Khaldoon Alawneh

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.

Neutrophilic myositis as a manifestation of celiac disease: a case report

A 42-year-old white man presented with recurrent attacks of muscle pain and swelling. Clinically, he looked like he had severe pyogenic infection. He failed to respond to multiple courses of wide-spectrum antibiotics. Repeated cultures from muscle lesions and from the blood were negative. Hospital course was very hectic and life threatening at times. Upon further questioning, the patient gave a history of frequent loose-bowel movements for many years. A duodenal biopsy with villous blunting and positive antiglidin antibodies confirmed the diagnosis of celiac disease. The patient had complete recovery and remained in remission on a gluten-free diet.

The Clinical and Nonclinical Values of Nonexercise Estimation of Cardiovascular Endurance in Young Asymptomatic Individuals

Exercise testing is associated with barriers prevent using cardiovascular (CV) endurance (CVE) measure frequently. A recent nonexercise model (NM) is alleged to estimate CVE without exercise. This study examined CVE relationships, using the NM model, with measures of obesity, physical fitness (PF), blood glucose and lipid, and circulation in 188 asymptomatic young (18–40 years) adults. Estimated CVE correlated favorably with measures of PF (r = 0.4 − 0.5) including handgrip strength, distance in 6 munities walking test, and shoulder press, and leg extension strengths, obesity (r = 0.2 − 0.7) including % body fat, body water content, fat mass, muscle mass, BMI, waist and hip circumferences and waist/hip ratio, and circulation (r = 0.2 − 0.3) including blood pressures, blood flow, vascular resistance, and blood (r = 0.2 − 0.5) profile including glucose, total cholesterol, LDL-C, HDL-C, and triglycerides. Additionally, differences (P < 0.05) in examined measures were found between the high, average, and low estimated CVE groups. Obviously the majority of these measures are CV disease risk factors and metabolic syndrome components. These results enhance the NM scientific value, and thus, can be further used in clinical and nonclinical settings.

Vascular function and brain-derived neurotrophic factor: The functional capacity factor

Brain-derived neurotrophic factor (BDNF) is essential for neurocognitive function. This study aims at establishing a plausible link between level of serum BDNF, functional capacity (FC), and vascular function in 181 young (age 25.5±9.1 years old), apparently healthy adults. Fasting blood samples were drawn from participants’ antecubital veins into plain glass tubes while they were in a sitting position to evaluate serum BDNF using enzyme-linked immunosorbent assay (ELISA). Mercury-in-silastic strain-gauge plethysmography was used to determine arterial function indices, blood flow and vascular resistance at rest and following 5 minutes of arterial ischemia. The 6-minute walk distance (6MWD) test was used to determine FC, according to the American Thoracic Society Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories guidelines. It was conducted in an enclosed corridor on a flat surface with a circular track 33 meters long. The walking course was demarcated with bright colored cones. The 6MWD correlated with BDNF (r=0.3, p=0.000), as well as with forearm blood inflow (r=0.5, p=0.000) and vascular resistance (r = −0.4, p=0.000). Subsequent comparison showed that BDNF and blood inflow were greater (p<0.05) while vascular resistance was less (p<0.05) in participants who achieved a longer 6MWD. Similarly, BDNF correlated with forearm blood inflow (r=0.4, p=0.000) and vascular resistance (r = −0.4, p=0.000). Subsequent comparison showed improved vascular function (p<0.05) in the participants with greater BDNF. In conclusion, these findings might suggest that improved vascular function in individuals with greater FC is mediated, at least partially, by an enhanced serum BDNF level.

Challenges and opportunities in the early diagnosis and optimal management of rheumatoid arthritis in Africa and the Middle East

Early diagnosis and early initiation of disease‐modifying antirheumatic drug (DMARD) therapy slow the progression of joint damage and decrease the morbidity and mortality associated with rheumatoid arthritis (RA). According to the European League Against Rheumatism (EULAR) guidelines, treatment should be initiated with methotrexate and addition of biological DMARDs such as tumour necrosis factor (TNF) inhibitors should be considered for RA patients who respond insufficiently to methotrexate and/or other synthetic DMARDs and have poor prognostic factors. Africa and the Middle East is a large geographical region with varying treatment practices and standards of care in RA. Existing data show that patients with RA in the region are often diagnosed late, present with active disease and often do not receive DMARDs early in the course of the disease. In this review, we discuss the value of early diagnosis and remission‐targeted treatment for limiting joint damage and improving disease outcomes in RA, and the challenges in adopting these strategies in Africa and the Middle East. In addition, we propose an action plan to improve the overall long‐term outlook for RA patients in the region.

Anti-TNF therapy in Jordan: a focus on severe infections and tuberculosis.

Background A high rate of infection has been reported in patients receiving treatment with anti-tumor necrosis factor (anti-TNF). This study describes the rate of and risk factors for serious infections in patients receiving anti-TNF agents in Jordan. Methods This retrospective observational study was conducted at a large tertiary referral center in the north of Jordan. Between January 2006 and January 2012, 199 patients who received an anti-TNF agent (infliximab, adalimumab, or etanercept) were included. Patients received the anti-TNF treatment for rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, or other conditions. A serious infection was defined as any bacterial, viral, or fungal infection that required hospitalization, administration of appropriate intravenous antimicrobial therapy, and temporary withholding of anti-TNF treatment. Results The mean duration of anti-TNF treatment was 26.2 months. Steroids were used in 29.1% of patients, while 54.8% were given additional immunosuppressant therapy (methotrexate or azathioprine). Only one anti-TNF agent was given in 70.4% of patients, while 29.6% received different anti-TNF agents for the duration of treatment. Serious infections were documented in 39 patients (19.6%), including respiratory tract infections (41%), urinary tract infections (30.8%), and skin infections (20.5%), and extrapulmonary tuberculosis in three patients (7.7%). Exposure to more than one anti-TNF agent was the only factor associated with a significant increase in the rate of infection (relative risk 1.9, 95% confidence interval 1.06–4.0, P=0.03). Conclusion Serious infections, including tuberculosis, were a common problem in patients receiving anti-TNF agents, and exposure to more than one anti-TNF agent increased the risk of serious infection.

The effect of neutralizing antibodies on the sustainable efficacy of biologic therapies: what’s in it for African and Middle Eastern rheumatologists

Over the last decade, biologic therapeutic proteins have advanced the treatment of diseases such as rheumatoid arthritis (RA). Therapeutic antibodies such as infliximab, adalimumab, rituximab, tocilizumab, golimumab, certolizumab pegol, the receptor construct etanercept, and abatacept, an anticluster of differentiation (CD)80/anti-CD86 fusion protein, are used as treatment for RA and ankylosing spondylitis (AS). Infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept are inhibitors of tumor necrosis factor (TNF), a key regulator of inflammation. Left untreated, progression of rheumatic diseases due to inflammation can lead to irreversible joint damage and serious disability. One limitation for the use of therapeutic antibodies is immunogenicity, the induction of antibodies by the adaptive immune system in response to foreign substances. The development of antidrug antibodies (ADAs) has a varying impact on the clinical efficacy of biologic agents for the treatment of RA and AS, depending on whether the ADAs are neutralizing or non-neutralizing. Studies have indicated that neutralizing ADAs are associated with a reduced efficacy, decreased drug survival, increased instances of dose escalation, and adverse events. Comparison studies of anti-TNF biologics have demonstrated that each drug has a different sustained efficacy profile depending on immunogenicity. The purpose of this review is to provide rheumatologists with information regarding the effect of neutralizing antibodies on the sustainable efficacy of anti-TNF biologic therapies. This information will be of value to practicing rheumatologists in Africa and the Middle East who should take into account the potential for changes in the efficacy and safety of biologic therapies and closely monitor patients under their care.

Association between vitamin B12 level and anti-parietal cells and anti-intrinsic factor antibodies among adult Jordanian patients with Helicobacter pylori infection

OBJECTIVE Evaluate the association of Helicobacter pylori infection with anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) and their impact on vitamin B12 serum level. PATIENTS AND METHODS One hundred patients (M/F: 43/57; age 46.5±17.5 years) who underwent upper gastrointestinal endoscopy at King Abdullah University Hospital, Irbid, Jordan were enrolled in the study. The patients were grouped as H. pylori-infected (n=81) or H. pylori negative (n=19) by histopathological examination. Fasting serum vitamin B12 levels, anti-parietal cell antibodies and anti-intrinsic factor antibodies for patients and controls were determined. RESULTS Anti-parietal cell antibodies and anti-intrinsic factor antibodies were positive in 9.9% and 18.5% of H. pylori-positive patients respectively. None of the H. pylori negative subjects had anti-parietal cell antibodies or anti-intrinsic factor antibodies. Serum vitamin B12 level was lower in the H. pylori-infected patients (275±70.4pg/mL) than in controls (322.9±60.7pg/mL; p<0.05). H. pylori was positive in 94% of the low-vitamin B12 group compared with 64.6% of the normal-vitamin B12 group (p<0.5). CONCLUSION Patients with H. pylori infection are more likely to have anti-parietal cell antibodies and anti-intrinsic factor antibodies. There was an association between H. pylori infection and lower vitamin B12 levels. H. pylori infection might be a significant factor in the pathogenesis of autoimmune gastritis.

Rheumatoid arthritis in Jordan: a cross sectional study of disease severity and associated comorbidities

Treating rheumatoid arthritis (RA) to target is advocated using disease activity measures. The impact of RA on the general health status of affected patients in Jordan is not well described. This study reported the severity of RA in Jordan and its association with consequent disabilities and comorbidities. A cross-sectional, observational study was conducted at King Abdullah University Hospital in the north of Jordan. All patients who were diagnosed with RA were included. Patients’ demographics, comorbidities, disease activity score (DAS 28), and clinical disease activity index (CDAI) were collected. Both DAS 28 and CDAI were utilized to categorize RA disease activity. A total of 465 patients with RA were included: 82% were females; mean age ± standard deviation (SD) was 47.62±14.6 years; and mean disease duration ± SD was 6±4.45 years. The mean ± SD for the DAS 28 and CDAI was 5.1±1.5 and 23±14.2, respectively. According to the DAS 28, 51% of the patients were in the high disease activity category and only 5% were in remission. On the other hand, according to the CDAI, 44% were in the high disease activity category and only 1% were in remission. In Jordan, patients with RA have a high severe disease rate and a low remission rate. The disease is often progressive and associated with comorbidities that need to be managed.

Candida albicans-Induced Chronic Thrombocytopenic Purpura

We present 2 patients with chronic immune thrombocytopenic purpura (ITP) secondary to Candida albicans infection. Neither patient responded to standard ITP therapy including splenectomy. Appropriate antifungal treatment of the C. albicans infection was followed by sustained improvement in platelet count in both patients. To our knowledge, this is the first report of ITP in association with C. albicans infection.