Khader N. Mustafa

Ocrelizumab: a step forward in the evolution of B-cell therapy

Recent advances in our understanding of B-cell dysregulation and its important link to autoimmunity have brought about a radical change in the management of autoimmune diseases. Over the past few years, encouraging data from several clinical trials of rituximab, a chimeric anti-CD20 antibody, have led to its approval for use in rheumatoid arthritis (RA). These data, regarding clinical efficacy, safety, improved patient-reported outcomes and cost-effectiveness with the use of rituximab in patients with RA, have led to the exploration of other agents targeting B-cell functions. Ocrelizumab, a novel humanized anti-CD20 antibody, has shown clinical efficacy and safety in a recently reported trial in patients with RA. Future clinical trials will help evaluate further the role of ocrelizumab in RA and its potential use in other autoimmune diseases. This review describes current understanding of B-cell therapy, the role of rituximab in the treatment of RA and the evolving role of ocrelizumab as a B-cell-targeted therapy.

HLA-B27 Prevalence in Arab Populations and Among Patients with Ankylosing Spondylitis

Objective. To investigate prevalence of HLA-B27 among general Arab populations and among patients with ankylosing spondylitis (AS), and to review published data. Methods. The prevalence of HLA-B27 was studied among 2579 unrelated healthy Jordanians, almost equally divided among Palestinian refugees and natives of Jordan, reflecting the general population of Jordan. The prevalence of HLA-B27 was also studied among 129 patients with AS, 70 from Jordan, and the remaining 59 from Qatar. HLA typing was performed by standard 2-stage micro-lymphocytotoxicity method. We also reviewed published English language studies of HLA-B27 in Arab patients with AS and general populations retrieved through Medline and cross-reference search. Results. We observed that the general prevalence of HLA-B27 among Jordanians is 2.4%; while the reported prevalence ranges between 2% and 5% among major Arab populations. The prevalence of HLA-B27 among patients with AS is 71% in Jordan and 73% in Qatar, while the reported prevalence from pooled published data from various Arab populations is 64%. Conclusion. From these data one can conclude that HLA-B27 is present in about 2% to 5% among major Arab populations and that its prevalence in Arab patients with AS is closer to 70%.

Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients.

OBJECTIVES Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1 (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study was to find out if there is an association between those polymorphisms and MTX toxicity and/or response in Jordanian RA patients. METHOD A genotyping approach was used to determine the studied polymorphisms in 159 RA patients. RESULTS There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX toxicity. Patients with RFC1 80GG genotype were at higher risk for gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T variant allele were at higher risk for MTX overall toxicity (p = 0.04), especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A polymorphism between males and females was significantly different. The variant genotype 80AA was found to be more in males than in females (60% vs. 31%) (p = 0.011). CONCLUSIONS Our results suggest that genetic polymorphisms in methotrexate transporters affect the toxicity but not the response of MTX treatment. Further studies should be performed to have more conclusive results.

Polyarthritis with chondronecrosis associated with osteonecrosis, panniculitis and pancreatitis

Arthritis associated with panniculitis complicating pancreatitis is well described in the literature, usually associated with osteonecrosis. Chondronecrosis has not been reported before in association with pancreatitis. We report a patient with chronic pancreatitis who presented with polyarthritis, panniculitis, osteonecrosis, but in addition had clear evidence of chondronecrosis. We suggest that direct extension of noxious materials from nearby subchondral osteonecrotic bone lesion could be the cause of the osteonecrosis and one of the pathological mechanisms leading to arthritis in patients with pancreatitis.

Musculoskeletal disorders of the hand in type 2 diabetes mellitus: prevalence and its associated factors.

To assess the prevalence of musculoskeletal disorders of the hand among adult patients with type 2 diabetes mellitus (T2DM) and their relation to disease duration, glycemic control and microvascular complications.

N-acetyltransferase-2 genotypes among patients with rheumatoid arthritis attending Jordan University Hospital.

AIM To determine the frequency of major N-acetyltransferase (NAT2) alleles and genotypes among Jordanian patients with rheumatoid arthritis (RA). METHODS The study was approved by the IRB of the Jordan University Hospital. An informed consent was signed by every patient. DNA samples from 150 healthy volunteers and 108 patients with RA were analyzed by polymerase chain reaction followed by a restriction fragment length polymorphism assay (PCR-RFLP) to determine the frequency of four major alleles: NAT2*4, NAT2*5, NAT2*6, and NAT2*7. RESULTS The most prevalent genotypes are those that encode the slow acetylation phenotype. About 59.3% of the patients with RA carried the slow, 33.3% the intermediate, and 7.4% the fast-encoding genotypes. The frequency of NAT2 alleles was 0.241 (95% confidence interval [CI] 0.184-0.298) for NAT2*4, 0.449 (95% CI 0.383-0.515) for NAT2*5, 0.273 (95% CI 0.214-0.332) for NAT2*6, and 0.037 (95% CI 0.012-0.062) for NAT2*7 allele. The overall frequency of the slow acetylation genotype in patients with RA is similar to that in healthy Jordanian volunteers. However, the NAT2*5/7 genotype was found in seven patients (6.5%) with RA and was absent in Jordanian volunteers, and the z test revealed that the difference was statistically significant. This genotype constituted 10.9% of the genotypes encoding slow acetylation. CONCLUSION The overall acetylator genotype in RA is similar to that in healthy volunteers. The overall slow acetylator genotypes do not seem to be a genetic risk factor for RA among Jordanians. However, the NAT2*5/7 genotype seems to be related to RA. The nature of this relationship needs further clarification.

Validation of the Arabic version of the revised Fibromyalgia Impact Questionnaire (FIQR_A) on Jordanian females with fibromyalgia

The aim of this study was to translate and validate the Arabic version of the Revised Fibromyalgia Impact Questionnaire (FIQR_A). Translation of the FIQR followed a worldwide-recognized approach to ensure the accuracy and equivalency of the translation from the English version of the FIQR. Following the translation of the FIQR, 92 women with fibromyalgia completed the FIQR_A, the Arabic Research ANd Development Short Form Health Survey (RAND SF-36), and the Arabic Hospital Anxiety and Depression Scales (HADS). The FIQR_A significantly correlated with RAND SF-36 domains and HADS. The correlations ranged from fair to moderate. For selected outcomes, Bland–Altman plots were consistent with Spearman’s correlations. Test–retest intraclass correlation coefficients were all significant and ranged from moderate to excellent. Internal consistency was found to be excellent. These observations suggest that the FIQR_A is a valid and reliable tool for both clinical practice and research purposes with Arabic speakers globally.

Thiopurine S-methytransferase Gene Polymorphism in Rheumatoid Arthritis

BACKGROUND AND AIMS Thiopurine S-methyltransferase (TPMT) is responsible for inactivation of thiopurine drugs which are commonly used in leukemia, organ transplantation and autoimmune diseases. The gene encoding TPMT is polymorphic, and both phenotyping and genotyping studies have shown ethnic variations in gene sequence and enzyme activity worldwide. The aim of this study is to identify the most common genetic polymorphisms of TPMT in healthy Jordanian volunteers and patients with rheumatoid arthritis (RA). METHODS A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to identify the frequency of TPMT (*2, *3A, *3B, and *3C) polymorphisms in 250 healthy Jordanian volunteers and 110 RA patients. RESULTS Only four healthy subjects (1.6%) and one RA patient (0.9%) with variant alleles were identified in this study. Two healthy subjects had the TPMT*3A allele and the other two had the TPMT*3B allele, whereas the one RA patient had the TPMT*3A allele. No homozygous polymorphisms were detected and all genotypes detected were heterozygous (*1/*3A) (*1/*3B). None of the subjects had TPMT*2 or TPMT*3C variant alleles. CONCLUSIONS Mutant alleles identified in this study have a low frequency. TPMT (*3A and *3B) were the only detected heterozygous alleles. No homozygous variant allele was detected. Further studies are necessary to identify other variant alleles that might uniquely occur in Jordanians.