF, HLA-B27 antigen were done. X ray of sacroiliac joints and lumbosacral were made in all patients. Statistical analysis on the program SPSS v 17, using arithmetic mean, standard deviation and correlation with Pearson’s test. Results Out of 40 patients, 90% (36/40) were women and 10% (4/40) men. The mean age was 48±9.7, all the patients had some kind of SpA and fifty-seven percent (23/40) had FM. Eighty percent (32/40) of the patients with diagnosis of undifferentiated SpA, ankylosing spondylitis in 7.5% (3/40) and psoriatic arthritis in 7.5% (3/40). ESR was abnormal in 47.5% (19/40), CRP abnormal in 15% (6/40). The clinical scales BASDAI and BASFI were abnormal in 75% and 37% respectively; the functional index questionnaire for FM was abnormal in 42%. The most frequent painful enthesis were as follow: first costochondral joint 72%, seventh costochondral joint 60%, medial condyle of femur 70% and plantar fascia 70%. The positive trigger points were: inter-transverse lower neck space C4-C5 and C5-C6 62%, second chondrocostal joint 67%; Knee medial fat pad proximal to the joint line 72% and gluteal at upper outer quadrant 72%. No statistical correlation between BASDAI and FIQ r =0.101. Conclusions In our work the frequency of FM in patients that are classified as SpA was fifty percent. We hypothesized that in some patients with SpA, the initial clinical picture could have been signs and symptoms of FM, because they share signs and symptoms. We suggest investigating specific clinical data, such achillea and plantar enthesitis, in patients that are classified as primary FM. References Azevedo V, Paiva E, Hiurko LR, Amorim R. Occurrence of fibromyalgia in patients with ankylosing spondylitis. Bras J Rheumatol 2010; 50 (6): 646-54 Disclosure of Interest None Declared

Background Systemic Lupus Erythematosus (SLE) is a prototype of autoimmune disease that is characterized by multisystem involvement and production of multiple auto-antibodies that underwent tissue deposition and cause chronic inflammation. Some studies have suggested that the lupus patients have and increased risk of malignancies such as lymphoma, sarcoma and breast cancer. The risk of cervical dysplasia or an abnormal pap smear in women with SLE seems to be increased but in our country there is scanty data about the frequency of cervical abnormalities. Objectives The purpose of this study was to determine the occurrence of cervical dysplasia and Pap smear abnormalities in patients with systemic lupus erythematosus. Methods Cross-sectional study was performed, 30 women with SLE, according to ACR criteria, were included and we compared them with eighty-three historical controls from de data base of gynecological department. The clinical activity of SLE was measured with MEX-SLEDAI. Pap smear was done in the two groups and the patients with suspicious lesions on the cervix underwent colposcopy and cervical biopsy. Statistics analysis was done by using arithmetic mean, standard deviation, Mann-Whitney U test for comparison of groups and multivariate logistic regression for correlation, chi-square and Exact Fisher test for categorical variables, the program we used was SPSS (v 12.0). Results The frequency of cervical dysplasia in the SLE group was 23% versus 10% in the control group; the risk of intraepithelial dysplasia for SLE patients was OR 2.85 (IC 95% 1.93 to 8.71). When we did adjusted multivariate analysis, no association was found between cervical dysplasia and age of beginning the sexual life, the number of sex partners, the time of evolution of the disease, the use of corticosteroids or the immunosuppressive drug therapy. No correlation with clinical activity of SLE and cervical dysplasia. In a sub-analysis the infection by human papillomavirus was more frequent in the SLE group, 30% vs 4%, but we did not identified more risk of cervical dysplasia in the former patients OR 0.88 (IC 95% 0.22 to 0.352) Conclusions This work demonstrated that patients with SLE have more risk of cervical dysplasia than general population; we suggest that the epidemiological surveillance of this group of patients should be more careful, with pap smear more early in life and probably every 6 months apart. References Klumb EM, Araujo ML Jr, Jesus GR, Santos DB, Oliveira AV, Albuquerque EM, Macedo JM. Is higher prevalence of cervical intraepithelial neoplasia in women with lupus due to immunossuppresion? J Clin rheumatol 2010 oct; 16 (7): 355. Disclosure of Interest None Declared