6 ADRs, 2 LOE. 2 ADRs, 4 LOE. Ineffectiveness 24 ADRs 7, 1 pt for convenience. 48% had antibodies against Infliximab at baseline

Transcription

1 Summary of Published Switch data Table 1. Information Patients Switch from (n) Reason for switch Switch to: (n) Results Numbers Presse Med (1) 14 Infliximab (8) (6) 6 ADRs, 2 LOE 2 ADRs, 4 LOE (8) Infliximab (6) Benefit in 5 pts, 2 did not respond and 1 withdrew Benefit in 3 pts, 2 did not respond, 1 withdrew for ADR Joint Bone and Spine Editorial (2) Ann of Rheum Dis 2003 (3) STURE database Journal of Rheum 2004 (4) Journal of Rheum 2004 (5) Ang HT et al Journal of Rheum 2003 (6) 32 (13) Infliximab (19) 31 (18) Ineffectiveness 24 ADRs 7, 1 pt for convenience 2 ADRs, 14 LOE 2 unknown Infliximab (13) 11 ADRs 2 unknown 25 Infliximab (25) 19 LOE, 3 ADRs and 3 others 48% had antibodies against Infliximab at baseline 20 (20) 17 LOE, 1 due to etanercept not being available, 2 for safety concerns 23 Infliximab (24) LOE and ADRs (5) Infliximab (13) (19) Infliximab (18, 15/18 + MTX) (13) (25) Infliximab + Leflunomide (20) Infliximab Excellent response in 8 of the 14 75% classified as responders from the combined groups Better efficacy with 2 nd line agent At least equal efficacy with 2 nd line agent 55% of the patients switched achieved a ACR20 response at 6 weeks which increased to 64% in 12 week Clinically meaningful improvements in functional status were experienced on 37% of pts at 6 weeks and 59% at week 12. No pts were withdrawn due to ADRs or LOE. Previous LOE with etanercept did not predict a LOE with this combination Not fully reported Joint Count 69% of patients remained on 2 nd treatment

2 Information Arthritis & Rheumatism 2005 (7) Journal of Rheumatology 2003 (8) Rheumatology 2005 (9) Patients Numbers 25 Switch from (n) Reason for switch Switch to: (n) Results Infliximab (25) N= 10 type A no CPR or ACR 20 response N= 15 type B initial CRP reduction then rise 29 (24) Infliximab (5) 26 Infliximab (23) (5) Anakinra (1) Non responders or initial response by CRP and ACR 20 at week 12 of Infliximab treatment 12 LOE, 10 ADR and 2 other. 2 LOE, 3 ADR 21 primary or secondary LOE, 6 ADR and 2 other Supply issues and wishing to self administer (25) Infliximab (24) (5) (26) Failure to suppress CRP in Infliximab patients at week 2 identified the majority of patients who had not responded by week 12. CRP reduced in these patients once treated with etanercept Response after switch Type A, achieved 66% ACR20, 66% ACR50 and 33% ACR70 Type B, achieved 71% ACR20, 57 ACR50 and 14% ACR70 Failure to respond to Infliximab did not predict a failure to respond to etanercept After switch 31% patients no longer on TNF therapy 69% were maintained. No correlation between the responses to the 2 agents with regards to joint count and CRP. Correlation with the occurrence of anaemia with use of either product Fifty four (77%) pts achieved a EULAR response 18 (26%) had a good response and 36 (51%) a moderate response. 13 (19%) were in remission. The mean DAS28 improvement was 2.1 after a mean of 7.3. The mean HAQ improved A clinically significant decrease in HAQ of greater than 0.22 occurred in 66% of pts. 11 (15%) pts stopped adalimumab for treatment failure and 5 (7%) for ADRs

3 Information Ann Rheum Dis 2006 (10) Ann Rheum Dis 2004 (11) Joint Bone and Spine Editorial (12) Patients Numbers Switch from (n) Reason for switch Switch to: (n) Results 28 Infliximab (28) 9 LOE, 16 ADRs, Patients were treated for 1 year and were and 3 lost to follow (24) matched and compared with 25 patients who up received adalimumab who had not previously used Infliximab. After 1 year clinical responses were similar in both groups. ACR20 responces were achieved in 18/24 (75%) switchers and by 19/25 (76%) in the adalimumab control group. Four switchers discontinued the study 2 from LOE and 2 from ADRs, while 3 of the contol patients discontinued 1 for LOE and 2 for ADRs. 12 Infliximab (12) Switched treatment (12) After 6 10/12 (85%) had a good (2 for reduced efficacy patients) or moderate (8 patients) therapeutic response according to EULAR criteria. DAS28 improved from a mean (SD) 5.63 (1.1) to 4.30 (0.8) (p=0.019) and the % of pts with DAS28>5.5 was reduced from 75% at the end of Infliximab to 8% after 6 on 18 Failed etanercept or both etanercept and Infliximab LOE and ADRs (18) etanercept (p=0.009) Of 10 patient who had not failed on etanercept and Infliximab 5 responded to adalimumab and 5 did not. Three patients did not respond to any of the 3 TNFα agents. Of the 8 patients who had only failed etanercept 5 patients (1 from LOE and 4 ADRs) responded to adalimumab and 3 did not. Ten of the 18 patients benefited from a switch to adalimumab.

4 Posters and Abstracts Table 2. Information Patient Numbers Switch From (n) EULAR Infliximab (2) AB0121 (13) (1) EULAR 2003 THU0223 (14) THU0226 (15) Reason for switch 1LOE, 1 ADR 1 LOE 25 Infliximab (25) 72% LOE, 16% ADRs Switched to (n) (2) Infliximab (1) (25) Results from baseline at switch Of the patients switched to etanercept ACR20 response was achieved in 1 at week 14 and ARC 50 in 1 at week 22. The Infliximab patient achieved a ACR50 response at week 46. The Mean HAQ decreased from 1.5 at baseline to 1.1 at 12 weeks, indicating a decrease in disability. Improved functioning in pts where Infliximab had failed. ACR responses in 24 pts, ACR 2004 Poster 374(16) ACR 2004 number 968 (17) DANBIO, Danish registry 12 Infliximab (+ MTX 8 pts) Leflunomide 2 pts. Mean RX time 15 Lack of efficacy. Pts switched due to ADRs were excluded 116 Not recorded 29 LOE, 28 ADRs and 59 reason not reported (n=12) Not recorded ACR20 week 6-50%. Week % ACR50 week 6 25%. Week % ACR70 Week % week % Mean CRP at baseline 17.1 dropped to 11.4 at 12 weeks DAS28 Baseline 5.63, reduced to 4.30 at 6 month (p=0.019), at 1 year 4.58 (p=0.015) EULAR response at 6 83% and 50% at one year Mean DAS at baseline for all patients was DAS improvement at 1.5 : 1.59, after 3 : 1.56, after and after 12 : Pts demonstrated statistically significant DAS improvement regardless of the reason for switching. Pts who switched for LOE had a significantly better response to their 2 nd biologic at 6 than their 1 st biologic. Pts who switched for ADRs achieved similar efficacy results as was achieved with their 1 st biologic

5 ACR 2004 number 990 (18) 155 Infliximab (n=83) (n=72) LOE (n=75) Infliximab (n=67) Infliximab to etanercept results n=75 Baseline mean At 6 Mean change HAQ Pain VAS % of pts achieved a macr20 at % of patients had HAQ 0.5 at 6 to Infliximab results n=67 Baseline mean At 6 Mean change HAQ Pain VAS % of pts achieved a macr20 at 6 9.0% of patients had HAQ 0.5 at 6 At baseline all pt characteristics were similar with the exception of median duration of RA 3.21 yrs in the Infliximab to etanercept group compared with 9.36yrs in the etanercept to Infliximab group

6 Information EULAR 2004 number FR10180 (19) ACR 2005 Number 882 (20) Patient Switch Numbers From (n) 396 Infliximab (272) (210) Anakinra (21) 103 Infliximab (57%) Reason for switch 184 LOE, 183 ADRs 308 pts with RA Primary non responders (PNR)18% Secondary non responders (SNR) 29% and toxicity 10% Switched to (n) (294) Results from baseline at switch Recurrence of previous ADRs was rare. Treatment response was achieved in 2/3 of pts but the outcome for individual pts needs further evaluation Included pts with RA, AS, JIA, PsA, crohns and other rheumatic diseases At week 12 the PNRs, 36% achieved a moderate and 7% good EULAR response, with a mean DAS28 reduction of 1.3 (from 6.7) From the SNR 64% achieved a moderate and 7% good EULAR response, with a mean DAS28 reduction of 1.4 (from 6.3). SNR responded better to adalimumab. No reports for 38% of Infliximab patients ACR 2005 number 294 (21) 463 Infliximab (356) (107) Loss or LOE 270, ADR 86. Loss or LOE 76, ADR 31. (819) Efficacy measured at 12 weeks. Eight patients discontinued adalimumab due to ADRs. Of the 14 patients treated unsuccessfully with both infliximab and etanercept 3 had an ACR response of ACR 50. The response was better in patients naïve to TNFs but prior treatment did indicate greater disease involvement. ACR 2005 number 1488(22) 22 Infliximab (15) (7) 68% due to LOE 32% ARDs (22) 50mg once weekly Efficacy measured at 24 weeks. One patient withdrew for ADR. ACR20 response in 12/21 (57%) ACR50 in 5/21 (24%) ACR70 in 2/21 (9.5%) and 2/21 failed to achieve a clinical improvement. Mean DAS28 declined from 5.30 to 2.87 (p<0.001). represented a good therapeutic response in pts who were resistant or intolerant to other anti- TNFα agents.

7 ACR 2005 number 857 (23) 942 Infliximab 496 (62%)LOE and 446 (47%) ADRs Infliximab The non-response rate was 16% in those who had not responded to the first agent and 9% in those who had experienced an ADR to the first. Cumulative ADRs was 23%. If the reason for switch was LOE there was no increased incidence of ADR, but if the primary reason for switch was ADR then the likelihood of recurrence to ADR was 2-3 fold. Following failure to first agent patients may benefit from switch to a second agent but physicians should consider risks. EULAR 2005 number SAT 0182 (24) EULAR 2005 number SAT0111 (25) Atzeni F et al EULAR 2006 (26) 191 switches pts twice 3 pts three times, infliximab and adalimumab 15 Infliximab followed by etanercept LOE, Toxicity Dr preference 23 (61%) LOE 13 (34%) ADRs 2 (5%) compliance Non response or adverse events for first switch, switch to ALB on basis of DAS28>5.1, infliximab and adalimumab. Infliximab, etanercept, adalimumab, anakinra and rituximab Toxicity most common reason for switch. Switching agents did result in clinical improvement in DAS and other individual outcomes At 12 weeks 27 (71%) showed response, 20 showed a sustained response after a mean duration of 11. Ten pts (26%) did not respond to second biologic, 1 stopped due to ADR. The mean disease duration for responders was 11.4 yrs compared to 20.9 for nonresponders. The mean reduction in DAS28 scores from baseline to 3 were: Biologic 1, 7.3 to 5.7, biologic 2, 6.2 to 5.4, biologic 3, 7.4 to 5.9 and biologic 4, 7.2 to 5.3. Overall 30 (80%) successfully switched with good clinical effect. Better responses seen in those with shorter disease duration

8 Information Naumann et al. EULAR 2006 (27) ABO190 Kristensen et al. EULAR 2006 FRI 0135 (28) Patients Numbers Switch from (n) Reason for switch Switch to: (n) Results 41 Any anti TNF Severe adverse Infliximab, DAS alpha event (7) and ineffectiveness (22) incompliance (2) st /2 nd and 3 rd line failures Any anti TNF alpha Any (239), (165) Remaining on Therapy and ACR 20 response rates Adhere nce to therapy ETN naïve Previous ETN ADA naïve Previous ADA ACR 20 ETN naïve Previous ETN ADA naïve Previous ADA no data no data * no data no data 33** no data no data

9 1. Brocq et al. Presse Med. November 23;31 pg Combe. B et al. Switching between anti -TNFα agents: what is the evidence? Joint Bone and Spine (71) van Vollenhoven et al. Treatment with Infliximab (Remicade) when etanercept (Enbrel) has failed or vice versa: data from the STURE registry showing that switching tumour necrosis factor α blockers can make sense. Annals of Rheumatic Diseases (62) Boulos et al. Clinical Outcomes of patients with rheumatoid arthritis after switching from Infliximab to. Journal of Rheumatology (31) Hasen et al. The Efficacy of switching from etanercept to Infliximab in Patients with Rheumatoid Arthritis. Journal of Rheumatology (31) Ang HT, Helfgott S. Do the clinical responses and complications following etanercept or infliximab predict similar outcomes with other tumour necrosis factor alpha antagonists in patients with rheumatoid arthritis? J Rheumatology 2003; 30: Buch.M. et al C-Reactive Protein as a predictor of Infliximab treatment outcome in patients with Rheumatoid Arthritis. Arthritis and Rheumatism (52) Herbert T. et al Do the Clinical Responses and Complications following etanercept or Infliximab therapy predict similar outcomes with the other Tumor Necrosis Factor-α Antagonists in patients with Rheumatoid Arthritis. Journal of Rheumatology. (30) Bennett. A.N et al in Clinical practice. Outcome of 70 rheumatoid arthritis patients, including comparison of patients with and without previous anti- TNF exposure. Rheumatology (44) Nikas S.N. et al. Efficacy and Safety of switching from Infliximab to adalimumab: a comparative controlled study. Annuals of Rheumatic Diseases. (66) Gomez J.A. et al is effective in patients with Rheumatoid Arthritis with no response to Infliximab therapy. Annual of Rheumatic Diseases. (63) Brocq.O. et al in rheumatoid arthritis after failing Infliximab and/ or etanercept therapy: experience with 18 patients. Joint Bone and Spine, (74) Erra. A. et al Experience in the switch from Infliximab to etanercept or Vice versa, in Rheumatoid arthritis patients. EULAR (AB0121) 14. Haraoui.P. et al The Canadian biologics observational switchover survey (BOSS): Functional status of patients with rheumatoid arthritis after switching from Infliximab to etanercept therapy. EULAR. THU Haraoui.P. et al The Canadian biologics observational switchover survey (BOSS): switching from Infliximab to etanercept leads to successful treatment of rheumatoid arthritis. EULAR. THU Gomez. J. One-year efficacy of in rheumatoid arthritis patients who previously failed Infliximab. Poster 374/ 373. ACR 2004

10 17. Hjarden E. Do patients benefit from switching to a second Biologic when the first is withdrawn due to lack of efficacy or Adverse Event? ACR 2004 number Keystone E.C. Switching Anti-TNF therapy: Real-World outcomes of patients with rheumatoid arthritis who failed either Infliximab or treatment and switched to another TNF inhibitor. ACR 2004 number Feltelius. K. et al. Safety and efficacy of adalimumab in arthritis patients previously treated with another biologic agent. EULAR presentation number FR Buch. M. Type of previous Infliximab non-response in Rheumatoid arthritis determines subsequent response to. number 882. ACR Bombardieri. S. is effective in treating patients with Rheumatoid Arthritis who previously failed etanercept and/or Infliximab in real-life clinical setting. number 294. ACR Cantini. F. Switching from infliximab or adalimumab to etanercept 50mg once weekly in resistant or intolerant patients with Rheumatoid arthritis: 24 week results. number ACR Kimme. L. et al Influcence of response and adverse event rates to a 1 st anti- TNFα agent on the outcome from switching to a 2 nd agent: Results from British Society of Rheumatology Biologics Registry. number 857. ACR Kafka. S.P. et al. Discontinuing or switching TNF antagonists in patients with rheumatoid arthritis: Data collected from the Corrona database. number SAT0182. EULAR Turner. L. et al. Biologics in rheumatoid arthritis switching is effective. number SAT0111. EULAR Atzeni F, Sarzi-Puttini P, Antivalle M, Turiel M, Carrabba M. in severe rheumatoid arthritis after failure of two anti-tnf agents: a prospective 1- year follow-up study of 15 patients. ABO168. EULAR Naumann L, Detert J, Buttgereit F, Burmester G. A second anti-tnfa therapy after treatment failure of the first anti-tnfa therapy results in a significant decrease of concomitant glucocorticoid treatment in patients with rheumatoid arthritis. EULAR ABO Kristensen LE, Saxne T, Geborek P. Switching between anti-tnf therapies does not affect level of adherence to therapy in rheumatoid arthritis but response rates seem to decline. EULAR FRI 0135