Evidence map›Paper›PMID 26137975›Full record

Trial reportArthritis & rheumatology (Hoboken, N.J.)2015

Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial.

R F van Vollenhoven, S Wax, Y Li, P P Tak

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00664521 (A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.), which is not on this map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
2.7field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00664521 phase2completednot on this map

A Randomized, Double-blind, Placebo Controlled, Multi-centre, Exploratory, Pilot, Phase II Trial of 150mg Atacicept Given Subcutaneously in Combination With Rituximab in Subjects With Rheumatoid Arthritis.

TypeinterventionalSponsorMerck KGaA, Darmstadt, GermanyRan2008 to 2010Enrolled27ConditionsRheumatoid ArthritisArmsRituximab, Atacicept, Placebo matched to atacicept
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 35 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 4 countries.

R F van VollenhovenKarolinska Institute, Stockholm, Sweden.
S WaxEMD Serono, Inc., Rockland, Massachusetts.
Y LiEMD Serono, Inc., Rockland, Massachusetts.
P P TakAcademic Medical Center and University of Amsterdam, Amsterdam, The Netherlands, University of Cambridge, Cambridge, UK, and GlaxoSmithKline, Stevenage, UK.
Ono Pharmaceutical (United States) · USKarolinska Institutet · SEUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo explore the safety and tolerability of atacicept in combination with rituximab in patients with active rheumatoid arthritis (RA) receiving rituximab re-treatment.

methodsIn this randomized, double-blind, placebo-controlled pilot trial, 2 infusions (1,000 mg per infusion) of intravenous rituximab, given 2 weeks apart, were followed by once-weekly subcutaneous injections of 150 mg atacicept or placebo for 25 weeks. Primary end points were the nature, incidence, and severity of adverse events (AEs). Secondary end points were the effects on peripheral blood B cells, disease activity biomarkers, and American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) response rates.

resultsEighteen patients were randomized to receive atacicept and 9 to receive placebo. AEs occurred in 17 atacicept-treated patients (94.4%) and in all 9 placebo-treated patients (100%). There were no infection-related serious adverse events. Hypersensitivity and injection site reactions were more common, and more patients withdrew due to AEs, in the atacicept group. Median reductions in Ig levels from baseline to week 32 were greater with atacicept (median change in IgG -31.2%, IgM -60.9%, and IgA -56.4%) than with placebo (median change in IgG -4.4%, IgM -15.9%, and IgA -8.2%). Peripheral B cell numbers remained low in all patients after rituximab-mediated B cell depletion, limiting comparison of time to recovery between treatment groups. There were no between-group differences in ACR20, ACR50, and ACR70 response rates.

conclusionIn this exploratory trial, atacicept in combination with rituximab showed no new safety issues. Peripheral B cell counts remained too low to determine whether atacicept delayed B cell re-expansion following rituximab-mediated depletion. Despite clear biologic effects, adding atacicept to rituximab in patients with active RA was not associated with clinical benefit.

Indexed as

AgedAntirheumatic AgentsArthritis, RheumatoidDouble-Blind MethodDrug Therapy, CombinationFemaleHumansMaleMiddle AgedRecombinant Fusion ProteinsRituximabTreatment OutcomeAntirheumatic AgentsRecombinant Fusion ProteinsRituximabTACI receptor-IgG Fc fragment fusion protein

Identifiers

PMID26137975
PMCPMC5057363
OpenAlexW2166244826

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.