The Long-Term Effects of Short-Period Adalimumab Biosimilar Usage in Ankylosing Spondylitis.

Background Cost and drug toxicity frequently deter the long-term use of anti-tumor necrosis factor (TNF) agents in ankylosing spondylitis (AS). Therefore, this study was conducted to observe long-term relief after the short-term administration of an anti-TNF agent. Methodology A one-year, prospective, interventional, uncontrolled, single-center trial was conducted. There were 50 patients with symptomatic active chronic AS who received rheumatology therapy and were anti-TNF naive. Every two weeks, 40 mg of standard biosimilar adalimumab (Bs-ADA, Exemptia™) was administered subcutaneously for six injections (10 weeks) or to continue with standard follow-up if they did not achieve an Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) index response by week 12. Standard indicators (Assessment Spondyloarthritis International Society/ASAS and Bath) were used to evaluate progress. In addition, TNF-alpha, interleukin (IL)-6, and IL-17 were tested using a commercially available enzyme-linked immunosorbent assay kit from Bio Legend (Bengaluru, India). Results Patients experienced early and significant improvement in pain, non-steroidal anti-inflammatory drugs (NSAIDs) requirement, function, and several indices (ASAS 20 and 40, ASAS partial remission, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score) after discontinuing injections. At weeks 12 and 48, 84% and 52% of patients showed ASAS 20 improvement, with 34% and 24% showing ASAS partial remission. Over half of the patients continued to improve and provided proof of concept. Conclusions In difficult-to-treat AS, a 10-week course of biosimilar adalimumab demonstrated significant early improvement that often lasted for 24 weeks. This unconventional method proved to be economically appealing. It merits further confirmation and acceptance, especially in resource-constrained contexts.

Effectiveness of chloroquine and inflammatory cytokine response in patients with early persistent musculoskeletal pain and arthritis following chikungunya virus infection.

OBJECTIVE: To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection. METHODS: During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/IgG anti-CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24-week, 2-arm, parallel efficacy trial of CQ (250 mg/day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin-6 [IL-6], interferon-γ [IFNγ], tumor necrosis factor α, CXCL10/IFNγ-inducible protein 10, and IL-13). Twenty-two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent-to-treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched. RESULTS: There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain -3.9 and -4.2, respectively). Patients improved significantly. Cytokine levels remained several-fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent. CONCLUSION: This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status.

Pain and disability, perceptions and beliefs of a rural Indian population: A WHO-ILAR COPCORD study. WHO-International League of Associations for Rheumatology. Community Oriented Program for Control of Rheumatic Diseases.

OBJECTIVE: The WHO-ILAR Community Oriented Program for Control of Rheumatic Diseases (COPCORD) primarily aims to estimate the burden of rheumatic-musculoskeletal symptoms/disorders (RMS). We investigated data on pain and disability, perceptions and beliefs in the first rural community based COPCORD study in India. METHODS: A total of 4092 adults were interviewed (response rate 89%) in a population survey (Stage 1) in Bhigwan village in 1996 using modified COPCORD core questionnaires. Twenty-one trained volunteers completed the survey in 5 weeks. Those reporting RMS were identified (Phase 1) to complete a self-evaluation questionnaire (Phase 2) prior to rheumatological evaluation (Phase 3). Phase 2 included questions on perceptions and beliefs regarding pain, effect on life, work and socioeconomic factors, disability, and therapy; only the moderate and severe grades were considered significant. Patients marked their pain sites on a manikin during the presurvey week. A validated modified Health Assessment Questionnaire disability index (HAQDI) in the local language evaluated functional disability. RESULTS: RMS were the predominant ailments reported by 746 adult villagers (18.2%; 95% CI 17.1, 19.2). Moderate pain of > 2 years' duration was reported by almost 60% of RMS patients. Neck (6%), lumbar (11.4%), shoulder (7.4%), elbow (6.5%), wrist (6.4%), hand (6.1%), knee (13.2%), calf (6.6%), and ankle (6.5%) were the common painful sites, predominantly in women; 91%, 89%, and 31% with RMS reported a significant grade of pain, RMS illness, and disturbed sleep, respectively. In the age group 25-54 years, 21% of those with RMS perceived a significant effect on work ability, while less than 20% of those with RMS admitted a similar effect on their personal life (including finances). About 10% with RMS had ceased to work because of RMS. Among RMS subjects 21% scored a significant HAQDI, but many more reported significant difficulty (HAQ) in the individual items of walking, hygiene (squatting), arising (from sitting cross-legged), reaching, and occupational/household chores; this corresponded to the dominant pain sites in low back and lower limbs. Oral tobacco use was reported to be significantly greater (p < 0.001) in the RMS patients. Past trauma was recalled by 23% of patients, and many connected this to their RMS. Modern medicines were consumed by 55% of patients with RMS. Among patients, 86% and 65% expected "pain relief" and "cure," respectively, from their doctor; 23% of patients wanted greater sympathy and attention. However, 21% of patients had never visited a doctor and were only identified by the COPCORD study. CONCLUSION: The findings of this study (1) demonstrate that RMS, although a predominant ailment, has a modest effect on daily living in most subjects with RMS; (2) indicate there is inconsistency between the measures of pain and disability (using HAQ) and their effects; (3) describe the beliefs and expectations of the community. Based on the data and community support, the COPCORD has been continued for Stages II and III, especially with a view to health education.