Safety and efficacy of Rituximab in ankylosing spondylitis- a prospective clinical study Chief investigator- Dr. Kripasindhu Gantait, Associate Professor Co-investigator- Dr. Shinjan Patra, 2nd year post graduate trainee Dept. of General Medicine

Background- Present treatment options Non-steroidal anti-inflammatory drugs TNF-alpha inhibitors (halting disease progression in 50% of the cases) Methotrexate and sulfasalazine.

Inflammatory pathology Mostly mono-nuclear cell infiltration along with T-cell & B-cell mediated pathology with abundant CD-20+ cells in the biopsy material from spinal specimens of AS. H.Appel, C. Loddenkemper, Z.Grozdanovic Et Al., “Correlation Of Histopathological Findings And Magnetic Resonance Imaging In The Spine Of Patients With Ankylosing Spondylitis,” Arthritis Research Andtherapy, Vol. 8, No. 5, Article R143, 2006

Why Rituximab? Monoclonal antibody against CD20+ cells. No such infusion related reaction reported. Not having the propensity to activate latent tuberculosis infection. Can be used in chronic virological condition

Aims and objectives To assess the safety and efficacy of rituximab infusion as the principal drug without any other past immunosuppressant’s therapy in diagnosed case of AS as per modified new york criteria.

Study procedure Subjects included in the study assessed for BASDAI, BASFI, BASMI scores, blood for complete hemogram, ESR, CRP, MRI of sacro-iliac joint, ASDAS-CRP score initially and follow them up on 4,8,16,32,48 week after 375 mg/m.sq of rituximab infusion 14 days apart premedicated with 80mg of methylprednisolone.

Results- at the end of 48 weeks 1st patient- 30 y old male Pre-treatment 4 week 8 week 16 week 32 week 48 week BASDAI 5.8 3.9 3.7 2.8 2.7 2.3 BASFI 6.5 6.4 5.2 4.8 4.2 2.1 BASMI 5.5 4.1 4.0 3.3 3.1 ESR/CRP 48/92 28/68 22/60 12/36 10/24 10/16 Global assessment score(ASDS-CRP) 3.4 3.2 2.6 2.4 2.0

Global assessment score(ASDS-CRP) 2nd patient 22y male Pre-treatment 4 week 8 week 16 week 32 week 48 week BASDAI 4.6 4.3 2.3 1.9 1.5 1.1 BASFI 5.5 5.2 4.2 3.9 2.8 BASMI 4.9 3.7 3.6 3.0 2.2 ESR/CRP 40/86 32/64 18/28 16/14 12/14 Global assessment score(ASDS-CRP) 3.8 2.0

MRI improvement in the 1st patient Before After

Literature Search Song et al. investigated the efficacy of rituximab in 20 AS patients who did not respond to treatment with TNF-alpha. The evaluation made at the end of 24 weeks showed that rituximab was not effective in patients who did not respond to TNF-alpha inhibitor before but was an effective treatment option for patients who were naive to TNF-alpha. French rheumatology society evaluated efficacy of rituximab in 26 patients of AS among 11 responded well though 8 were TNF-alpha inhibitor naive. I-H. Song, F. Heldmann, M. Rudwaleit Et Al., “Different Response To Rituximab In Tumor Necrosis Factor Blocker-Naïve Patients With Active Ankylosing Spondylitis And In Patients In Whom Tumor Necrosis Factor Blockers Have Failed: A Twenty-Fourweek Clinical Trial,” Arthritis And Rheumatism, Vol. 62, No. 5, Pp.1290–1297, 2010 G. Nocturne,M.Dougados, A. Constantin,C.Richez, J. Sellam, And A. Simon, “Lack Of Efficacy Of Rituximab In Spondyloarthropathies: Data Of 8 Patients Prospectively Followed In The French AIR (‘Auto-Immunity And Rituximab’) Registry,” Annals Of The Rheumatic Diseases, Vol. 68, Supplement 3, P. 626, 2009.

Advantages of Rituximab Dose adjusted to body-surface area. No such chances of latent tuberculosis re-activation. Only 2 doses are sufficient compared to periodic dosing of TNF-alpha inhibitors.

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