Efficacy & safety of adalimumab biosimilar in axial spondyloarthritis: A retrospective study from a tertiary care centre in South India

Materials & Methods

This is a retrospective study conducted in the department of Clinical Immunology and Rheumatology, Nizams’ Institute of Medical Sciences, Hyderabad, Telangana, India a tertiary care centre done over three months in 2024. Ethics approval was obtained by the Institutional Ethics Committee of the Nizams’ Institute of Medical Sciences. Data were collected from medical records on patients aged above 18 yr with axial spondyloarthritis satisfying Assessment of spondyloarthritis international society (ASAS) classification criteria, having high disease activity (bath ankylosing spondylitis disease activity index or BASDAI >2.1) despite maximal tolerated doses of 2 courses of non-steroidal anti-inflammatory drugs (NSAIDs) given for at least 4 wk each and initiated on adalimumab biosimilar between January 2018 and October 2023; biologic experienced patients were also included. We only included patients who had records of swollen joint and tender joint count and BASDAI available at 0, 12 and 24 wk. Patients with non-compliance of more than two doses or incomplete follow up details were excluded.

Primary objective was to determine percentage of patients on adalimumab biosimilar attaining BASDAI50 response at 12 wks. BASDAI50 response is 50 per cent or more improvement from the patient’s baseline BASDAI score¹¹. Secondary objectives were to determine the proportion of subjects attaining BASDAI50 response at 24 weeks and a clinically meaningful change in BASDAI (i.e. change in BASDAI >1.1) at 12 and 24 wk.

All demographics and clinical, laboratory and radiological characteristics at presentation, initiation of adalimumab, and follow up visits were recorded. The visit at which adalimumab was started was considered baseline. Patients received 40 mg of adalimumab biosimilar subcutaneously every other week along with concomitant methotrexate (MTX) or sulfasalazine and/or NSAIDs as per the treating physician’s discretion. Viral markers (HIV, HbSAg and HCV) and screening for latent tuberculosis with Mantoux and/or QuantiFERON®-TB Gold In-Tube test and chest X Ray were done for all patients before starting adalimumab. Safety and tolerability data were based on adverse events recorded by the physician or patient from medical records.

Results

Ninety-six patients were included in the study; details are shown in table I. Close to one quarter of patients presented to us with poor functional class (class III or IV). Hip involvement was present in 50 patients (53%) and three had undergone total hip replacement before the initiation of adalimumab. Comorbidities included systemic hypertension (4%), diabetes mellitus (1%), hypothyroidism (1%), coronary artery disease (2%), previous pulmonary tuberculosis (4%) and renal disease (2%). In pre-biologic screening, latent tuberculosis was identified in 35 patients and all received two-drug (isoniazid, rifampicin) prophylaxis for three months. Viral screening for HIV, hepatitis B and C was negative in all patients.

Efficacy of adalimumab biosimilar

At initiation of adalimumab, mean swollen joint count was 1.18±1.6, mean tender joint count was 5.2±4.6 and mean BASDAI was 5.8±1.2. At week 12, mean swollen joint count was 0.2±0.7, mean tender joint count was 1.7±2.8 and mean BASDAI was 2.9±1.4. BASDAI-50 response was seen in 52/96 patients (54%) at week 12. A clinically meaningful difference in BASDAI of greater than 1.1 at 12 wk was achieved by 81 (84%) patients (Figure).

Close

Figure.

Trend of disease activity measures (BASDAI, swollen and tender joint count) over 24 wk in study cohort.

Export to PPT

In the study, complete follow-up data at 24 wk was only available for 64 of the 96 patients. For these 64 patients, disease activity was assessed. The mean swollen joint count was 0.1±0.5, the mean tender joint count was 0.6±2.1, and the mean BASDAI was 2.3±1.4. At 24 wk, 70 per cent of these patients (n=47) showed a BASDAI50 response. Additionally, a clinically meaningful difference in BASDAI of greater than 1.1 was achieved by 59 of the patients (92%). Disease activity measures at 52 weeks were available for 12 patients; in them the mean swollen joint count was 0, the mean tender joint count was 0.6±1.7, and the mean BASDAI was 1.84±1.4.

Discussion

This study evaluates the efficacy and safety of an adalimumab biosimilar in a cohort of South Indian patients with axial spondyloarthritis, who are predominantly rural or semi-urban, of lower socioeconomic status, reliant on government funding, and present with a high cumulative disease burden. The results indicate that adalimumab biosimilar is efficacious with 54 per cent of subjects achieving a BASDAI50 response and 87 per cent attaining a minimal clinically meaningful response of change in BASDAI >1.1 at 12 wk.

Our study’s patient demographics, with a mean age of 29 years and median illness duration of 6 years, are consistent with other Asian cohorts^9,10,12. This contrasts with studies of predominantly Caucasian populations, such as those by Heijde and Rudwaleit et al ^3,13, which reported a higher mean age (approx. 44 years) and longer median illness duration (10 years). The differences could be due to a higher proportion of juvenile-onset spondyloarthritis (SpA) in our cohort (28%) or a potential detection bias in resource-limited settings like ours that can lead to underrepresentation of patients with subtle symptoms, or genuine ethnic and racial disparities in disease onset and severity^14,15.

Adalimumab has consistently demonstrated efficacy across various manifestations of spondyloarthritis, as evidenced by numerous large-scale randomised controlled trials^3,4,12,13. Two prior post-marketing surveillance studies^9,10 from India evaluated the adalimumab biosimilar ZRC-3197 and reported high clinical responses, though their methodologies differed substantially from our study. Both Kapoor et al⁹ and Chopra et al¹⁰ restricted their cohorts to patients with radiographic axial SpA, former being registry data and the latter uncontrolled clinical trial, whereas our retrospective, single-centre cohort also included non-radiographic SpA, thereby capturing a broader disease spectrum¹⁶. Efficacy outcomes varied, with Kapoor et al⁹ reporting a striking 95 per cent BASDAI50 response at 24 wk and Chopra et al¹⁰ reporting an 82 per cent ASAS20 response at 12 wk. There was a rapid tapering of adalimumab dosing starting at 10 wk by Chopra et al and a shorter median disease duration, missed visits and doses in the Kapoor et al⁹ study. On the other hand, our results are similar to previous RCTs; such as van der Hejide et al³, who reported a 45.2 per cent BASDAI-50 response rate at week 12 among 121 patients, and Rudwaleit et al¹⁷, who found a 57 per cent response rate in a cohort of 1125 patients. We found a high prevalence of peripheral arthritis (78%) and radiographic hip involvement (53%) compared to other cohorts^18-21. This may be explained by the high number of patients with juvenile-onset SpA, which is known to be associated with severe hip involvement. Also, peripheral arthritis may accumulate over time; studies reporting prevalence at diagnosis may underestimate the true lifetime burden¹⁸. The significant use of conventional DMARDs in up to 70 per cent of subjects may be related to the above reasons. While minor side effects like injection site reactions and non-serious infections are not uncommon with adalimumab^3,4,12,17, none were reported in this study, likely due to a retrospective design and passive surveillance. Despite three months of prophylactic anti-tubercular therapy, two patients in the cohort with latent tuberculosis developed active TB after starting adalimumab. One patient had a history of pulmonary TB, and the other had a history of chronic steroid use; both are known risk factors for TB reactivation. This underscores the crucial importance of proactive screening and treatment of latent TB before beginning adalimumab therapy.

Strengths of this study include documenting adalimumab biosimilar efficacy in a resource-constrained setting among patients with longstanding axial disease, hip involvement, and peripheral arthritis. Limitations include its retrospective, single-centre design, lack of blinded assessments, and reliance on medical records, which may introduce information bias. To minimise bias, only patients compliant with treatment and with disease activity measures at 0, 12, and/or 24 wk were analysed, using consistent disease activity measures to reduce variability. Assessment of long-term efficacy and safety beyond 24 wk was limited due to dependence on State Government funding, usually approved for 3 to 6 months. Abrupt discontinuation upon fund exhaustion may have caused selection bias, likely including only responders able to afford prolonged treatment at 24 wk, potentially skewing results.

In conclusion, adalimumab biosimilars are an effective treatment for axial spondyloarthritis in high-disease-burden populations. This efficacy, comparable to originator biologics but at a lower cost, provides a strong economic and clinical justification for increased government funding in resource-limited settings. Public health policies must prioritise consistent and sustained funding to improve treatment adherence, prevent disease flares, and enhance the productivity and quality of life of those affected.