Landewe R, Strand V, truck der Heijde D. From inhibition of radiographic progression to maintaining structural integrity: a methodological framework for radiographic progression in rheumatoid arthritis and psoriatic arthritis clinical trials. week 100. Assessments included American College of Rheumatology 20%, 50%, 70% (ACR20, ACR50, ACR70) response criteria, 28\joint count disease activity score using the C\reactive protein level (DAS28\CRP), physical function and quality of life measures, and changes in the modified Sharp/van der Heijde scores (SHS). Safety was monitored through week 112. Results In total, 486 patients (82.1%) continued treatment through week 100, and 68.1%, 43.8%, and 23.5% had an ACR20/50/70 response, respectively, at week 100. Clinical response and improvements in physical function and quality of life were generally maintained from week 24 through 2 years. Mean change from baseline to week 100 in SHS score was 0.74 in Group 1 and 2.10 in Group 2 (colitis at week 106. Laboratory abnormalities Among all golimumab\treated patients who did not receive TB prophylaxis and who had a normal (i.e.,??ULN) baseline alanine aminotransferase (ALT) level, PAPA1 45.4% (n?=?204 of 449) had at least 1 increased ( ?ULN) postbaseline value through week 112. Of these patients, 186 had an increase in ALT 3 times the ULN, and no patient had an increase in ALT 8?times the ULN. Among golimumab\treated patients who received TB prophylaxis and had a normal baseline ALT level, 44.4% (n?=?36 of 81) had at least 1 postbaseline increase in ALT through week 112. Twenty\eight of these patients had an increase in ALT 3 times the ULN, and 3 patients had an increase 8 times the ULN. None of the increases in ALT was associated with an increase in bilirubin, infectious hepatitis, or any clinical symptomatology consistent with hepatic failure. All of the cases of increased ALT improved with modifications in treatment (mostly MTX and/or anti\TB medications; few with changes to golimumab), and no long\term toxicity was observed. One patient with an ALT level 8 times ULN was discontinued from the trial. Antibodies to golimumab Among golimumab\treated patients with appropriate serum samples (i.e., 1 sample after receiving golimumab), 3.0% (n?=?13 of 440) tested positive for antibodies to golimumab through week 24 3 and 4.6% (n?=?26 of 560) tested positive through week 52 3. Consistent with these findings, a small number JNJ-10229570 of patients developed antibodies to golimumab through week 100 (6.7%, [n?=?37 of 553]). Among the 37 patients who were positive for antibodies to golimumab at week 100, 86.5% were positive for neutralizing antibodies, and neutralizing, 3 patients (8.1%) had an infusion reaction, with 1 patient (2.7%) discontinuing the study agent as a result. Of the 516 patients who were negative for antibodies to golimumab, 22 (4.3%) had infusion reactions, none leading to discontinuation. DISCUSSION The multicenter, randomized, placebo\controlled GO\FURTHER trial evaluated the safety and efficacy of IV golimumab 2mg/kg plus MTX through 112 weeks in patients with RA despite prior MTX therapy. Golimumab\treated patients had significantly greater improvements in the signs and symptoms of RA through week 24 when JNJ-10229570 compared with placebo, with some patients experiencing a rapid onset of response as early as 2 weeks after initiating golimumab therapy JNJ-10229570 1, and efficacy was maintained through 1 year 3. Results through week 100 of the GO\FURTHER trial demonstrate that the observed clinical response to IV golimumab 2mg/kg plus MTX was sustained through 2 years of treatment. Of JNJ-10229570 the 592 patients who received treatment, approximately 82% completed golimumab therapy through week 100. The rate of discontinuation due to lack of efficacy among patients randomized to golimumab was relatively low (1.8%). Among all patients, 68.1%, 43.8%, and 23.5% had an ACR20, ACR50, and ACR70 response at week 100, respectively, and 81.9% had either a moderate or good DAS28\CRP response. In addition, the majority of patients who had an ACR20, ACR50, ACR70, or DAS28\CRP response at week 52 maintained that response at week 100. Taken together with earlier results 1, 3, the GO\FURTHER trial demonstrated that clinical response to IV golimumab 2mg/kg plus MTX can occur as early as week 2, and once achieved, is often sustained through 1 and 2 years for patients with active RA who previously had an insufficient response with MTX monotherapy. Improvements in health\related quality of life, fatigue, and the impact of disease on productivity that were observed among golimumab plus MTX\treated patients at week 24 16 were also maintained through 1 and 2 years in the GO\FURTHER trial. Patients treated with IV golimumab plus MTX from baseline had significantly less radiographic progression from baseline to weeks 24, 52, and 100 when compared with patients who had initially received placebo plus MTX. Evaluation of the radiographic component scores indicated that the increases from baseline among patients in Group 2 were largely due to changes in joint space narrowing rather than erosions. It should be noted, however, that at all time points, including week 100,.