Rituximab Is an Attractive Proposition to Treat Difficult Active RA in Indian (Asia) Patients: Initial Results of a Non Commercial Initiative Using an Initial Regimen of Two 500 Mg Infusions (fortnightly) and a Third 500 Mg Infusion at 6 Weeks in Case of Inadequate Response(ACR 50)

Arvind Chopra¹, KIRAN ADAM², NACHIKET KULKARNI³, Anuradha Venugopalan⁴, Toktam Kainifard⁵ and Manjit Saluja⁶, ¹Center for Rheumatic Diseases, Pune, India, Pune, India, ²Rheumatology physician, PUNE, India, ³MD, DNB, PUNE, India, ⁴Rheumatology, R & D, Lab, Center for Rheumatic Diseases, Pune, India, ⁵Rheumatology, Consultant research and Dietitian, Pune, India, ⁶Rheumatology, Co-ordinator Research, Pune, India

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: B cell targeting, observation, rheumatoid arthritis (RA) and rituximab

Session Information

Date: Tuesday, November 7, 2017

Session Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy Poster III: Efficacy and Safety of Originator Biologics and Biosimilars

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Considering the huge burden of RA in India, the use of biologic DMARDs is miniscule. The major deterrents are cost, poor awareness and few rheumatologists. Despite an inherent appeal, Rituximab (RTX) is yet to find favour.Encouraged by a generous donation of Rituximab (Ristovos™/ RTX) vials, we designed a protocol driven observational study to determine the response to RTX in RA and optimize outcome. We present initial results. The study is ongoing.

Methods: 60 consenting patients (ACR 1987 classified, 80% women, mean age 45.2 years,100% seropositive RF/anti CCP, 92% erosive, 35% deformities) with active severe RA (mean disease duration 92 months, mean DAS 28 ESR 6.5) despite prolonged methotrexate (mean dose 18.5 mg weekly) and often steroid intake (8.5 mg daily)were enrolled to receive RTX (2 infusions, 500 mg each, fortnightly)in a community rheumatology centre; standard screening included that for TB.We use ACR recommended 68/66 joint count and efficacy measures in routine practise; validated Indian HAQ version. Clinical status and background medication (especially methotrexate and steroids) was monitored at week 6, 12, 24 and 36 as per protocol. 31 Patients failed ACR 50 (primary response)at week 6 and were randomized into 2 arms [500 mg RTX infusion (third)plus 120 mg injectable methylprednisolone (M-Pred) in 14 patients or only 120 mg M-Pred in 17 patients). At subsequent evaluations, all ACR 50 non-respondents received single 120 mg M-Pred. Comprehensive laboratory work up included CD 19 cell count (Beckman Coulter FC 500). Standard statistical analysis was performed; significant p < 0.05. 54 patients completed 24 weeks and 50 patients completed 36 weeks.

Results: Patients improved significantly in joint counts, pain VAS and HAQ by week 24& 36 (p<0.05), mean DAS 28 reduced to 3.1 (low disease activity). General Health improved from 5.2 to 7.3 [mean VAS, 0 (poor) to 10 cm(optimum) .Patients with ACR 50 response at week 6 had least CD 19 count and were likely to maintain response by week 34. Patients receiving 3 infusions had the lowest CD 19 count at week 12. Table shows (percent patients) ACR 50& 70 response. The additional RTX infusion did not seem to confer any obvious benefit.Two patients withdrew soon after the initial infusions (1 developed severe febrile cytopenia, anaemia and mucositis). None of the patients completing 36 weeks withdrew due to AE, albeit mild (dyspepsia, skin rash, mucositis, upper respiratory infections and headaches).We admit several confounders and limitations.

Conclusion: In this true to life Indian study, patients with difficult RA were treated with a relatively lower dose Rituximab but showed a significant sustained improvement for least 36 weeks. The ACR 50 and 70 response was strikingly encouraging. The role of Rituximab in certain subjects (RA) may be profound. We beseech an early validation study by the innovator.

Patient Category / Evaluation visit (weeks)	R II (n=23)	NR II (n=17)	NR III (n=14)	TOTAL (n=54)
Week 6	*	*	*	43
Week 12	83 (43)	71 (31)	71 (14)	80 (35)
Week 24	80 (38)	65 (6)	64 (14)	76 (37)
Week 36	78 (47)	63 (20)	86 (14)	80 (36)
*Patients were classified as per ACR 50 response and Rituximab infusion regimen at week 6; R II: ACR 50 respondent at week 6 after two infusion of Rituximab (RTX) at baseline; NR II: ACR 50 Non-respondent at week 6 after two infusion of RTX at baseline (randomized); NR III: ACR50 Non- respondent at week 6 after two infusion of Rituximab (RTX) at baseline and randomized to receive third infusion; ACR 70 response shown in parenthesis above; n: number of patients of RA in study

Disclosure: A. Chopra, None; K. ADAM, None; N. KULKARNI, None; A. Venugopalan, None; T. Kainifard, None; M. Saluja, None.

To cite this abstract in AMA style:

Chopra A, ADAM K, KULKARNI N, Venugopalan A, Kainifard T, Saluja M. Rituximab Is an Attractive Proposition to Treat Difficult Active RA in Indian (Asia) Patients: Initial Results of a Non Commercial Initiative Using an Initial Regimen of Two 500 Mg Infusions (fortnightly) and a Third 500 Mg Infusion at 6 Weeks in Case of Inadequate Response(ACR 50) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/rituximab-is-an-attractive-proposition-to-treat-difficult-active-ra-in-indian-asia-patients-initial-results-of-a-non-commercial-initiative-using-an-initial-regimen-of-two-500-mg-infusions-fortnigh/. Accessed October 22, 2020.

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