Management of Peripheral Arthritis in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: We aimed to compile evidence for the efficacy and safety of therapeutic options for the peripheral arthritis domain of psoriatic arthritis (PsA) for the revised 2021 Group in Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations. METHODS: A working group consisting of clinicians and patient research partners was convened. We reviewed the evidence from new randomized controlled trials (RCTs) for PsA treatment from February 19, 2013, to August 28, 2020. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-informed approach to derive evidence for the classes of therapeutic options for 3 patient groups: (1) naïve to treatment, (2) inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and (3) inadequate response to biologic DMARDs (bDMARDs). Recommendations were derived through consensus meetings. RESULTS: The evidence review included 69 RCTs. We derived GRADE evidence for each class of therapeutic options and achieved consensus for the recommendations. For patients naïve to treatment, the working group strongly recommends csDMARDs (methotrexate, sulfasalazine, leflunomide) and phosphodiesterase 4 inhibitors, and emphasizes regular assessment and early escalation to achieve treatment target. bDMARDs (tumor necrosis factor inhibitors [TNFi], interleukin 17 inhibitors [IL-17i], IL-12/23i, IL-23i) and Janus kinase inhibitors (JAKi) are also strongly recommended. For patients with inadequate response to csDMARDs, we strongly recommend TNFi, IL-17i, IL-12/23i, IL-23i, and JAKi. For those who had prior experience with bDMARDs, we strongly recommend a second TNFi, IL-17i, IL-23i, and JAKi. The evidence supporting nonpharmacological interventions was very low. An expert panel conditionally recommends adequate physical activity, smoking cessation, and diet to control weight gain. CONCLUSION: Evidence supporting optimal therapy for the peripheral arthritis domain of PsA was compiled for the revised 2021 GRAPPA treatment recommendations.

Two-Year Safety and Effectiveness of Peficitinib in Moderate-To-Severe Rheumatoid Arthritis: A Phase IIb, Open-Label Extension Study.

INTRODUCTION: Peficitinib is a novel orally bioavailable, once-daily Janus kinase (JAK) inhibitor approved in Japan for the treatment of rheumatoid arthritis (RA). This 2-year extension study of two global phase IIb trials investigated the long-term safety and effectiveness of peficitinib. METHODS: All eligible patients with moderate-to-severe RA including patients in the placebo group who participated in one of two global phase IIb trials ('with methotrexate' or 'without methotrexate') were included in this 2-year open-label extension study and were converted to peficitinib 100 mg once daily. The primary objective was to evaluate an additional 2 years of safety by assessing treatment-emergent adverse events (AEs) and clinical laboratory evaluations for 105 weeks. Evaluation of an additional 2 years of effectiveness using American College of Rheumatology (ACR) 20/50/70 responses was the exploratory objective. RESULTS: Overall, 611 patients were enrolled in the extension study: 319 (52.2%) patients completed the study and 292 (48%) discontinued treatment, including for withdrawal of patient consent (n = 96), failure to achieve low disease activity (n = 62), and AE not including death (n = 41). AEs were reported in 463 (76%) patients. The most common AEs (per 100 patient-years) were upper respiratory tract infections (9.9) and urinary tract infections (7.2). Serious AEs were reported in 80 (13%) patients, with incidences per 100 patient-years of serious infections 2.7, herpes zoster 1.5 (including one herpes zoster ophthalmic), and malignancies 0.6 (most frequently basal cell carcinoma). At week 105, 269 (44%) patients demonstrated an ACR20 response relative to their respective phase IIb trial baselines. CONCLUSION: Among 319 patients who completed this 2-year extension of two global phase IIb studies, peficitinib 100 mg once daily demonstrated a stable safety profile and sustained effectiveness in patients with moderate-to-severe RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01711814. Registered 19 October 2012. FUNDING: Astellas Pharma Global Development, Inc.

Targeted drugs in spondyloarthritis during pregnancy and lactation.

Spondyloarthritis (SpA) are a heterogeneous group of chronic inflammatory joint diseases that includes several clinical subgroups. SpA can affect women in the reproductive stage so pregnancy can influence the course of the disease and SpA can affect the maternal-fetal outcome. The treatment of SpA has changed dramatically in recent years and the use of targeted drugs is part of therapeutic armamentarium. The use of targeted drugs during pregnancy is controversial because the information available on safety during this period is still limited. Several cytokines have an important role in the normal development of pregnancy or other cytokines may play a role in certain maternal-fetal complications. Potentially targeted drugs can affect the function of these cytokines during pregnancy. The aim of this study is to review the interrelationship between SpA during pregnancy and lactation, the role of some cytokines during normal pregnancy and the development of maternal-fetal complications as well as to review recent information on targeted drugs during pregnancy and breastfeeding in these patients in order to maximize their use in these critical periods of life.

Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and -173 G>C): association with MIF and TNFα in psoriatic arthritis.

Psoriatic arthritis (PsA) is an autoimmune disease with a complex interaction of gene and with a dysregulation of pro-inflammatory cytokine such as Macrophage migration Inhibitory Factor (MIF) and Tumor Necrosis Factor-alpha (TNFα). Two polymorphisms identified in the promoter region of the MIF gene have been described: the STR-794 CATT5-8 (rs5844572) and the SNP-173 G>C (rs755622), which are associated with increased MIF levels in circulation and with autoimmune diseases in several populations. In this case-control study we investigated whether commonly occurring functional MIF polymorphisms are associated with PsA susceptibility and clinical variables as well as with MIF and TNFα serum levels in a Mexican-Mestizo population. Genotyping of the -794 CATT5-8 and -173 G>C MIF polymorphisms was performed by PCR and PCR-RFLP respectively in 50 PsA patients and 100 healthy subjects (HS). MIF and TNFα serum levels were determined by ELISA. A significant increase of MIF (PsA: 7.8 vs. HS: 5.25 ng/mL; p < 0.001) and TNFα (PsA: 24.6 vs. HS: 9.9 pg/mL; p < 0.001) levels was found in PsA patients, a significant correlation was observed between MIF and TNFα (r = 0.41; p < 0.01). The 5,6 repeats genotype of the -794 CATT5-8 MIF was associated with protection to PsA (OR = 0.29; CI 0.77-0.98; p = 0.03), and the G/C genotype (OR = 7.5; CI 2.92-21.64; p < 0.001) and the -173*C allele (OR = 2.45; CI 1.43-4.20; p < 0.001) of the -173 G>C MIF were associated with susceptibility to PsA. In conclusion the -173*C allele is associated with susceptibility to PsA in Mexican-Mestizo population, whereas the correlation between MIF and TNFα soluble levels provided evidence that both cytokines are closely related in the pathophysiology of the PsA.

Tophus burden reduction with pegloticase: results from phase 3 randomized trials and open-label extension in patients with chronic gout refractory to conventional therapy.

INTRODUCTION: Two replicate randomized, placebo-controlled six-month trials (RCTs) and an open-label treatment extension (OLE) comprised the pegloticase development program in patients with gout refractory to conventional therapy. In the RCTs, approximately 40% of patients treated with the approved dose saw complete response (CR) of at least one tophus. Here we describe the temporal course of tophus resolution, total tophus burden in patients with multiple tophi, tophus size at baseline, and the relationship between tophus response and urate-lowering efficacy. METHODS: Baseline subcutaneous tophi were analyzed quantitatively using computer-assisted digital images in patients receiving pegloticase (8 mg biweekly or monthly) or placebo in the RCTs, and pegloticase in the OLE. Tophus response, a secondary endpoint in the trials, was evaluated two ways. Overall tophus CR was the proportion of patients achieving a best response of CR (without any new/enlarging tophi) and target tophus complete response (TT-CR) was the proportion of all tophi with CR. RESULTS: Among 212 patients randomized in the RCTs, 155 (73%) had ≥ 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45% of patients in the biweekly group (P = 0.002 versus placebo), 26% in the monthly group, and 8% in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28%, 19%, and 2% of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54% vs 20%, respectively and 8% with placebo). CONCLUSIONS: Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy. TRIAL REGISTRATIONS: NCT00325195, NCT01356498.

Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.

CONTEXT: Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. OBJECTIVE: To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. DESIGN, SETTING, AND PATIENTS: Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. INTERVENTION: Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). MAIN OUTCOME MEASURE: Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. RESULTS: In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). CONCLUSION: Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00325195.

Increased CD28 serum levels are not associated with specific clinical activity in systemic lupus erythematosus.

CD28 is one of the main activator receptors involved in systemic lupus erythematosus (SLE) pathogenesis, and its expression and serum levels are significantly higher in patients with SLE and other autoimmune diseases than in healthy controls (HC). However, it is unknown whether this increase is associated with specific organ damage. Therefore, our objective was to measure the CD28 levels in serum from SLE and HC groups to confirm the CD28 serum levels increase, as reported previously, and to determine whether this increase was associated with specific organ activity and the SLE Disease Activity Index (SLEDAI). Forty SLE patients and 40 matched HC were included, and the age, disease duration, SLEDAI and Mexican SLEDAI were recorded for the SLE group. CD28 serum levels were measured by ELISA. There was a statistically significant increase in the CD28 serum levels of SLE patients compared to controls (p = 0.039); however, we did not find any significant correlation with disease activity indices or organ involvement, although we found a significant but low correlation with C3. Our results and a review of the literature suggest that the increase in CD28 serum levels may be the result of CD28 gene overexpression, which could be related to the decrease in CD28+ T cells, T-cell hyporesponsiveness and immune impairment that occurs in SLE.

FCGR3A V(176) polymorphism for systemic lupus erythematosus susceptibility in Mexican population.

The objective of this study is to establish whether there is an association between the presence of FCGR3A V(176) polymorphism with SLE or its manifestations. We included 94 patients according to the 1982 ACR criteria as well as 98 controls matched by age and gender. The 11 ACR diagnostic criteria were analyzed on the clinical files. The polymorphism FCGR3A V(176) was determined by direct sequencing. There was not an association between the polymorphism FCGR3A V(176) with SLE or its main manifestations. The allelic frequency for F(176) was: 0.80 and 0.72 in cases and controls, respectively (P = 0.09, IC95%: 0.42-1.07); and the genotypic frequency in the group of cases was: 0.65 for homozygotes F(176)/F(176), 0.30 for heterozygotes and 0.05 for the homozygotes V(176)/V(176), while for the control group it was 0.53, 0.39 and 0.08, respectively. The polymorphism FCGR3A V(176) is not associated with SLE or any of its manifestations in patients with SLE from the West of Mexico.

Manifestaciones oculares en artritis reumatoide juvenil / Juvenile rheumatoid arthritis and ocular manifestations

La artritis reumatoide juvenile (ARJ) es considerada como la enfermedad del tejido conectivo más frecuente en la infancia. La incidencia de manifestaciones oculares, es variable y ha sido reportado entre 5 y 24 por ciento. La iridociclitis que se desarrolla en los pacientes con ARJ, es la alteración más grave y puede llevar a los niños a la pérdida total de la visión. El objetivo de este estudio fue conocer la frecuencia y tipo de manifestaciones oculares en pacientes con ARJ en nuestro medio. Se realizó un estudio descriptivo y trasversal. Se analizaron 30 pacientes con diagnóstico de ARJ con edad promedio de inicio de 10.2 años (2-5 años), evaluación promedio de la enfermedad de 4.6 años (3 meses-35 años). En este estudio la frecuencia de alteraciones oculares fue de 40 por ciento (12 pacientes). Sin embargo, no todas las alteraciones encontradas se asociarion a la presencia de ARJ. La queratoconjuntivitis sieca se presentó en el 23 por ciento (7 pacientes) y en ningún caso se detectó iridociclitis aguda o crónica. La presencia de daño ocular en estos pacientes pudiera depender de otros factores (genéticos, ambientales, etc.) aunque la evaluación periódica no detecte patología grave; se pueden encontrar alteraciones menos mediante vigilancia y seguimiento oportunos

Prolapso de la válvula mitral en pacientes con espondilitis anquilosante: estudio prospectivo

La espondilitis anquilosante (EA) es una enfermedad sistémica que puede cursar con manifestaciones en diversos órganos o sistemas. Se han identificado problemas cardiovasculares, principalmente lesiones valvulares, aortitis o pericarditis así como defectos de conducción. En este trabajo, se estudian las manifestaciones cardiovasculares en 15 pacientes adultos con diagnóstico de EA por medio de métodos precisos en cuanto a la función y estado anatómico cardiovascular y aórtico. Se encontró problema en 4 pacientes, 2 con prolapso de valva posterior de la válvula mitral, uno con insuficiencia aórtica y otro con dilatación de la aorta. A los dos pacientes con prolopso valvular no se les había detectado problema clínicamente ni por electrocardiografía. A un grupo de 13 pacientes tomados como control, con diagnóstico de artritis reumatoide con edad similar y el mismo protocolo basado en evaluación clínica por cardiólogo, radiografía P.A. de tórax, electrocardiograma convencional en todas las derivaciones y ecocardiograma no se le encontró ninguna lesión similar