Association of baseline C-reactive protein and prior anti-tumor necrosis factor therapy with need for weekly dosing during maintenance therapy with adalimumab in patients with moderate to severe Crohn’s disease

Abstract

Objective:

A post hoc analysis of data from the adalimumab Crohn’s disease (CD) maintenance trial (CHARM, NCT00077779), examining the relationship between adalimumab dosing and maintenance of remission and response in subgroups stratified by previous anti-TNF use and baseline CRP.

Methods:

All patients received open-label induction (adalimumab: 80 mg, week [wk] 0; 40 mg, wk 2). At wk 4, all patients were randomized to double-blind maintenance adalimumab (40 mg weekly or every other week [eow]) or placebo for 52 weeks. In this analysis, clinical remission (CDAI <150) and clinical response (CR-100) at wk 26 and wk 56 by baseline CRP (high: ≥10 mg/L, or low: <10 mg/L) and prior anti-TNF use were determined for patients with CR-70 at wk 4.

Results:

Of 498 patients in this analysis, 260 (52.2%) were anti-TNF-naïve. For anti-TNF-naïve patients, the wk 56 remission rates in the adalimumab groups were significantly greater than placebo (P < 0.05) for both high and low CRP cohorts, with no statistically significant differences between remission rates with eow and weekly dosing within each CRP cohort (high: 52.8% eow, 53.5% weekly; low: 34.7% eow, 41.9% weekly). For anti-TNF-exposed patients, wk 56 remission rates were higher than placebo with both eow and weekly dosing within each cohort; weekly dosing in the high CRP cohort and eow dosing in the low CRP cohort achieved statistical significance (P < 0.05). In the high CRP cohort, remission rate with weekly dosing (46.9%) was statistically significantly greater compared with eow dosing (22.5%). There were no significant differences between eow (23.1%) and weekly (37.0%) dosing in the low CRP group. For all subgroups, clinical remission (wk 26) and clinical response (wk 26 and wk 56) patterns were similar to those observed for wk 56 remission.

Conclusions:

These subgroup analyses suggest that in patients with moderately to severely active CD, weekly dosing may be most effective in the anti-TNF-experienced patients with elevated CRP at baseline.

Keywords::

• Adalimumab
• Clinical remission
• C-reactive protein
• Crohn’s disease
• Dose

Transparency

Declaration of funding

This study was funded by AbbVie Inc. AbbVie was responsible for the study design, research, analysis, data collection, interpretation of data, and writing, review, and approval of the publication. All authors had access to the data, reviewed each draft of the manuscript, and approved the final content.

Declaration of financial/other relationships

W.J.S. – Consultant: AbbVie, ActoGeniX NV, AGI Therapeutics Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-Pharma BV, Anaphore, Astellas Pharma, Athersys Inc., Atlantic Healthcare Limited, Axcan Pharma (now Aptalis), BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical Research Inc., Elan Pharmaceuticals, EnGene Inc., Eli Lilly, Enteromedics, Exagen Diagnostics Inc., Ferring Pharmaceuticals, Flexion Therapeutics Inc., Funxional Therapeutics Limited, Genzyme Corporation, Genentech (now Roche), Gilead Sciences, Given Imaging, Glaxo Smith Kline, Human Genome Sciences, Ironwood Pharmaceuticals (previously Microbia Inc.), Janssen (previously Centocor), KaloBios Pharmaceuticals Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals (previously Alaven Pharmaceuticals), Merck Research Laboratories, MerckSerono, Millennium Pharmaceuticals (subsequently merged with Takeda), Nisshin Kyorin Pharmaceuticals Co. Ltd, Novo Nordisk A/S, NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics Inc., PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis Technologies Inc., Receptos, Relypsa Inc., Salient Pharmaceuticals, Salix Pharmaceuticals Inc., Santarus, Schering Plough Corporation (acquired by Merck), Shire Pharmaceuticals, Sigmoid Pharma Limited, Sirtris Pharmaceuticals Inc. (a GSK company), S.L.A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma AG (acquired by Zeria Pharmaceutical Co. Ltd), TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics Limited (VBL), Warner Chilcott UK Limited, Wyeth (now Pfizer). Speakers fees: AbbVie, Bristol Meyers Squibb, and Janssen (previously Centocor). Financial support for research: AbbVie, Bristol Meyers Squibb, Genentech, Glaxo Smith Kline, Janssen (previously Centocor), Millennium Pharmaceuticals (now Takeda), Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals, and UCB Pharma. J.-F.C. – Consultant: AbbVie, ActoGeniX NV, Albireo Pharma, Astra Zeneca, Bayer Schering Pharma, Biogen Idec, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Janssen (previously Centocor), Chemocentryx, Cosmo Technologies, Danone France, Elan, Genentech, Giuliani, Given Imaging, GlaxoSmithKline, Merck, Millennium, NeoVacs, Ocerra (previously named Renovia), Otsuka American, PDL Biopharma (previously named Protein Design Labs), Pfizer, Ribo Vacs Biotech, Schering-Plough, Shire, Synta, Teva and Petah Tikva, Therakos, UCB (previously named Celltech Therapeutics). Speakers fees: AbbVie, Astra Zeneca, Janssen (previously Centocor), Elan, Falk, Ferring, Given Imaging, Otsuka American, PDL, Schering-Plough, Shire and UCB. Financial support for research: Astra-Zeneca, Danisco, Danone, Dysphar, Ferring, Giuliani, Lesaffre, Mapi Naxis, Ocerra Therapeutics (previously named Renovia), Roquette, Schering-Plough and UCB. Shareholder: Intestinal Biotech Development. G.D’H. – Consultant: AbbVie, Actogenix, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Jansen Biologics, Millenium Pharmaceuticals, MSD, Novonordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB; Research grants from AbbVie, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma, Photopill. Speakers fees: AbbVie, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Otsuka, Shire and Vifor Pharma. Shareholder: EnGene Inc. S.E.P. – Consultant: Abbott Immunology, Biomodels Inc., Bristol-Meyers Squibb, Baxter Pharmaceuticals, Calcimedica Inc., Drais Pharmaceuticals, Elan Pharmaceuticals, enGene Inc., Genentech Inc., Human Genome Sciences, Janssen Biotechnology, Novartis, Novo Nordisk, NPS Pharmaceuticals, Pfizer, Prometheus Laboratories, Protagonist Therapeutics Inc., Receptos, Shire, Synergy Pharmaceuticals, Takeda Pharmaceuticals, Vertex Pharmaceuticals, Therakos Inc., TransTech Pharmaceuticals, UCB Pharmaceuticals. Speakers fees: Participated in multi-sponsored CME symposia that may have been funded partially by Janssen Biotechnology, AbbVie, Salix Pharmaceuticals, and/or UCB Pharmaceuticals. Financial support for research: Janssen Biotechnology, AbbVie, Prometheus Laboratories. Shareholder: EnGene Inc. and Protagonist Therapeutics Inc. J.P. – Consultant: AbbVie, Bristol-Myers Squibb, Cellerix, Genentech, Merck Sharp & Dohme, Pfizer, Schering-Plough, and UCB Laboratories. Speakers fees: AbbVie, Ferring, Merk Sharp & Dohme, Otsuka, Schering-Plough, Shire and UCB Laboratories. Financial support for research: AbbVie and Schering-Plough. A.M.R., Q.Z., M.C., and R.B.T. are employees of AbbVie and may hold AbbVie stock and/or options. P.F.P. is a former AbbVie employee and may hold AbbVie stock.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Laurinda Cooker PhD of AbbVie for assistance in writing the first draft and in preparation of the manuscript.

Portions of this manuscript were presented at the 19th United European Gastroenterology Week, 2011, and at Digestive Disease Week, 2012.