Neutrophile to lymphocyte and platelet to lymphocyte ratios predict clinical response to bDMARD in naïve spondylarthritis patients.

Objective: We aim to study association between neutrophile to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios and disease activity, and their value to predict bDMARD response. Methods: A set of spondylarthritis (SpA) patients under bDMARD registered in the Reuma.pt registry was studied. Sociodemographic, clinical and laboratorial variables were assessed on bDMARD initiation, 6, 12, 18 and 24 months (M) thereafter. Univariable and multivariable generalized estimation equations models assessed associations with disease activity. The NLR and PLR predictive value was assessed using univariable and multivariable logistic regression models. Results: A total of 170 patients were included. Most were male (54.7%), with a predominantly axial phenotype (84.7%). Significant associations were observed between NLR [B=1.55, 95% confidence interval (CI) = (1.38; 1.74)] and PLR [(B=1.16, 95% CI = (1.09; 1.24)] with ASDAS-CRP (p < 0.001). Both baseline ratios predicted ∆ ASDAS-CRP ≥ 1.1 at 6 months [OR = 2.20, 95% CI = (1.21, 4.00) for NLR; OR = 1.02, 95% CI = (1.01, 1.04) for PLR, p < 0.01)]. PLR was a significant predictor of ∆ ASDAS-CRP ≥ 1.1 in all timepoints [OR (12 M) = 1.02, 95% CI = (1.00, 1.03), p < 0.05; OR (18M) = 1.02, 95% CI = (1.01, 1.03), p < 0.001; OR (24M) = 1.01, 95% CI = (1.01, 1.02), p < 0.01]. Conclusion: NLR and PLR were associated with disease activity during the follow up of these patients. They seem to be significant predictors of therapeutic response to bDMARD in naïve SpA patients.

Anakinra and hepatotoxicity in pediatric rheumatology: a case series.

BACKGROUND: Anakinra is a recombinant interleukin-1 (IL-1) receptor antagonist used in systemic juvenile idiopathic arthritis (sJIA), refractory Kawasaki disease (KD) and cryopyrin-associated autoinflammatory syndrome (CAPS). Anakinra associated hepatotoxicity, while rare, has been described in several cases in daily practice. ​In this case series the authors describe three pediatric patients with this side effect in the setting of severe macrophage activation syndrome (MAS) in KD and sJIA. CASE PRESENTATION: The first patient was a 12-year-old boy who presented with fever, maculo-papular exanthema and polyarthralgia. Tonsillitis, distal limb induration and tender cervical lymph nodes were observed. Erythrocyte-sedimentation rate (ESR), C-reactive protein (CRP), ferritin (11,975 ng/mL), D-dimers (5,98 mg/L FEU) and soluble CD25 (3645 pg/mL) levels were elevated. Exclusion of sepsis / toxic shock syndrome warranted introduction of IV methylprednisolone and immunoglobulin (IG IV), with partial response. A MAS secondary to KD was assumed, and anakinra 2 mg/kg/day was introduced. Twenty days later he developed new-onset nausea and severe cyto-cholestasis, normalizing after 2 months of drug discontinuation. Posterior onset of polyarthritis and evanescent lead to a final diagnosis of sJIA. The second patient was a 2-year-old boy with a 10-day history of fevers, generalized rash, hepatosplenomegaly and strawberry tongue. Leucocytosis with neutrophilia and elevated CRP were observed. Initial treatment with IVIG in the setting of incomplete KD was ineffective. Mild anaemia, leukopenia and very high serum ferritin (maximum 26,128 ng/mL) ensued. Presumptive sJIA associated MAS was treated with IV methylprednisolone and anakinra 2 mg/kg/day, with prompt response. Four weeks later transaminitis was detected, and temporary anakinra suspension led to normalisation of laboratorial values. The third case related to a 4-year-old boy presenting with fever, maculopapular rash and cervical lymphadenopathy. CRP and ESR were elevated, and KD was diagnosed. IVIG and methylprednisolone were initiated with clinical worsening, warranting for anakinra introduction at 2 mg/kg/day. After three weeks, liver enzymes progressively elevated, resolving on 2 weeks of anakinra discontinuation. CONCLUSIONS: To the best of our knowledge, this is the first case series describing anakinra associated hepatotoxicity in pediatric patients with rheumatic diseases other than sJIA, bringing additional insight to therapeutic monitoring in patients undergoing this treatment.

Immune-mediated skin lesions related to biological disease-modifying antirheumatic drugs: a 22-year experience of a tertiary center.

INTRODUCTION: Immune-mediated skin lesions (IMSL) can be very disabling leading to treatment discontinuation. Although these lesions have rarely been previously described, the true incidence is unknown. OBJECTIVE: To explore the cumulative incidence, management and outcomes of IMSL related to bDMARD in a large cohort of patients with chronic inflammatory rheumatic diseases. To explore possible associations and risk factors for IMSL development. METHODS: A retrospective single-center study of patients with rheumatoid arthritis (RA), spondylarthritis (SpA) and psoriatic arthritis (PsA) that had been treated with at least one bDMARD for at least 6 months was conducted. IMSL related to bDMARD characteristics and outcomes were collected. RESULTS: A total of 989 patients with RA, SpA and PsA were included. Twenty-seven patients (2.7%) presented IMSL potentially related to bDMARD, being psoriasis the most common IMSL (n=12, 44.4%), followed by drug-induced lupus erythematosus (n=6), alopecia areata (n=3) and leukocytoclastic vasculitis (n=2). IMSL led to withdrawal of bDMARD in 18 of the 27 patients (66.7%). Patients with IMSL had younger age at diagnosis (p=0.038), longer disease duration (p=0.018), longer duration of bDMARD treatment (p=0.008), and higher number of previous bDMARDs (p < 0.001) than patients without IMSL. In the group of patients with IMSL there was a significantly higher percentage of patients treated with adalimumab (p < 0.001). In multivariate regression model, the number of previous bDMARDs (OR 2.13, 95%CI 1.47-3.10, p < 0.001) and treatment with adalimumab (OR 4.60, 95%CI 1.96-10.80 , p < 0.001) were statistically significant predictive factors for IMSL development. CONCLUSION: In our study, IMSL related to bDMARDs had an estimated cumulative incidence of 2.7%. Younger age at diagnosis, longer disease duration, longer duration of bDMARD treatment, higher number of previous bDMARDs and treatment with adalimumab were independently associated with an increased risk of IMSL development.

The impact of antinuclear antibodies seroconversion induced by anti-tumor necrosis factor α agents on the clinical outcomes in rheumatic patients.

INTRODUCTION: Anti-tumor necrosis factor α (anti-TNFα) agents can potentially induce the anti-nuclear antibodies (ANA) development over time. Evidence of the real impact of these autoantibodies on clinical response to treatment in rheumatic patients is still scarce. OBJECTIVES: To explore the impact of ANA seroconversion induced by anti-TNFα therapy on clinical outcomes in biologic-naïve patients with Rheumatoid arthritis (RA), axial spondylarthritis (axSpA) and psoriatic arthritis (PsA). METHODS: An observational retrospective cohort study enrolling biologic-naïve patients with RA, axSpA and PsA who started their first anti-TNFα agent was conducted for 24 months(M). Sociodemographic data, laboratory findings, disease activity and physical function scores were collected at baseline, 12M and 24M. To examine the differences between the groups with and without ANA seroconversion, independent samples t-tests, Mann-Whitney U-tests and chi-square tests were performed. Linear and logistic regression models were used to assess the effects of ANA seroconversion on the clinical response to treatment. RESULTS: A total of 432 patients with RA (N=185), axSpA (N=171) and PsA (N=66) were included. ANA seroconversion rate at 24M was 34.6%, 64.3% and 63.6% for RA, axSpA and PsA, respectively. Regarding sociodemographic and clinical data in RA and PsA patients, no statistically significant differences between groups with and without ANA seroconversion were found. In axSpA patients, ANA seroconversion was more frequent in patients with higher body mass index (p=0.017) and significantly less frequent in patients treated with etanercept (p=0.01). Regarding disease activity, DAS28 for RA patients and ASDAS-CRP for axSpA patients were significantly higher in ANA seroconversion group at 12M (p=0.017 and p=0.009, respectively). For PsA patients, CDAI was significantly higher in ANA seroconversion group at 24M (p=0.043). Overall switching rate of biologic disease-modifying antirheumatic drugs (bDMARD) was significantly higher in the ANA seroconversion group over time (p=0.025). For RA patients, ANA seroconversion predicted DAS28 (ß=-0.21, 95%CI[-1.86;-0.18], p=0.017) at 12M. CONCLUSIONS: ANA seroconversion induced by anti-TNFα agents could interfere in clinical response of patients with rheumatic diseases. The presence of these autoantibodies can be considered as a potential predictor of poor treatment response and higher need for bDMARD switching over time.

Pulmonary sarcoidosis and immune-mediated necrotizing myopathy: an uncommon coincidence.

INTRODUCTION: Immune-mediated necrotizing myopathy (IMNM) is characterized by acute or subacute, severe proximal muscle weakness and myofiber necrosis with minimal inflammatory cell infiltrate observed on muscle biopsy. On the other hand, sarcoidosis is characterised by the presence of non-caseating granulomas that can develop in several organs. CASE REPORT: We present the unique case of a 49-year-old woman, with no previous medical history, who had a rare concomitant occurrence of IMNM and pulmonary sarcoidosis. This condition was successfully treated with a combination of corticosteroids and rituximab along with rehabilitation program. DISCUSSION: This association has been reported in only two previous case reports. This highlights the importance of further research on the connection between sarcoidosis and other forms of inflammatory myopathies.

Pseudo-pseudo Meigs syndrome: an uncommon onset of Systemic Lupus Erythematosus.

Serositis is seen in approximately 12% of patients with systemic lupus erythematosus (SLE), usually in the form of pleuritis or pericarditis. Peritoneal serositis with ascites is an extremely rare manifestation of SLE and ascites as initial manifestation of SLE is even rarer. Here, we describe a previously healthy 48-year-old female with periumbilical abdominal pain, constitutional symptoms, ascites, pleural effusions and raised CA-125 level as an initial manifestation of SLE, which led up to the diagnosis of pseudo-pseudo Meigs syndrome. PPMS is a rare manifestation of SLE and awareness of this entity among clinicians is crucial to ensure an early recognition and prompt treatment.

Effectiveness and safety of original and biosimilar etanercept (Enbrel® vs Benepali®) in bDMARD-naïve patients in a real-world cohort of Portugal.

OBJECTIVE: To compare the effectiveness and safety of original (Enbrel®) and biosimilar (Benepali®) etanercept in Biologic Disease-modifying Antirheumatic Drug (bDMARD)-naïve patients, measured by persistence rates over 36 months of follow-up. METHODS: A retrospective multicentre observational study using data collected prospectively from The Rheumatic Diseases Portuguese Registry (Reuma.pt) was performed, including patients with: age ≥ 18 years old; diagnosis of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Spondyloarthritis (SpA) (axial or peripheral) with active disease and biologic-naïve who initiated treatment with etanercept as the first line biological treatment after 2010. Kaplan-Meyer and Cox regression were used to calculate the persistence rate in treatment. Disease activity at baseline and follow-up data at 6, 12, 18 and 24 months of treatment were compared. Causes for discontinuing therapy were summarized using descriptive statistics. Statistical significance was assumed for 2-sided p-values <0.05. RESULTS: We included 1693 patients (413 on Benepali® and 1280 on Enbrel®): 864 diagnosed with RA, 335 with PsA and 494 with SpA. The 3-year persistence rates were not significantly different between both treatment groups in RA, PsA and SpA patients. In the adjusted Cox model, hazard ratios of discontinuation were not statistically different (p>0.05). The proportion of subjects in remission or low disease activity in each disease was similar in both groups. Overall, 535 (31.6%) patients discontinued etanercept (428 patients on Enbrel® and 107 patients on Benepali®). The major cause of discontinuation was inefficacy (57.8%). No differences for the occurrence of inefficacy or adverse effects were found between treatment groups. CONCLUSIONS: Benepali® and Enbrel® demonstrated similar effectiveness and safety in RA, PsA and SpA in our cohort of patients. These data corroborate that the original and biosimilar drugs have similar quality characteristics and biological activity.