Background: Methotrexate (MTX) remains the most commonly prescribed drug used to treat rheumatoid arthritis (RA). Polymorphisms in solute carrier organic anion transporter family member 1B3 (SLCO1B3) and SLCO1B1 may play a critical role in MTX pharmacokinetics and patient outcomes. However, research on these polymorphisms in Saudi Arabia remains limited. We evaluated the association of SLCO1B3 (rs4149117, rs7311358) and SLCO1B1 (rs2306283, rs4149056) polymorphisms with MTX efficacy and safety in Saudi patients with RA. Methods: This multicenter, case-control study included patients diagnosed with RA in Jeddah and Taif. Demographic and clinical data were collected and analyzed. Genotyping of SLCO1B3 (rs4149117, rs7311358) and SLCO1B1 (rs2306283, rs4149056) polymorphisms was performed using Sanger sequencing. Statistical analyses, including logistic regression and haplotype analysis, were conducted to evaluate associations between these polymorphisms, MTX efficacy, and toxicity. Results: The study cohort comprised 100 patients with RA, with 46 showing a good response to MTX and 54 showing a poor response. Clinical predictors of MTX response were significantly higher in patients with poor response. Both SLCO1B3 polymorphisms (rs4149117, rs7311358) were significantly associated with anemia. Significant associations were found between SLCO1B1 (rs2306283) and gastrointestinal disturbances and anemia. The GAAT haplotype was significantly more prevalent among good responders, while the TGGT haplotype was significantly associated with poor responders. Conclusions: These results highlight the importance of genetic testing in predicting MTX treatment outcomes and tailoring personalized treatment plans for patients with RA to improve efficacy and minimize adverse effects.

Background/Objectives: Methotrexate (MTX) is currently the most widely used treatment for Rheumatoid Arthritis (RA) due to its demonstrated efficacy and well-known safety profile. However, the effectiveness and toxicity of MTX can vary among patients, partly due to genetic factors. Therefore, this study aimed to investigate the associations between the polymorphisms in the ABC subfamily G member 2 (ABCG2) gene and MTX effectiveness/toxicity in Saudi Arabia RA patients. Methods: The study is a retrospective, multicenter, case–control study that uses Sanger sequencing techniques for genotyping. Results: More than half of the patients (55.56%) were poor responders, with a slightly higher mean age. However, there was no significant difference between the two groups, not only in terms of age but also in other demographics and clinical factors. Regarding the rs2231137 polymorphism, the CC, CT, and TT genotype frequency were 91%, 7%, and 2%, respectively. The mutated variant (TT) was only observed in the positive rheumatoid factor group. Notably, none of these genotypes displayed any significant correlation with demographic characteristics, clinical features, or MTX efficacy/toxicity. Conclusions: This study is the first pharmacogenetic study of rs2231137 polymorphism in RA patients utilizing linear regression, revealing that rs2231137 polymorphism is not a predictor of either MTX efficacy or toxicity in RA patients. Therefore, more research is needed.

This work aimed to study neuropsychiatric (NP) events related to systemic lupus erythematosus (SLE) in an Asian African cosmopolitan cohort attending a tertiary care university hospital. Medical records of 312 adults with SLE were retrospectively revised. Patients’ from 14 Asian and 13 African countries were subgrouped according to the presence of NP manifestations. Electromyography and nerve conduction studies (EMG/NCS), electroencephalogram (EEG), computerized tomography and magnetic resonance imaging brain were considered. The systemic lupus international collaborating clinics damage index (SLICC-DI) was assessed. Patients were 275 females and 37 males (7.4:1), mean age 37.5 ± 12.7 years and disease duration 5.2 ± 3.2 years. 242 were Asian (150 Saudis) and 70 African. 279 were adult-onset, 26 juvenile-onset and 7 elderly-onset. NP manifestations were present in 48.4%. In NPSLE, magnetic resonance imaging brain showed white matter lesions (11.3%), infarction (9.9%), posterior reversible encephalopathy syndrome (5.2%),brain atrophy (1.3%) and vasculitis (2.6%); electromyography and nerve conduction studies revealed polyneuropathy (11.9%) and electroencephalogram epileptical changes in 3.3%. In NPSLE, lupus nephritis, receiving rituximab, SLICC-DI and mortality were significantly higher (53%, 16.6%, 1.94 ± 1.9 and 19.2% vs 36.6%, 8.1%, 0.54 ± 1.04 and 8.7%; P = .004, P = .02, P < .0001 and P = .008 respectively). NP manifestations were similar between Asians and Africans (47.1% vs 52.9%; P = .4). SLICC-DI was significantly lower in Saudis (0.88 ± 1.28) compared to non-Saudis (1.53 ± 1.91; P = .001). NP involvement is frequent in SLE patients especially females and is related to renal affection. Damage, mortality and receiving rituximab were significantly higher in those with NP manifestations. NP events are similar between Asian and African patients and damage in Saudis was remarkably less.