Leflunomide is equally efficacious and safe compared to low dose rituximab in refractory rheumatoid arthritis given in combination with methotrexate: results from a randomized double blind controlled clinical trial.

BACKGROUND: The standard dose of rituximab used in rheumatoid arthritis (RA) is 1000 mg but recent studies have shown that low dose (500 mg) is also effective. Efficacy of low dose rituximab in rheumatoid arthritis (RA) refractory to first-line non-biologic Disease Modifying Anti Rheumatic Drugs (DMARDs), compared to leflunomide is unknown. In a tertiary care referral setting, we conducted a randomized, double blind controlled clinical trial comparing the efficacy and safety of low-dose rituximab-methotrexate combination with leflunomide-methotrexate combination. METHODS: Patients on methotrexate (10-20 mg/week) with a Disease Activity Score (DAS) > 3.2 were randomly assigned to rituximab (500 mg on days 1 and 15) or leflunomide (10-20 mg/day). The primary end-point was ACR20 at 24 weeks. Sample of 40 had 70% power to detect a 30% difference. ACR50, ACR70, DAS, EULAR good response, CD3 + (T cell), CD19 + (B cell) and CD19 + CD27+ (memory B cell) counts, tetanus and pneumococcal antibody levels were secondary end points. RESULTS: Baseline characteristics were comparable in the two groups. At week 24, ACR20 was 85% vs 84% (p = 0.93), ACR50 was 60% vs. 64% (p = 0.79) and ACR70 was 35% vs 32% (P = 0.84), in rituximab and in leflunomide groups respectively. Serious adverse events were similar. With rituximab there was significant reduction in B cells (p < 0.001), memory B cells (p < 0.001) and pneumococcal antibody levels (P < 0.05) without significant changes in T cells (p = 0.835) and tetanus antibody levels (p = 0.424) at 24 weeks. With leflunomide, significant reduction in memory B cells (p < 0.01) and pneumococcal antibody levels (p < 0.01) occurred without significant changes in B cells (P > 0.05), T cells (P > 0.05) or tetanus antibody levels (P > 0.05). CONCLUSIONS: Leflunomide-methotrexate combination is as efficacious as low-dose rituximab-methotrexate combination at 24 weeks, in RA patient's refractory to initial DMARDs. The high responses seen in both groups have favorable cost implications for patients in developing countries. Changes in immune parameters with leflunomide are novel and need further characterization. TRIAL REGISTRATION: The trial was registered with the Sri Lanka Clinical Trials Registry (SLCTR), a publicly accessible primary registry linked to the registry network of the International Clinical Trials Registry Platform of the WHO (WHO-ICTRP) (registration number: SLCTR/2008/008 dated 16th May 2008).

Chronic low back pain and its association with lumbar vertebrae and intervertebral disc changes in adults. A case control study.

AIM: This study was done to determine the association between chronic low back pain and vertebral fractures, intervertebral disc space (IDS) narrowing, vertebral osteophytes and spondylolisthesis among adults. METHOD: This case control study was done in Sri Lanka. Cases were patients with low back pain and controls were without low back pain. Postero-anterior and lateral radiographs of lumbar sacral spine of both groups were studied. To detect vertebral fractures in fourth and fifth lumbar vertebrae, anterior and posterior heights of vertebrae were measured using a Vernier caliper and antero-posterior ratio (A/P) was calculated. Having an A/P ratio value of < 0.89 was considered as a vertebral fracture. Presence of disc space narrowing, vertebral osteophytes and spondylolisthesis was assessed by two radiologists working independently. Bivariate and logistic regression analysis was done to find associations. RESULTS: There were 140 cases and 140 controls. Mean (SD) age for cases was 51.6 (17) years. Mean (SD) age for controls was 50 (15) years. Females made up 62% of cases and controls. Fifth lumbar vertebral fracture (odds ratio [OR] = 10.2; P = 0.001), fourth lumbar vertebral fracture (OR = 2.5; P = 0.017) and IDS narrowing (OR = 4.15, P = 0.009) had a significant association with low back pain and vertebral osteophytes and spondylolisthesis did not have a significant association with low back pain. CONCLUSION: Only vertebral fractures and IDS narrowing had a significant association with chronic low back pain.

Pregnancy outcomes and contraceptive use in patients with systemic lupus Erythematosus, rheumatoid arthritis and women without a chronic illness: a comparative study.

OBJECTIVES: To compare the pregnancy outcomes and contraceptive practices in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and women with no chronic illness (WNCI) in a tertiary care referral center in Colombo, Sri Lanka. METHODS: Patients with SLE satisfying American College of Rheumatology criteria for diagnosis and history of pregnancies were recruited from university lupus clinic, National Hospital of Sri Lanka (NHSL). Age-matched women with history of pregnancy and RA were recruited from the rheumatology clinic, NHSL and WNCI from a surgical clinic. RESULTS: In 71 patients with SLE, 79 pregnancies occurred in 38 patients. The number of total pregnancies in SLE, RA and WNCI (79, 80 and 85 respectively) were not significantly different (P > 0.05), but most occurred before diagnosis of SLE and RA. Pregnancies occurring after diagnosis were significantly higher in SLE compared to RA (P = 0.013, χ2 = 6.169). Mean age at diagnosis was higher (P < 0.01) in RA (35 years) than in SLE (26 years). Percentage live births after diagnosis was significantly lower (P < 0.01) in SLE (9/20; 45%) compared to RA (6/8; 75%) and WNCI (77/85; 91%). Adverse fetal outcomes (fetal loss, pre-maturity, low birth weight) and assisted deliveries were significantly more (P < 0.001) in SLE than in WNCI. Unplanned pregnancies were significantly higher (P < 0.01) in SLE (80%) compared to RA (25%) and in WNCI (9.4%). Contraceptive usage was lower in patients with SLE (25.6%) and RA (33%) compared to WNCI (56.4%). Disease exacerbations occurred in 20% of SLE patients during pregnancy. CONCLUSIONS: More pregnancies occur in SLE than in RA after diagnosis of illness. Unplanned pregnancies and adverse pregnancy outcomes need to be addressed more in SLE than in RA or in WNCI.